Diabetes and the gut. Scarpello J H,Sladen G E Gut 10.1136/gut.19.12.1153
    Disorders of gastrointestinal motility associated with diabetes mellitus. Feldman M,Schiller L R Annals of internal medicine Gastrointestinal symptoms such as vomiting, constipation, diarrhea, and fecal incontinence occur frequently in patients with diabetes mellitus. In a survey of 136 diabetic outpatients, 76% had one or more gastrointestinal symptoms, the commonest symptom being constipation (found in 60%). In many cases these symptoms are thought to be due to abnormal gastrointestinal motility that, in turn, may be a manifestation of diabetic autonomic neuropathy involving the gastrointestinal tract. The pathophysiology of these gastrointestinal symptoms, clarified in recent studies, and the clinical features and treatment of these problems in diabetic patients are reviewed. 10.7326/0003-4819-98-3-378
    The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation. Hiippala Kaisa,Jouhten Hanne,Ronkainen Aki,Hartikainen Anna,Kainulainen Veera,Jalanka Jonna,Satokari Reetta Nutrients The intestinal microbiota, composed of pro- and anti-inflammatory microbes, has an essential role in maintaining gut homeostasis and functionality. An overly hygienic lifestyle, consumption of processed and fiber-poor foods, or antibiotics are major factors modulating the microbiota and possibly leading to longstanding dysbiosis. Dysbiotic microbiota is characterized to have altered composition, reduced diversity and stability, as well as increased levels of lipopolysaccharide-containing, proinflammatory bacteria. Specific commensal species as novel probiotics, so-called next-generation probiotics, could restore the intestinal health by means of attenuating inflammation and strengthening the epithelial barrier. In this review we summarize the latest findings considering the beneficial effects of the promising commensals across all major intestinal phyla. These include the already well-known bifidobacteria, which use extracellular structures or secreted substances to promote intestinal health. , , and metabolize dietary fibers as major short-chain fatty acid producers providing energy sources for enterocytes and achieving anti-inflammatory effects in the gut. exerts beneficial action in metabolic diseases and fortifies the barrier function. The health-promoting effects of species are relatively recently discovered with the findings of excreted immunomodulatory molecules. These promising, unconventional probiotics could be a part of biotherapeutic strategies in the future. 10.3390/nu10080988
    [Gut microbiota and immune crosstalk in metabolic disease]. Burcelin Rémy Biologie aujourd'hui The aim of the review is to discuss about the role played by the defence crosstalk between the gut microbiota and the intestinal immune system, in the development of metabolic disease focusing on obesity and diabetes. Starting from physiological and pathological stand points and based on the latest published data, this review is addressing how the concept of the hologenome theory of evolution can drive the fate of metabolic disease. The notion of "metabolic infection" to explain the "metabolic inflammation" is discussed. This imply comments about the process of bacterial translocation and impaired intestinal immune defense against commensals. Eventually this review sets the soil for personalized medicine. The monthly increase in the number of publications on the gut microbiota to intestinal immune defense and the control of metabolism demonstrate the importance of this field of investigation. The notion of commensal as "self or non-self" has to be reevaluated in the light of the current data. Furthermore, data demonstrate the major role played by short chain fatty acids, secondary bile acids, LPS, peptidoglycans, indole derivatives, and other bacteria-related molecules on the shaping of cells involved in the intestinal protection against commensals is now becoming a central player in the incidence of metabolic diseases. The literature demonstrates that the onset of metabolic diseases and some specific co-morbidities can be explained by a gut microbiota to intestinal immune system crosstalk. Therefore, one should now consider this avenue of investigation as a putative source of biomarkers and therapeutic targets to personalize the treatment of metabolic disease and its co-morbidities. Gut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes, and hepatic steatosis, the mechanisms causal to the disease could be related to the translocation of microbiota from the gut to the tissues, which induces inflammation. The mechanisms regulating such a process are based on the crosstalk between the gut microbiota and the host immune system. The hologenome theory of evolution supports this concept and implies that therapeutic strategies aiming to control glycemia should take into account both the gut microbiota and the host immune system. This review discusses the latest evidence regarding the bidirectional impact of the gut microbiota on host immune system crosstalk for the control of metabolic disease, hyperglycemia, and obesity. To avoid redundancies with the literature, we will focus our attention on the intestinal immune system, identifying evidence for the generation of novel therapeutic strategies, which could be based on the control of the translocation of gut bacteria to tissues. Such novel strategies should hamper the role played by gut microbiota dysbiosis on the development of metabolic inflammation. Recent evidence in rodents allows us to conclude that an impaired intestinal immune system characterizes and could be causal in the development of metabolic disease. The fine understanding of the molecular mechanisms should allow for the development of a first line of treatment for metabolic disease and its co-morbidities. 10.1051/jbio/2017008
    The intestinal microbiota fuelling metabolic inflammation. Tilg Herbert,Zmora Niv,Adolph Timon E,Elinav Eran Nature reviews. Immunology Low-grade inflammation is the hallmark of metabolic disorders such as obesity, type 2 diabetes and nonalcoholic fatty liver disease. Emerging evidence indicates that these disorders are characterized by alterations in the intestinal microbiota composition and its metabolites, which translocate from the gut across a disrupted intestinal barrier to affect various metabolic organs, such as the liver and adipose tissue, thereby contributing to metabolic inflammation. Here, we discuss some of the recently identified mechanisms that showcase the role of the intestinal microbiota and barrier dysfunction in metabolic inflammation. We propose a concept by which the gut microbiota fuels metabolic inflammation and dysregulation. 10.1038/s41577-019-0198-4
    The Intestinal Microbiota in Metabolic Disease. Woting Anni,Blaut Michael Nutrients Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions. 10.3390/nu8040202
    Metabolic and immunologic control of intestinal cell function by mTOR. Fritsch Stephanie D,Weichhart Thomas International immunology The intestinal epithelium is one of the most quickly dividing tissues in our body, combining the absorptive advantages of a single layer with the protection of a constantly renewing barrier. It is continuously exposed to nutrients and commensal bacteria as well as microbial and host-derived metabolites, but also to hazards such as pathogenic bacteria and toxins. These environmental cues are sensed by the mucosa and a vast repertory of immune cells, especially macrophages. A disruption of intestinal homeostasis in terms of barrier interruption can lead to inflammatory bowel diseases and colorectal cancer, and macrophages have an important role in restoring epithelial function following injury. The mammalian/mechanistic target of rapamycin (mTOR) signalling pathway senses environmental cues and integrates metabolic responses. It has emerged as an important regulator of intestinal functions in homeostasis and disease. In this review, we are going to discuss intestinal mTOR signalling and metabolic regulation in different intestinal cell populations with a special focus on immune cells and their actions on intestinal function. 10.1093/intimm/dxaa015
    Akkermansia muciniphila: a promising target for the therapy of metabolic syndrome and related diseases. Zhou Ji-Chao,Zhang Xiao-Wei Chinese journal of natural medicines The probiotic Akkermansia muciniphila (A. muciniphila) is an intestinal bacterium that was first identified in human feces in 2004. Its specialization in mucin degradation makes it a key microorganism that maintains intestinal mucosal barrier function. As an unique representative strain of the phylum Verrucomicrobia that can be cultured in vitro, A. muciniphila is much easier to detect by metagenomic analysis of intestinal flora. In the past few years, A. muciniphila has been getting increasing attention for the positive correlation between its intestinal colonization and host homeostatic metabolism. In this review, we summarize the relationship between A. muciniphila and host health and diseases, especially focusing on metabolic diseases and related mechanisms, as well as the natural food and drug-derived substrates affecting its colonization in the host, expecting to provide evidence and clues for the development of drugs targeting A. muciniphila. 10.1016/S1875-5364(19)30101-3
    Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance. Clavel Thomas,Desmarchelier Charles,Haller Dirk,Gérard Philippe,Rohn Sascha,Lepage Patricia,Daniel Hannelore Gut microbes The trillions of bacterial cells that colonize the mammalian digestive tract influence both host physiology and the fate of dietary compounds. Gnotobionts and fecal transplantation have been instrumental in revealing the causal role of intestinal bacteria in energy homeostasis and metabolic dysfunctions such as type-2 diabetes. However, the exact contribution of gut bacterial metabolism to host energy balance is still unclear and knowledge about underlying molecular mechanisms is scant. We have previously characterized cecal bacterial community functions and host responses in diet-induced obese mice using omics approaches. Based on these studies, we here discuss issues on the relevance of mouse models, give evidence that the metabolism of cholesterol-derived compounds by gut bacteria is of particular importance in the context of metabolic disorders and that dominant species of the family Coriobacteriaceae are good models to study these functions. 10.4161/gmic.29331
    Intestinal microflora and metabolic diseases. Serino M,Luche E,Chabo C,Amar J,Burcelin R Diabetes & metabolism Recent advances in molecular sequencing technology have allowed researchers to answer major questions regarding the relationship between a vast genomic diversity-such as found in the intestinal microflora-and host physiology. Over the past few years, it has been established that, in obesity, type 1 diabetes and Crohn's disease-to cite but a few-the intestinal microflora play a pathophysiological role and can induce, transfer or prevent the outcome of such conditions. A few of the molecular vectors responsible for this regulatory role have been determined. Some are related to control of the immune, vascular, endocrine and nervous systems located in the intestines. However, more important is the fact that the intestinal microflora-to-host relationship is bidirectional, with evidence of an impact of the host genome on the intestinal microbiome. This means that the ecology shared by the host and gut microflora should now be considered a new player that can be manipulated, using pharmacological and nutritional approaches, to control physiological functions and pathological outcomes. What now remains is to demonstrate the molecular connection between the intestinal microflora and metabolic diseases. We propose here that the proinflammatory lipopolysaccharides play a causal role in the onset of metabolic disorders. 10.1016/j.diabet.2009.03.003
    The role of intestinal microbiota in the pathogenesis of metabolic diseases. Węgielska Iwona,Suliburska Joanna Acta scientiarum polonorum. Technologia alimentaria The incidence of metabolic diseases is increasing rapidly all over the world. This situation has led researchers to attempt to explain the pathomechanisms of these disorders and to develop specific recommendations for the prevention and treatment of diseases such as obesity, type-2 diabetes, and atherosclerosis. Recent studies show clear evidence of the role of human intestinal microbiota in health and in predispositions to diseases. Gut microbiota affect a number of complex metabolic reactions, significantly altering the functioning of the human body. Numerous experiments have shown the key role played by the formation process of the intestinal ecosystem in the early stages of human life for programming its metabolic health. The following article is a compilation of the literature available on the formation of the complex intestinal ecosystem and its impact on the incidence of diseases such as obesity, type-2 diabetes, and atherosclerosis. 10.17306/J.AFS.2016.2.20
    Intestinal microbiota and the immune system in metabolic diseases. Sittipo Panida,Lobionda Stefani,Lee Yun Kyung,Maynard Craig L Journal of microbiology (Seoul, Korea) The intestinal microbiota is comprised of millions of microorganisms that reside in the gastrointestinal tract and consistently interact with the host. Host factors such as diet and disease status affect the composition of the microbiota, while the microbiota itself produces metabolites that can further manipulate host physiology. Dysbiosis of the intestinal microbiota has been characterized in patients with certain metabolic diseases, some of which involve damage to the host intestinal epithelial barrier and alterations in the immune system. In this review, we will discuss the consequences of dietdependent bacterial dysbiosis in the gastrointestinal tract, and how the associated interaction with epithelial and immune cells impacts metabolic diseases. 10.1007/s12275-018-7548-y
    Comparative analysis of the intestinal flora in type 2 diabetes and nondiabetic mice. Horie Masanori,Miura Takamasa,Hirakata Satomi,Hosoyama Akira,Sugino Sakiko,Umeno Aya,Murotomi Kazutoshi,Yoshida Yasukazu,Koike Taisuke Experimental animals A relationship between type 2 diabetes mellitus (T2DM) and intestinal flora has been suggested since development of analysis technology for intestinal flora. An animal model of T2DM is important for investigation of T2DM. Although there are some animal models of T2DM, a comparison of the intestinal flora of healthy animals with that of T2DM animals has not yet been reported. The intestinal flora of Tsumura Suzuki Obese Diabetes (TSOD) mice was compared with that of Tsumura, Suzuki, Non Obesity (TSNO) mice in the present study. The TSOD mice showed typical type 2 diabetes symptoms, which were high-fat diet-independent. The TSOD and the TSNO mouse models were derived from the same strain, ddY. In this study, we compared the intestinal flora of TSOD mice with that if TSNO mice at 5 and 12 weeks of age. We determined that that the number of operational taxonomic units (OTUs) was significantly higher in the cecum of TSOD mice than in that of TSNO mice. The intestinal flora of the cecum and that of the feces were similar between the TSNO and the TSOD strains. The dominant bacteria in the cecum and feces were of the phyla Firmicutes and Bacteroidetes. However, the content of some bacterial species varied between the two strains. The percentage of Lactobacillus spp. within the general intestinal flora was higher in TSOD mice than in TSNO mice. In contrast, the percentages of order Bacteroidales and family Lachnospiraceae were higher in TSNO mice than in TSOD mice. Some species were observed only in TSOD mice, such as genera Turicibacter and SMB53 (family Clostridiaceae), the percentage of which were 3.8% and 2.0%, respectively. Although further analysis of the metabolism of the individual bacteria in the intestinal flora is essential, genera Turicibacter and SMB53 may be important for the abnormal metabolism of type 2 diabetes. 10.1538/expanim.17-0021
    Gut: A key player in the pathogenesis of type 2 diabetes? Muscogiuri Giovanna,Balercia Giancarlo,Barrea Luigi,Cignarelli Angelo,Giorgino Francesco,Holst Jens J,Laudisio Daniela,Orio Francesco,Tirabassi Giacomo,Colao Annamaria Critical reviews in food science and nutrition The gut regulates glucose and energy homeostasis; thus, the presence of ingested nutrients into the gut activates sensing mechanisms that affect both glucose homeostasis and regulate food intake. Increasing evidence suggest that gut may also play a key role in the pathogenesis of type 2 diabetes which may be related to both the intestinal microbiological profile and patterns of gut hormones secretion. Intestinal microbiota includes trillions of microorganisms but its composition and function may be adversely affected in type 2 diabetes. The intestinal microbiota may be responsible of the secretion of molecules that may impair insulin secretion/action. At the same time, intestinal milieu regulates the secretion of hormones such as GLP-1, GIP, ghrelin, gastrin, somatostatin, CCK, serotonin, peptide YY, GLP-2, all of which importantly influence metabolism in general and in particular glucose metabolism. Thus, the aim of this paper is to review the current evidence on the role of the gut in the pathogenesis of type 2 diabetes, taking into account both hormonal and microbiological aspects. 10.1080/10408398.2016.1252712
    Gut Microbiota and Type 1 Diabetes. Han Hui,Li Yuying,Fang Jun,Liu Gang,Yin Jie,Li Tiejun,Yin Yulong International journal of molecular sciences Recently, the onset of type 1 diabetes (T1D) has increased rapidly and became a major public health concern worldwide. Various factors are associated with the development of T1D, such as diet, genome, and intestinal microbiota. The gastrointestinal (GI) tract harbors a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host homeostasis and metabolic diseases. Recent evidence shows that altered gut bacterial composition (dysbiosis) is highly associated with the pathogenesis of insulin dysfunction and T1D and, thus, targeting gut microbiota may serve as a therapeutic potential for T1D patients. In this study, we updated the effect of gut microbiota on T1D and potential mechanisms were discussed. 10.3390/ijms19040995
    Regulatory properties of the intestinal microbiome effecting the development and treatment of diabetes. Romano-Keeler Joann,Weitkamp Jöern-Hendrik,Moore Daniel J Current opinion in endocrinology, diabetes, and obesity PURPOSE OF REVIEW:The microbiome continues to demonstrate an important role in immune and metabolic programming. This review will focus on the mechanistic implications of recent findings for diabetes pathogenesis and treatment. RECENT FINDINGS:Multiple techniques are developing to specify the microbiome. At the same time, new insights have emerged into local interactions of microbial products with human development. New findings demonstrate that key bacteria and their products result in the programming of diabetes-modulating Th17 and regulatory T lymphocytes within and outside the intestine. The role of the bacterial metagenome in programming human metabolism has also revealed new insights. In turn, these findings suggest a framework in which the microbiome may be modified to change the course of diabetes. SUMMARY:The microbiome is a key regulator of metabolism and immunity. Specific bacteria and their secreted products are now known to program Th17 and regulatory T-cell development, which may change the course of diabetes. Bacterial genomics are demonstrating important, modifiable roles of bacterial gene products in metabolism. Further understanding of this symbiotic relationship will provide new avenues for intervention in diabetes. 10.1097/MED.0b013e3283514d43
    Vitamin D and prebiotics may benefit the intestinal microbacteria and improve glucose homeostasis in prediabetes and type 2 diabetes. Barengolts Elena Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists OBJECTIVE:To review the role of human large bowel microbacteria (microbiota) in the glucose homeostasis, to address vitamin D (VD) and prebiotics interactions with microbiota, and to summarize recent randomized clinical trials (RCTs) of VD and prebiotics supplementation in prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). METHODS:Primary literature was reviewed in the following areas: composition and activity of human microbiota associated with PreDM and T2DM, interactions between microbiota and glucose homeostasis, the interaction of microbiota with VD/prebiotics, and RCTs of VD/prebiotics in subjects with PreDM or T2DM. RESULTS:The human microbiota is comprised of 100 trillion bacteria with an aggregate genome that is 150-fold larger than the human genome. Data from the animal models and human studies reveal that an "obesogenic" diet results into the initial event of microbiota transformation from symbiosis to dysbiosis. The microbial antigens, such as Gram(-) bacteria and lipopolysaccharide (LPS), translocate to the host interior and trigger increased energy harvesting and Toll-like receptor (TLR) activation with subsequent inflammatory pathways signaling. The "double hit" of steatosis (ectopic fat accumulation) and "-itis" (inflammation) and contribution of "corisks" (e.g., vitamin D deficiency [VDD]) are required to activate molecular signaling, including impaired insulin signaling and secretion, that ends with T2DM and associated diseases. Dietary changes (e.g., prebiotics, VD supplementation) may ameliorate this process if initiated prior to the process becoming irreversible. CONCLUSION:Emerging evidence suggests an important role of microbiota in glucose homeostasis. VD supplementation and prebiotics may be useful in managing PreDM and T2DM. 10.4158/EP12263.RA
    [Intestinal microflora, obesity and type 2 diabetes]. Bondarenko V M,Maleev V V,Likhoded V G Zhurnal mikrobiologii, epidemiologii i immunobiologii The review of data of the literature on a role of intestinal microflora, genetic features of a macroorganism, exogenic factors and character of a food is presented at obesity and a type 2 diabetes. Researches establish, that development in experimental animals of the induced obesity and the type 2 diabetes, depends on a diet and presence of intestinal microflora. The factors increasing permeability mucous intestines, promote a translocation of intestinal automicroflora and its toxins into macroorganism and a system blood-circulation. Long introduction LPS (endotoxin) of gram-negative bacteria to the special laboratory animals led to development of inflammatory reaction, adiposity and resistance to insulin. The specified phenomena did not develop at LPS introduction to the animals, who have lost receptor CD14 which is necessary for linkage and endotoxin action. Data about change of intestinal microflora and a role of immune infringements are discussed at obesity and the type 2 diabetes occurring into background of low-grade chronic inflammation and metabolic disorders.
    Gut microbiota, probiotics and diabetes. Gomes Aline Corado,Bueno Allain Amador,de Souza Rávila Graziany Machado,Mota João Felipe Nutrition journal Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes. 10.1186/1475-2891-13-60
    Probiotic strains and mechanistic insights for the treatment of type 2 diabetes. Hampe Christiane S,Roth Christian L Endocrine INTRODUCTION:The intestinal microbial composition appears to differ between healthy controls and individuals with Type 2 diabetes (T2D). This observation has led to the hypothesis that perturbations of the intestinal microbiota may contribute to the development of T2D. Manipulations of the intestinal microbiota may therefore provide a novel approach in the prevention and treatment of T2D. Indeed, fecal transplants have shown promising results in both animal models for obesity and T2D and in human clinical trials. To avoid possible complications associated with fecal transplants, probiotics are considered as a viable alternative therapy. An important, however often underappreciated, characteristic of probiotics is that individual strains may have different, even opposing, effects on the host. This strain specificity exists also within the same species. A comprehensive understanding of the underlying mechanisms at the strain level is therefore crucial for the selection of suitable probiotic strains. PURPOSE:The aim of this review is to discuss the mechanisms employed by specific probiotic strains of the Lactobacillus and the Bifidobacterium genuses, which showed efficacy in the treatment of obesity and T2D. Some probiotic strains employ recurring beneficial effects, including the production of anti-microbial lactic acid, while other strains display highly unique features, such as hydrolysis of tannins. CONCLUSION:A major obstacle in the evaluation of probiotic strains lays in the great number of strains, differences in detection methodology and measured outcome parameters. The understanding of further research should be directed towards the development of standardized evaluation methods to facilitate the comparison of different studies. 10.1007/s12020-017-1433-z
    Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease. Brown Kirsty,DeCoffe Daniella,Molcan Erin,Gibson Deanna L Nutrients The gastrointestinal (GI) microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn's disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed. 10.3390/nu4081095
    Effectiveness of probiotics in type 2 diabetes: a meta-analysis. Kasińska Marta A,Drzewoski Józef Polskie Archiwum Medycyny Wewnetrznej INTRODUCTION:An increasing number of studies suggest that the use of probiotics may have a beneficial effect in patients with type 2 diabetes. OBJECTIVES:The aim of the study was to assess the ability of probiotics to modify selected cardiometabolic risk factors in subjects with type 2 diabetes. METHODS:PubMed, Embase, Cochrane Library, and Scopus databases were thoroughly reviewed up to January 2015 to search for randomized controlled trials (RCTs) that examined the effect of probiotics on selected modifiable cardiometabolic parameters in patients with type 2 diabetes. The following endpoints were considered: fasting plasma glucose (FPG), insulin concentration, insulin resistance, hemoglobin A1c (HbA1c), as well as the levels of total cholesterol, triglycerides, low-density and high-density lipoprotein cholesterols, and C-reactive protein (CRP). A total of 571 RCTs were initially identified, of which 8 trials with 438 individuals were selected for meta-analysis. The effects of probiotics were calculated for each parameter. RESULTS:The meta-analysis showed a significant effect of probiotics on reducing HbA1c levels (standardized mean difference [SMD], -0.81; confidence interval [CI], -1.33 to -0.29, P = 0.0023; I2 = 68.44%; P = 0.0421 for heterogeneity) and HOMA-IR (SMD, -2.10; CI -3.00 to -1.20, P <0.001; I2 = 82.91%; P = 0.0029 for heterogeneity). Supplementation with probiotics did not have a significant effect on FPG, insulin, and CRP levels as well as the lipid profile. CONCLUSIONS:Our meta-analysis suggests that probiotic supplementation might improve, at least to some extent, metabolic control in subjects with type 2 diabetes. However, larger well-designed, longterm RCTs are needed to confirm any potentially beneficial relationship between the use of probiotics and modifiable cardiometabolic risk factors in patients with type 2 diabetes. 10.20452/pamw.3156
    Gut dysbiosis and detection of "live gut bacteria" in blood of Japanese patients with type 2 diabetes. Sato Junko,Kanazawa Akio,Ikeda Fuki,Yoshihara Tomoaki,Goto Hiromasa,Abe Hiroko,Komiya Koji,Kawaguchi Minako,Shimizu Tomoaki,Ogihara Takeshi,Tamura Yoshifumi,Sakurai Yuko,Yamamoto Risako,Mita Tomoya,Fujitani Yoshio,Fukuda Hiroshi,Nomoto Koji,Takahashi Takuya,Asahara Takashi,Hirose Takahisa,Nagata Satoru,Yamashiro Yuichiro,Watada Hirotaka Diabetes care OBJECTIVE:Mounting evidence indicates that the gut microbiota are an important modifier of obesity and diabetes. However, so far there is no information on gut microbiota and "live gut bacteria" in the systemic circulation of Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS:Using a sensitive reverse transcription-quantitative PCR (RT-qPCR) method, we determined the composition of fecal gut microbiota in 50 Japanese patients with type 2 diabetes and 50 control subjects, and its association with various clinical parameters, including inflammatory markers. We also analyzed the presence of gut bacteria in blood samples. RESULTS:The counts of the Clostridium coccoides group, Atopobium cluster, and Prevotella (obligate anaerobes) were significantly lower (P < 0.05), while the counts of total Lactobacillus (facultative anaerobes) were significantly higher (P < 0.05) in fecal samples of diabetic patients than in those of control subjects. Especially, the counts of Lactobacillus reuteri and Lactobacillus plantarum subgroups were significantly higher (P < 0.05). Gut bacteria were detected in blood at a significantly higher rate in diabetic patients than in control subjects (28% vs. 4%, P < 0.01), and most of these bacteria were Gram-positive. CONCLUSIONS:This is the first report of gut dysbiosis in Japanese patients with type 2 diabetes as assessed by RT-qPCR. The high rate of gut bacteria in the circulation suggests translocation of bacteria from the gut to the bloodstream. 10.2337/dc13-2817
    Diabetes-mediated promotion of colon mucosa carcinogenesis is associated with mitochondrial dysfunction. Del Puerto-Nevado Laura,Santiago-Hernandez Aranzazu,Solanes-Casado Sonia,Gonzalez Nieves,Ricote Marta,Corton Marta,Prieto Isabel,Mas Sebastian,Sanz Ana Belen,Aguilera Oscar,Gomez-Guerrero Carmen,Ayuso Carmen,Ortiz Alberto,Rojo Federico,Egido Jesus,Garcia-Foncillas Jesus,Minguez Pablo,Alvarez-Llamas Gloria, Molecular oncology Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of cancer, including colon cancer (CC). However, we recently reported no influence of T2DM on CC prognosis, suggesting that any effect might be at the early stages of tumor development. We hypothesized that T2DM may create an environment in the healthy tissue, which acts as a carcinogenesis driver in agreement with the field of cancerization concept. Here, we focused on early carcinogenesis by analyzing paired tumor and normal colonic mucosa samples from the same patients. The proteome of CC and paired mucosa was quantitatively analyzed in 28 individuals (12 diabetics and 16 nondiabetics) by mass spectrometry with isobaric labeling. Out of 3076 identified proteins, 425 were differentially expressed at the tumor in diabetics compared with nondiabetics. In the adjacent mucosa, 143 proteins were differentially expressed in diabetics and nondiabetics. An enrichment analysis of this signature pointed to mitochondria, ribosome, and translation. Only six proteins were upregulated by diabetes both in tumor and mucosa, of which five were mitochondrial proteins. Differential expression in diabetic versus nondiabetic mucosa was confirmed for MRPL53, MRPL18, and TIMM8B. Higher levels of MRPL18, TIMM8B, and EIF1A were also found in normal colon epithelial cells exposed to high-glucose conditions. We conclude that T2DM is associated with specific molecular changes in the normal mucosa of CC patients, consistent with field of cancerization in a diabetic environment. The mitochondrial protein signature identifies a potential therapeutic target that could underlie the higher risk of CC in diabetics. 10.1002/1878-0261.12531
    The role of Gut Microbiota in the development of obesity and Diabetes. Baothman Othman A,Zamzami Mazin A,Taher Ibrahim,Abubaker Jehad,Abu-Farha Mohamed Lipids in health and disease Obesity and its associated complications like type 2 diabetes (T2D) are reaching epidemic stages. Increased food intake and lack of exercise are two main contributing factors. Recent work has been highlighting an increasingly more important role of gut microbiota in metabolic disorders. It's well known that gut microbiota plays a major role in the development of food absorption and low grade inflammation, two key processes in obesity and diabetes. This review summarizes key discoveries during the past decade that established the role of gut microbiota in the development of obesity and diabetes. It will look at the role of key metabolites mainly the short chain fatty acids (SCFA) that are produced by gut microbiota and how they impact key metabolic pathways such as insulin signalling, incretin production as well as inflammation. It will further look at the possible ways to harness the beneficial aspects of the gut microbiota to combat these metabolic disorders and reduce their impact. 10.1186/s12944-016-0278-4
    Microbiota and diabetes: an evolving relationship. Tilg Herbert,Moschen Alexander R Gut The gut microbiota affects numerous biological functions throughout the body and its characterisation has become a major research area in biomedicine. Recent studies have suggested that gut bacteria play a fundamental role in diseases such as obesity, diabetes and cardiovascular disease. Data are accumulating in animal models and humans suggesting that obesity and type 2 diabetes (T2D) are associated with a profound dysbiosis. First human metagenome-wide association studies demonstrated highly significant correlations of specific intestinal bacteria, certain bacterial genes and respective metabolic pathways with T2D. Importantly, especially butyrate-producing bacteria such as Roseburia intestinalis and Faecalibacterium prausnitzii concentrations were lower in T2D subjects. This supports the increasing evidence, that butyrate and other short-chain fatty acids are able to exert profound immunometabolic effects. Endotoxaemia, most likely gut-derived has also been observed in patients with metabolic syndrome and T2D and might play a key role in metabolic inflammation. A further hint towards an association between microbiota and T2D has been derived from studies in pregnancy showing that major gut microbial shifts occurring during pregnancy affect host metabolism. Interestingly, certain antidiabetic drugs such as metformin also interfere with the intestinal microbiota. Specific members of the microbiota such as Akkermansia muciniphila might be decreased in diabetes and when administered to murines exerted antidiabetic effects. Therefore, as a 'gut signature' becomes more evident in T2D, a better understanding of the role of the microbiota in diabetes might provide new aspects regarding its pathophysiological relevance and pave the way for new therapeutic principles. 10.1136/gutjnl-2014-306928
    Regional gastrointestinal pH profile is altered in patients with type 1 diabetes and peripheral neuropathy. Wegeberg A-M L,Brock C,Brock B,Farmer A D,Hobson A R,Semler J R,Scott S M Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society BACKGROUND:Gastrointestinal (GI) symptoms, such as nausea and bloating, are common in people with type 1 diabetes (T1DM). Autonomic dysfunction can lead to changes in the GI secreto-motor function which can be associated with GI symptom development. We hypothesized that regional pH profiles in T1DM differs from health and would be associated with objective physiological/clinical markers. METHODS:Forty-seven T1DM with confirmed diabetic sensory peripheral neuropathy and 41 healthy age-matched subjects underwent standardized wireless motility capsule testing. T1DM completed the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale. Disease duration, glycemic control, insulin usage, and 24-hour heart rate variability testing were evaluated. KEY RESULTS:In comparison to healthy subjects, gastric, and large bowel median pH were lower in T1DM (1.8 ± 1.6 vs 2.9 ± 1.5, P = 0.001 and 6.7 ± 0.6 vs 7.0 ± 0.5, P = 0.003, respectively). Additionally, change in pH across the pylorus was lower while change in pH across the ileocecal junction was higher in T1DM (5.2 ± 1.5 vs 5.8 ± 0.5, P = 0.003 and 1.8 ± 0.4 vs 1.3 ± 0.4, P < 0.0001, respectively). No difference was found in small bowel median pH. Gastric median pH was associated with small bowel transit time (r = 0.30, P = 0.049). Change in pH across the pylorus was negatively associated with fasting glycose (r = -0.35, P = 0.027). Small bowel median pH was associated with nausea (r = 0.42, P = 0.005) and small bowel transit time (r = 0.48, P = 0.0007). Large bowel median pH was associated with nausea (r = 0.35, P = 0.018) and the total GCSI score (r = 0.34, P = 0.023). CONCLUSIONS AND INFERENCES:The GI pH profile in T1DM with DSPN is different from healthy subjects. Changes in pH profile may have important therapeutic implications and influence pharmacotherapeutic bioavailability. 10.1111/nmo.13407
    Gut microbiome dysbiosis and increased intestinal permeability in children with islet autoimmunity and type 1 diabetes: A prospective cohort study. Harbison Jessica E,Roth-Schulze Alexandra J,Giles Lynne C,Tran Cuong D,Ngui Katrina M,Penno Megan A,Thomson Rebecca L,Wentworth John M,Colman Peter G,Craig Maria E,Morahan Grant,Papenfuss Anthony T,Barry Simon C,Harrison Leonard C,Couper Jennifer J Pediatric diabetes AIMS/HYPOTHESIS:To investigate the longitudinal relationship between the gut microbiome, circulating short chain fatty acids (SCFAs) and intestinal permeability in children with islet autoimmunity or type 1 diabetes and controls. METHODS:We analyzed the gut bacterial microbiome, plasma SCFAs, small intestinal permeability and dietary intake in 47 children with islet autoimmunity or recent-onset type 1 diabetes and in 41 unrelated or sibling controls over a median (range) of 13 (2-34) months follow-up. RESULTS:Children with multiple islet autoantibodies (≥2 IA) or type 1 diabetes had gut microbiome dysbiosis. Anti-inflammatory Prevotella and Butyricimonas genera were less abundant and these changes were not explained by differences in diet. Small intestinal permeability measured by blood lactulose:rhamnose ratio was higher in type 1 diabetes. Children with ≥2 IA who progressed to type 1 diabetes (progressors), compared to those who did not progress, had higher intestinal permeability (mean [SE] difference +5.14 [2.0], 95% confidence interval [CI] 1.21, 9.07, P = .006), lower within-sample (alpha) microbial diversity (31.3 [11.2], 95% CI 9.3, 53.3, P = .005), and lower abundance of SCFA-producing bacteria. Alpha diversity (observed richness) correlated with plasma acetate levels in all groups combined (regression coefficient [SE] 0.57 [0.21], 95% CI 0.15, 0.99 P = .008). CONCLUSIONS/INTERPRETATION:Children with ≥2 IA who progress to diabetes, like those with recent-onset diabetes, have gut microbiome dysbiosis associated with increased intestinal permeability. Interventions that expand gut microbial diversity, in particular SCFA-producing bacteria, may have a role to decrease progression to diabetes in children at-risk. 10.1111/pedi.12865
    Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective. Han Jun-Ling,Lin Hui-Ling World journal of gastroenterology The incidence of type 2 diabetes (T2DM) is rapidly increasing worldwide. However, the pathogenesis of T2DM has not yet been well explained. Recent evidence suggests that the intestinal microbiota composition is associated with obesity and T2DM. In this review, we provide an overview about the mechanisms underlying the role of intestinal microbiota in the pathogenesis of T2DM. There is clear evidence that the intestinal microbiota influences the host through its effect on body weight, bile acid metabolism, proinflammatory activity and insulin resistance, and modulation of gut hormones. Modulating gut microbiota with the use of probiotics, prebiotics, antibiotics, and fecal microbiota transplantation may have benefits for improvement in glucose metabolism and insulin resistance in the host. Further studies are required to increase our understanding of the complex interplay between intestinal microbiota and the host with T2DM. Further studies may be able to boost the development of new effective therapeutic approaches for T2DM. 10.3748/wjg.v20.i47.17737
    The Role of Bile Acids in Glucose Metabolism and Their Relation with Diabetes. González-Regueiro José Alberto,Moreno-Castañeda Lidia,Uribe Misael,Chávez-Tapia Norberto C Annals of hepatology Bile acids (BAs), the end products of cholesterol catabolism, are essential for the absorption of lipids and fat-soluble vitamins; but they have also emerged as novel signaling molecules that act as metabolic regulators. It has been well described that the enterohepatic circulation, a nuclear (FXR) and a cytoplasmic (TGR5/M-BAR) receptor aid in controlling hepatic bile acid synthesis. Modulating bile acid synthesis greatly impacts in metabolism, because these receptors also are implicated in glucose, lipid, and energy expenditure. Recent studies had revealed the way these receptors participate in regulating gluconeogenesis, peripheral insulin sensitivity, glycogen synthesis, glucagon like peptide 1 (GLP-1) and insulin secretion. Nowadays, it is demonstrated that enhancing bile acid signaling in the intestine contributes to the metabolic benefits of bile acid sequestrants and bariatric surgery on glucose homeostasis. This paper discusses the role of bile acid as regulators of glucose metabolism and their potential as therapeutic targets for diabetes. 10.5604/01.3001.0010.5672
    Association of Intestinal Microbiota with Metabolic Markers and Dietary Habits in Patients with Type 2 Diabetes. Yamaguchi Yoshiharu,Adachi Kazunori,Sugiyama Tomoya,Shimozato Akihiro,Ebi Masahide,Ogasawara Naotaka,Funaki Yasushi,Goto Chiho,Sasaki Makoto,Kasugai Kunio Digestion BACKGROUND/AIMS:Evidence suggests that intestinal microbiota, along with factors such as diet and host genetics, contributes to obesity, metabolic dysfunction and diabetes. Therefore, we examined the relationship between gut microbiota, blood metabolic markers, dietary habits and fecal short-chain fatty acids (SCFAs) in patients with type 2 diabetes mellitus (T2DM). METHODS:Dietary habits, blood and fecal samples from 59 T2DM patients were recruited, and the association of intestinal microbiota with metabolic markers and dietary habits was analyzed. RESULTS:Total energy intake was 1,692 ± 380 kcal/day. Carbohydrate, fat and protein intakes were 57.5 ± 5.2, 23.2 ± 5.3 and 13.2 ± 2.2%, respectively. Dietary habits - high carbohydrate, fat, and protein intake - were associated with increased counts of Clostridium clusters IV and XI and decreased counts of Bifidobacterium spp., order Lactobacillales and Clostridium cluster IV. Protein intake was negatively correlated with fecal acetate and total SCFAs. Total SCFAs, propionate and acetate were negatively correlated with blood insulin levels and the homeostasis model of insulin resistance. CONCLUSION:Diets low in protein and carbohydrates favor a healthy gut microbiome and improve glucose tolerance in T2DM patients, although further elucidation of the role of the gut microbiome could lead to better therapies and prophylaxes. 10.1159/000447690
    Long term effect of gut microbiota transfer on diabetes development. Peng Jian,Narasimhan Sukanya,Marchesi Julian R,Benson Andrew,Wong F Susan,Wen Li Journal of autoimmunity The composition of the gut microbiome represents a very important environmental factor that influences the development of type 1 diabetes (T1D). We have previously shown that MyD88-deficient non-obese diabetic (MyD88-/-NOD) mice, that were protected from T1D development, had a different composition of gut microbiota compared to wild type NOD mice. The aim of our study was to investigate whether this protection could be transferred. We demonstrate that transfer of gut microbiota from diabetes-protected MyD88-deficient NOD mice, reduced insulitis and significantly delayed the onset of diabetes. Gut bacteria from MyD88-deficient mice, administered over a 3-week period, starting at 4 weeks of age, stably altered the family composition of the gut microbiome, with principally Lachnospiraceae and Clostridiaceae increased and Lactobacillaceae decreased. The transferred mice had a higher concentration of IgA and TGFβ in the lumen that was accompanied by an increase in CD8(+)CD103(+) and CD8αβ T cells in the lamina propria of the large intestine. These data indicate not only that gut bacterial composition can be altered after the neonatal/weaning period, but that the composition of the microbiome affects the mucosal immune system and can delay the development of autoimmune diabetes. This result has important implications for the development of probiotic treatment for T1D. 10.1016/j.jaut.2014.03.005
    Enteroendocrine K and L cells in healthy and type 2 diabetic individuals. Jorsal Tina,Rhee Nicolai A,Pedersen Jens,Wahlgren Camilla D,Mortensen Brynjulf,Jepsen Sara L,Jelsing Jacob,Dalbøge Louise S,Vilmann Peter,Hassan Hazem,Hendel Jakob W,Poulsen Steen S,Holst Jens J,Vilsbøll Tina,Knop Filip K Diabetologia AIMS/HYPOTHESIS:Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis. Knowledge of their distribution in humans is sparse and it is unknown whether alterations occur in type 2 diabetes. We aimed to evaluate the distribution of enteroendocrine K and L cells and relevant prohormone-processing enzymes (using immunohistochemical staining), and to evaluate the mRNA expression of the corresponding genes along the entire intestinal tract in individuals with type 2 diabetes and healthy participants. METHODS:In this cross-sectional study, 12 individuals with type 2 diabetes and 12 age- and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from approximately every 30 cm of the small intestine and from seven specific anatomical locations in the large intestine. RESULTS:Significantly different densities for cells positive for chromogranin A (CgA), glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, peptide YY, prohormone convertase (PC) 1/3 and PC2 were observed along the intestinal tract. The expression of CHGA did not vary along the intestinal tract, but the mRNA expression of GCG, GIP, PYY, PCSK1 and PCSK2 differed along the intestinal tract. Lower counts of CgA-positive and PC1/3-positive cells, respectively, were observed in the small intestine of individuals with type 2 diabetes compared with healthy participants. In individuals with type 2 diabetes compared with healthy participants, the expression of GCG and PYY was greater in the colon, while the expression of GIP and PCSK1 was greater in the small intestine and colon, and the expression of PCSK2 was greater in the small intestine. CONCLUSIONS/INTERPRETATION:Our findings provide a detailed description of the distribution of enteroendocrine K and L cells and the expression of their products in the human intestinal tract and demonstrate significant differences between individuals with type 2 diabetes and healthy participants. TRIAL REGISTRATION:NCT03044860. 10.1007/s00125-017-4450-9
    [Efficacy of pharmacological inhibition of intestinal saccharases in patients with diabetes mellitus type 2 and/or visceral obesity]. Ametov A S,Kamynina L L Terapevticheskii arkhiv Inhibitors of intestinal enzymes regulate carbohydrate metabolism reducing glycemic index, glycemic load of food and postprandial glycemia which is a prognostic factor of DM2-related cardiovascular complications and death. This class of drugs was proposed for DM2 treatment in 1970s but still holds perspectives. The article gives a detailed description of the mechanism of action, efficacy and safety of inhibitors of alpha-glucosidase and alpha-amilase in experimental and clinical controlled trials.
    Gut Microbiota Alterations can predict Hospitalizations in Cirrhosis Independent of Diabetes Mellitus. Bajaj Jasmohan S,Betrapally Naga S,Hylemon Phillip B,Thacker Leroy R,Daita Kalyani,Kang Dae Joong,White Melanie B,Unser Ariel B,Fagan Andrew,Gavis Edith A,Sikaroodi Masoumeh,Dalmet Swati,Heuman Douglas M,Gillevet Patrick M Scientific reports Diabetes (DM) is prevalent in cirrhosis and may modulate the risk of hospitalization through gut dysbiosis. We aimed to define the role of gut microbiota on 90-day hospitalizations and of concomitant DM on microbiota. Cirrhotic outpatients with/without DM underwent stool and sigmoid mucosal microbial analysis and were followed for 90 days. Microbial composition was compared between those with/without DM, and those who were hospitalized/not. Regression/ROC analyses for hospitalizations were performed using clinical and microbial features. 278 cirrhotics [39% hepatic encephalopathy (HE), 31%DM] underwent stool while 72 underwent mucosal analyses. Ultimately, 94 were hospitalized and they had higher MELD, proton pump inhibitor (PPI) use and HE without difference in DM. Stool/mucosal microbiota were significantly altered in those who were hospitalized (UNIFRAC p < = 1.0e-02). Specifically, lower stool Bacteroidaceae, Clostridiales XIV, Lachnospiraceae, Ruminococcacae and higher Enterococcaceae and Enterobacteriaceae were seen in hospitalized patients. Concomitant DM impacted microbiota UNIFRAC (stool, p = 0.003, mucosa, p = 0.04) with higher stool Bacteroidaceae and lower Ruminococcaeae. Stool Bacteroidaceaeae and Clostridiales XIV predicted 90-day hospitalizations independent of clinical predictors (MELD, HE, PPI). Stool and colonic mucosal microbiome are altered in cirrhotics who get hospitalized with independent prediction using stool Bacteroidaceae and Clostridiales XIV. Concomitant DM distinctly impacts gut microbiota without affecting hospitalizations. 10.1038/srep18559
    The intricate association between gut microbiota and development of type 1, type 2 and type 3 diabetes. Bekkering Pjotr,Jafri Ismael,van Overveld Frans J,Rijkers Ger T Expert review of clinical immunology It has been proposed that changes in the composition of gut microbiota contribute to the development of diabetes Types 1, 2 and 3 (the latter known as Alzheimer's disease). The onset of these diseases is affected by complex interactions of genetic and several environmental factors. Alterations in gut microbiota in combination with specific diets can result in increased intestinal permeability leading via a continuous state of low-grade inflammation to the development of insulin resistance. Since a change in composition of gut microbiota is also suggested to be the underlying factor for the development of obesity, it is obvious to link gut microbiota with the pathogenesis of diabetes. In addition, insulin resistance in the brain has been recently associated with Alzheimer's disease. These new paradigms in combination with data from studies with prebiotics and probiotics may lead to a novel way to control and even prevent diabetes in general. 10.1586/1744666X.2013.848793
    Lactobacillus casei CCFM419 attenuates type 2 diabetes via a gut microbiota dependent mechanism. Wang Gang,Li Xiangfei,Zhao Jianxin,Zhang Hao,Chen Wei Food & function Probiotics, as dietary supplements, transmit their major effects through the regulation of gut microbiota. According to a previous study, one possible mechanism of Lactobacillus casei CCFM419 protection against diabetes may involve gut flora. To test this hypothesis, high fat and streptozotocin-induced C57BL/6J mice were fed L. casei CCFM419 at 10, 10, and 10 colony forming units (CFU). Compared to untreated mice, 10 CFU of L. casei CCFM419 attenuated several symptoms of diabetes, including fasting blood glucose, postprandial blood glucose, glucose intolerance, and insulin resistance. In addition, this CFU level also decreased the levels of the inflammatory markers tumor necrosis factor-α and interleukin-6 and increased intestinal glucagon-like peptide-1 (GLP-1) levels, which are associated with the production of short chain fatty acids (SCFAs). The 16S rRNA gene sequencing of fecal samples demonstrated that 10 CFU of L. casei CCFM419 dramatically increased the abundance of Bacteroidetes and decreased the proportion of Firmicutes at the phylum level, and enriched Bifidobacterium, Lactobacillus, and SCFA-producing bacteria, including Allobaculum and Bacteroides. These findings suggested that L. casei CCFM419 modified the gut flora-SCFA-inflammation/GLP-1 mechanism to ameliorate type 2 diabetes. 10.1039/c7fo00593h
    Dietary compounds and traditional Chinese medicine ameliorate type 2 diabetes by modulating gut microbiota. Nie Qixing,Chen Haihong,Hu Jielun,Fan Songtao,Nie Shaoping Critical reviews in food science and nutrition Diabetes mellitus (DM) and its complications are major public health concerns which strongly influence the quality of humans' life. Modification of gut microbiota has been widely used for the management of diabetes. In this review, the relationship between diabetes and gut microbiota, as well as the effects of different dietary components and traditional Chinese medicine (TCM) on gut microflora are summarized. Dietary compounds and TCM possessing bioactive components (fiber and phytochemicals) first change the composition of gut microbiota (inhibiting pathogens and promoting the beneficial bacteria growth) and then influence the production of their metabolites, which would further modify the intestinal environment through inhibiting the production of detrimental compounds (such as lipopolysaccharide, hydrogen sulfide, indol, etc.). Importantly, metabolites (short chain fatty acids and other bioactive components) fermented/degraded by gut microbiota can target multiple pathways in intestine, liver, pancreas, etc., resulting in the improvement of gut health, glycemic control, lipids profile, insulin resistance and inflammation. Furthermore, understanding the interaction between different dietary components and gut microbiota, as well as underlying mechanisms would help design different diet formula for the management of diabetes. Further researches could focus on the combination of different dietary components for preventing and treating diabetes, based on the principle of "multiple components against multiple targets" from the perspective of gut microbiota. 10.1080/10408398.2018.1536646
    Resolution of diabetes mellitus by ileal transposition compared with biliopancreatic diversion in a nonobese animal model of type 2 diabetes. Zhang Guang Yong,Wang Tian Tian,Cheng Zhi Qiang,Feng Jin Bo,Hu San Yuau Canadian journal of surgery. Journal canadien de chirurgie BACKGROUND:It has been demonstrated that biliopancreatic diversion (BPD) and ileal transposition (IT) effectively induce weight loss and long-term control of type 2 diabetes in morbidly obese individuals. It is unknown whether the control of diabetes is better after IT or after BPD. The objective of this study was to investigate the effects of IT and BPD on the control of diabetes in an animal model. METHODS:We performed IT and BPD on 10- to 12-week-old Goto-Kakizaki rats with a spontaneous nonobese model of type 2 diabetes, and we performed a series of detection. The rats were observed for 24 weeks after surgery. RESULTS:Animals who underwent IT and BPD demonstrated improved glucose tolerance, insulin sensitivity and the secretion of glucagon-like peptide-1 compared with the sham-operated animals. Furthermore, IT resulted in a shorter duration of surgery and better postoperative recovery than BPD. CONCLUSION:This study provides strong evidence for the crucial role of the hindgut in the resolution of diabetes after duodenum-jejunum bypass or IT. We confirmed that IT was associated with better postoperative recovery than BPD and had a similar control of diabetes as BPD in nonobese animals with type 2 diabetes. 10.1503/cjs.044209
    [The microbial flora in the digestive tract and diabetes]. Svačina Štěpán Vnitrni lekarstvi The microbial flora in the digestive tract has been recently studied in relation to metabolic diseases. There are relations to both type 1 diabetes and type 2 diabetes. The intestinal flora is affected by diet, physical exercise and it significantly changes after bariatric surgeries. Giving birth by caesarean section affects the gut flora development and increases the risk of type 1 diabetes in further life of the child. Obese patients with type 2 diabetes may lack protective microbes which improve glucoregulation in the experiment or on the contrary their patogenous microbes may grow which have been proven to even be able to penetrate into abdominal adipose tissue and play a role, inter alia, in the hepatic impairment and systemic inflammation. Also vaccination against these microbes is under consideration. Microbiome can be also positively affected by metformin treatment. The transfer of intestinal flora by means of fecal transplantation can improve glucoregulation. The influencing of intestinal flora is likely to become a new mechanism of diabetes treatment.
    The health benefits of dietary fiber: beyond the usual suspects of type 2 diabetes mellitus, cardiovascular disease and colon cancer. Kaczmarczyk Melissa M,Miller Michael J,Freund Gregory G Metabolism: clinical and experimental Dietary fiber (DF) is deemed to be a key component in healthy eating. DF is not a static collection of undigestible plant materials that pass untouched or unencumbered through the gastrointestinal (GI) tract; instead, DFs are a vast array of complex saccharide-based molecules that can bind potential nutrients and nutrient precursors to prevent their absorption. Some DFs are fermentable, and the GI tract catabolism leads to the generation of various bioactive materials, such as short-chain fatty acids (SCFAs), that can markedly augment the GI tract biomass and change the composition of the GI tract flora. The health benefits of DFs include the prevention and mitigation of type 2 diabetes mellitus, cardiovascular disease and colon cancer. By modulating food ingestion, digestion, absorption and metabolism, DFs reduce the risk of hyperlipidemia, hypercholesterolemia and hyperglycemia. Emerging research has begun to investigate the role of DFs in immunomodulation. If substantiated, DFs could facilitate many biologic processes, including infection prevention and the improvement of mood and memory. This review describes the accepted physiologic functions of DFs and explores their new potential immune-based actions. 10.1016/j.metabol.2012.01.017
    Targeting gut microbiota as a possible therapy for diabetes. He Canxia,Shan Yujuan,Song Wei Nutrition research (New York, N.Y.) The incidence of diabetes has increased rapidly across the entire world in the last 2 decades. Accumulating evidence suggests that gut microbiota contribute to the pathogenesis of diabetes. Several studies have demonstrated that patients with diabetes are characterized by a moderate degree of gut microbial dysbiosis. However, there are still substantial controversies regarding altered composition of the gut microbiota and the underlying mechanisms by which gut microbiota interact with the body's metabolism. The purpose of this review is to define the association between gut microbiota and diabetes. In doing so an electronic search of studies published in English from January 2004 to the November 2014 in the National Library of Medicine, including the original studies that addressed the effects of gut microbiota on diabetes, energy metabolism, inflammation, the immune system, gut permeability and insulin resistance, was performed. Herein, we discuss the possible mechanisms by which the gut microbiota are involved in the development of diabetes, including energy metabolism, inflammation, the innate immune system, and the bowel function of the intestinal barrier. The compositional changes in the gut microbiota in type 2 and type 1 diabetes are also discussed. Moreover, we introduce the new findings of fecal transplantation, and use of probiotics and prebiotics as new treatment strategies for diabetes. Future research should be focused on defining the primary species of the gut microbiota and their exact roles in diabetes, potentially increasing the possibility of fecal transplants as a therapeutic strategy for diabetes. 10.1016/j.nutres.2015.03.002
    Screening Potential Probiotic Characteristics of Strains In Vitro and Intervention Effect on Type I Diabetes In Vivo. Abdelazez Amro,Abdelmotaal Heba,Evivie Smith Etareri,Melak Sherif,Jia Fang-Fang,Khoso Mir Hassan,Zhu Zong-Tao,Zhang Lu-Ji,Sami Rokayya,Meng Xiang-Chen BioMed research international Diabetes has become the third most serious threat to human health, after cancer and cardiovascular disease. Notably, is the most common species of LAB that produces -aminobutyric acid (GABA). The aim of this study is to clarify the effect of time, strain types, antibiotic concentrations, different levels of pH, and intestinal juices in aerobic or anaerobic conditions and the effect of interactions between these factors on the potential properties of KLDS 1.0727 and KLDS 1.0373, furthermore, antagonistic activity against foodborne pathogens. Moreover, another aim is to study the capability of KLDS 1.0727 and KLDS 1.0373 strains as gene carriers to express GABA that reduce the risk of type 1 diabetes in C57BL/6 mice as diabetic models. The obtained results exhibited the surprising tolerance of strains in vitro digestion models mimicking the conditions of the gastrointestinal tract, further, large antagonistic activity against foodborne pathogeneses. In vivo results displayed the significant effect on glucose level reduction, blood plasma, and histological assays of mice organs. As recommended, the use of strains should be widely shared in the market as a natural source of GABA in pharmaceutical and food applications. 10.1155/2018/7356173
    Prospects for primary prevention of type 1 diabetes by restoring a disappearing microbe. Insel Richard,Knip Mikael Pediatric diabetes Prevention of childhood-onset type 1 diabetes has become more urgent with its marked increased incidence in recent decades in the modern world. Temporally associated with the rising incidence of type 1 diabetes, as well as other autoimmune and allergic diseases in childhood in modern times, is the disappearance of Bifidobacterium and specifically Bifidobacterium longum subsp. infantis (B. infantis) predominance in the intestinal microbiota of breastfed, vaginally-delivered infants. B. infantis efficiently metabolizes human milk oligosaccharides (HMOs) without cross-feeding free sugar monomers to other commensals or pathogens and thereby dominates the intestinal microbiota of breastfed infants. Increased levels of short-chain fatty acids (SCFA), which stimulate both immunoregulation and healthy intestinal and pancreatic β-cell function, are generated by B. infantis. Based on recent observations of the intestinal microbiota in early life in young children who develop type 1 diabetes and demonstration of the robust preventive effects of SCFA in animal models of autoimmune diabetes, we hypothesize that restoring a B. infantis-dominant microbiota early in infancy will prevent islet autoimmunity and childhood-onset type 1 diabetes. 10.1111/pedi.12756
    Motilin concentrations in relation to gastro intestinal dysmotility in diabetes mellitus. Pendleton Hillevi,Ekman Rolf,Olsson Rolf,Ekberg Olle,Ohlsson Bodil European journal of internal medicine AIM:Dysmotility in the upper gastro intestinal (GI) tract are common problems in diabetics. Many peptides are involved in the regulation of the motility. The aim of this study was to examine whether plasma levels of motilin were related to dysfunction in the oesophagus and stomach in a well-defined diabetic patient group. METHODS:Nineteen patients with symptoms from the GI tract who had been examined with oesophageal manometry, gastric emptying scintigraphy and deep-breathing test were included. They received a fat-rich meal, after which blood samples were collected and analysed for motilin concentrations. RESULTS:Symptoms of abdominal fullness and gastro oesophageal reflux significantly associated with delayed gastric emptying, whereas no symptom correlated to oesophageal dysmotility. Plasma levels of motilin were increased after the fat-rich meal (p=0.000), with no difference between the groups. Abnormal manometry was characterized by aperistalsis and/or simultaneous contractions. The percentage of simultaneous contractions correlated to basic and peak motilin values (r(s)=0.898, p=0.006 and r(s)=0.842, p=0.017, respectively). Gastric emptying did not influence motilin concentrations. CONCLUSION:Plasma motilin concentrations vary with abnormalities of oesophageal motility in diabetics, but not with abnormalities of gastric emptying. 10.1016/j.ejim.2009.05.015
    The "perfect storm" for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Vaarala Outi,Atkinson Mark A,Neu Josef Diabetes It is often stated that type 1 diabetes results from a complex interplay between varying degrees of genetic susceptibility and environmental factors. While agreeing with this principal, our desire is that this Perspectives article will highlight another complex interplay potentially associated with this disease involving facets related to the gut, one where individual factors that, upon their interaction with each another, form a "perfect storm" critical to the development of type 1 diabetes. This trio of factors includes an aberrant intestinal microbiota, a "leaky" intestinal mucosal barrier, and altered intestinal immune responsiveness. Studies examining the microecology of the gastrointestinal tract have identified specific microorganisms whose presence appears related (either quantitatively or qualitatively) to disease; in type 1 diabetes, a role for microflora in the pathogenesis of disease has recently been suggested. Increased intestinal permeability has also been observed in animal models of type 1 diabetes as well as in humans with or at increased-risk for the disease. Finally, an altered mucosal immune system has been associated with the disease and is likely a major contributor to the failure to form tolerance, resulting in the autoimmunity that underlies type 1 diabetes. Herein, we discuss the complex interplay between these factors and raise testable hypotheses that form a fertile area for future investigations as to the role of the gut in the pathogenesis and prevention of type 1 diabetes. 10.2337/db08-0331
    Is there a role for gut microbiota in type 1 diabetes pathogenesis? Bibbò Stefano,Dore Maria Pina,Pes Giovanni Mario,Delitala Giuseppe,Delitala Alessandro P Annals of medicine Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by insufficient insulin production due to the destruction of insulin secreting β-cells in the Langerhans islets. A variety of factors, including chemicals, viruses, commensal bacteria and diet have been proposed to contribute to the risk of developing the disorder. In the last years, gut microbiota has been proposed as a main factor in T1D pathogenesis. Several alterations of gut microbiota composition were described both in animal model and in humans. The decrease of Firmicutes/Bacteroides ratio was the most frequent pattern described, in particular, in human studies. Furthermore, Bacteroides, Clostridium cluster XIVa, Lactobacillus, Bifidobacterium, and Prevotella relative abundances were different in healthy and affected subjects. Dysbiosis would seem to increase intestinal permeability and thus promote the development of a pro-inflammatory niche that stimulates β-cell autoimmunity in predisposed subjects. Preliminary studies on animal models were realized to investigate the role of gut microbiota modulation as therapy or prevention approach in predisposed animals: promising and stimulating results have been reported. Key message Dietary antigens and microbiota-derived products might act as triggers of T1D by causing a pro-inflammatory and metabolic dysfunctional environment. 10.1080/07853890.2016.1222449
    Intestinal peptide changes after bariatric and minimally invasive surgery: Relation to diabetes remission. Castagneto Gissey Lidia,Casella Mariolo James,Mingrone Geltrude Peptides Bariatric surgery is very effective in achieving and maintaining weight loss but it is also associated with improvement of obesity metabolic complications, primarily type 2 diabetes (T2D). Remission of T2D or at least a net improvement of glycemic control persists for at least 5 years. The bypass of duodenum and of the first portion of the jejunum up to the Treitz ligament as in Roux-en-Y Gastric Bypass (RYGB), or the bypass of the duodenum, the entire jejunum and the first tract of the ileum, such as in Bilio-Pancreatic Diversion (BPD), achieve different results on insulin sensitivity. Insulin resistance is the major driver of T2D manifesting long before insulin secretion failure. In fact, T2D development can be prevented by treatment with insulin sensitizing agents. Interestingly, RYGB improves hepatic insulin sensitivity while BPD ameliorates whole-body insulin sensitivity. Two major theories have been advocated to explain the early remission of T2D following RYGB or BPD before a meaningful weight loss takes place, the foregut and the hindgut hypotheses. The former holds that the bypass of the proximal intestine, i.e. duodenum and jejunum, prevents the secretion of signals - including nervous transmitters and hormones - promoting insulin resistance, the latter instead states that the delivery of nutrients directly into the ileum stimulates the secretion of hormones improving glucose disposal. The most studied candidate is Glucagon Like Peptide 1 (GLP1). However, while there is unambiguous evidence that GLP-1 stimulates insulin secretion, its direct action in lowering insulin resistance, independently of the effect on weight loss secondary to its satiety action, is utterly controversial. In this review we examine the effects on T2D and gastrointestinal peptide secretion produced by different types of metabolic surgery and by minimally invasive endoscopic surgery, whose utilization for the treatment of obesity and T2D is gaining wider interest and acceptance. 10.1016/j.peptides.2017.12.010
    The Future of Diabetes Management by Healthy Probiotic Microorganisms. Rad Aziz H,Abbasalizadeh Shamsi,Vazifekhah Shabnam,Abbasalizadeh Fatemeh,Hassanalilou Tohid,Bastani Parvin,Ejtahed Hanieh-Sadat,Soroush Ahmad-Reza,Javadi Mina,Mortazavian Amir M,Khalili Leila Current diabetes reviews BACKGROUND:Diabetes mellitus, a condition of multifactorial origin, is related to the intestinal microbiota by numerous molecular mechanisms. Controlling the vast increase in the prevalence of diabetes needs a natural and safe solution. Probiotics, known as live microorganisms that exert health benefits to the host, have anti-diabetic property. OBJECTIVE:This review will highlight the current evidences in probiotic effectiveness and future prospects for exploring probiotic therapy in the prevention and control of diabetes. METHODS:We searched Pub Med and Science Direct by using "Probiotics" and "Diabetes" for searching the studies aiming the application of probiotics and the beneficial effects of probiotics in diabetes prevention and control. RESULTS:It has been shown that probiotics can increase insulin sensitivity and reduce autoimmune responses by modulating intestinal microbiota and decreasing the inflammatory reactions and oxidative stress. Recent evidences show that probiotics influences the host through modulating intestinal permeability and mucosal immune response, manipulating eating behaviors by appetite-regulating hormones and controlling gut endocannabinoid (eCB) system that is believed to be associated with inflammation and diabetes. Moreover, modulating the intestinal microbiota by probiotics controls host metabolism by affecting energy extraction from food and by biochemically converting molecules derived from the host or from gut microbes themselves. CONCLUSION:Experimental and clinical evidences support the hypothesis that the modulation of the gut microbiota by probiotics could be effective in prevention and management of diabetes. 10.2174/1573399812666161014112515
    Comparison of gut microbiota in adult patients with type 2 diabetes and healthy individuals. Sedighi Mansour,Razavi Shabnam,Navab-Moghadam Fatemeh,Khamseh Mohammad E,Alaei-Shahmiri Fariba,Mehrtash Amirhosein,Amirmozafari Nour Microbial pathogenesis Recent studies indicate that inflammatory reactions leading to the development of type 2 diabetes mellitus (T2DM) may also contribute to variations in the composition of the intestinal microbiota, suggesting a relation between T2DM and bacterial residents in the intestinal tract. This case-control study was designed to evaluate the composition of the gut microbiota dominant bacterial groups in patients with T2DM compared to the healthy people. A total of 36 adult subjects (18 patients diagnosed with T2DM and 18 healthy persons) were included in the study. The intestinal microbiota composition was investigated by quantitative real-time polymerase chain reaction (qPCR) method using bacterial 16S rRNA gene. The quantities of two groups of bacteria were meaningfully different among T2DM patients and healthy individuals. While, the level of Lactobacillus was significantly higher in the patients with T2DM (P value < 0.001), Bifidobacterium was significantly more frequent in the healthy people (P value < 0.001). The quantities of Prevotella (P value = 0.0.08) and Fusobacterium (P value = 0.99) genera in faecal samples were not significantly different between the two groups. The significant alterations in dominant faecal bacterial genera found in T2DM patients participating in the current study highlight the link between T2DM disease and compositional variation in intestinal flora. These findings may be valuable for developing approaches to control T2DM by modifying the gut microbiota. More investigations with focus on various taxonomic levels (family, genus and species) of bacteria are necessary to clarify the exact relevance of changes in the gut microbial communities with the progression of T2DM disorder. 10.1016/j.micpath.2017.08.038
    Intestinal Immunomodulatory Cells (T Lymphocytes): A Bridge between Gut Microbiota and Diabetes. Li Qingwei,Gao Zezheng,Wang Han,Wu Haoran,Liu Yanwen,Yang Yingying,Han Lin,Wang Xinmiao,Zhao Linhua,Tong Xiaolin Mediators of inflammation Diabetes mellitus (DM) is one of the most familiar chronic diseases threatening human health. Recent studies have shown that the development of diabetes is closely related to an imbalance of the gut microbiota. Accordingly, there is increasing interest in how changes in the gut microbiota affect diabetes and its underlying mechanisms. Immunomodulatory cells play important roles in maintaining the normal functioning of the human immune system and in maintaining homeostasis. Intestinal immunomodulatory cells (IICs) are located in the intestinal mucosa and are regarded as an intermediary by which the gut microbiota affects physiological and pathological properties. Diabetes can be regulated by IICs, which act as a bridge linking the gut microbiota and DM. Understanding this bridge role of IICs may clarify the mechanisms by which the gut microbiota contributes to DM. Based on recent research, we summarize this process, thereby providing a basis for further studies of diabetes and other similar immune-related diseases. 10.1155/2018/9830939
    The Origin of New-Onset Diabetes After Liver Transplantation: Liver, Islets, or Gut? Ling Qi,Xu Xiao,Wang Baohong,Li Lanjuan,Zheng Shusen Transplantation New-onset diabetes is a frequent complication after solid organ transplantation. Although a number of common factors are associated with the disease, including recipient age, body mass index, hepatitis C infection, and use of immunosuppressive drugs, new-onset diabetes after liver transplantation (NODALT) has the following unique aspects and thus needs to be considered its own entity. First, a liver graft becomes the patient's primary metabolic regulator after liver transplantation, but this would not be the case for kidney or other grafts. The metabolic states, as well as the genetics of the graft, play crucial roles in the development of NODALT. Second, dysfunction of the islets of Langerhans is common in cirrhotic patients and would be exacerbated by immunosuppressive agents, particularly calcineurin inhibitors. On the other hand, minimized immunosuppressive protocols have been widely advocated in liver transplantation because of liver tolerance (immune privilege). Third and last, through the "gut-liver axis," graft function is closely linked to gut microbiota, which is now considered an important metabolic organ and known to independently influence the host's metabolic homeostasis. Liver transplant recipients present with specific gut microbiota that may be prone to trigger metabolic disorders. In this review, we proposed 3 possible sites for the origin of NODALT, which are liver, islets, and gut, to help elucidate the underlying mechanism of NODALT. 10.1097/TP.0000000000001111
    Could the beneficial effects of dietary calcium on obesity and diabetes control be mediated by changes in intestinal microbiota and integrity? Gomes J M G,Costa J A,Alfenas R C The British journal of nutrition Evidence from animal and human studies has associated gut microbiota, increased translocation of lipopolysaccharide (LPS) and reduced intestinal integrity (II) with the inflammatory state that occurs in obesity and type 2 diabetes mellitus (T2DM). Consumption of Ca may favour body weight reduction and glycaemic control, but its influence on II and gut microbiota is not well understood. Considering the impact of metabolic diseases on public health and the role of Ca on the pathophysiology of these diseases, this review critically discusses possible mechanisms by which high-Ca diets could affect gut microbiota and II. Published studies from 1993 to 2015 about this topic were searched and selected from Medline/PubMed, Scielo and Lilacs databases. High-Ca diets seem to favour the growth of lactobacilli, maintain II (especially in the colon), reduce translocation of LPS and regulate tight-junction gene expression. We conclude that dietary Ca might interfere with gut microbiota and II modulations and it can partly explain the effect of Ca on obesity and T2DM control. However, further research is required to define the supplementation period, the dose and the type of Ca supplement (milk or salt) required for more effective results. As Ca interacts with other components of the diet, these interactions must also be considered in future studies. We believe that more complex mechanisms involving extraintestinal disorders (hormones, cytokines and other biomarkers) also need to be studied. 10.1017/S0007114515003608
    Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes mellitus: focus on bile acid sequestrants. Holst Jens Juul,McGill Maria A Clinical drug investigation Type 2 diabetes mellitus is associated with a progressive decline in insulin-producing pancreatic β-cells, an increase in hepatic glucose production, and a decrease in insulin sensitivity. The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) stimulate glucose-induced insulin secretion; however, in patients with type 2 diabetes, the incretin system is impaired by loss of the insulinotropic effects of GIP as well as a possible reduction in secretion of GLP-1. Agents that modify GLP-1 secretion may have a role in the management of type 2 diabetes. The currently available incretin-based therapies, GLP-1 receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 (DPP-4) inhibitors (CD26 antigen inhibitors) [incretin enhancers], are safe and effective in the treatment of type 2 diabetes. However, they may be unable to halt the progression of type 2 diabetes, perhaps because they do not increase secretion of endogenous GLP-1. Therapies that directly target intestinal L cells to stimulate secretion of endogenous GLP-1 could possibly prove more effective than treatment with GLP-1 receptor agonists and DPP-4 inhibitors. Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes include G-protein-coupled receptor (GPCR) agonists, α-glucosidase inhibitors, peroxisome proliferator-activated receptor (PPAR) agonists, metformin, bile acid mimetics and bile acid sequestrants. Both the GPCR agonist AR231453 and the novel bile acid mimetic INT-777 have been shown to stimulate GLP-1 release, leading to increased insulin secretion and improved glucose tolerance in mice. Similarly, a study in insulin-resistant rats demonstrated that the bile acid sequestrant colesevelam increased GLP-1 secretion and improved glucose levels and insulin resistance. In addition, the bile acid sequestrant colestimide (colestilan) has been shown to increase GLP-1 secretion and decrease glucose levels in patients with type 2 diabetes; these results suggest that the glucose-lowering effects of bile acid sequestrants may be partly due to their ability to increase endogenous GLP-1 levels. Evidence suggests that GPCR agonists, α-glucosidase inhibitors, PPAR agonists, metformin, bile acid mimetics and bile acid sequestrants may represent a new approach to management of type 2 diabetes via modification of endogenous GLP-1 secretion. 10.2165/11595370-000000000-00000
    Impact of bariatric surgery on type 2 diabetes: contribution of inflammation and gut microbiome? Debédat Jean,Amouyal Chloé,Aron-Wisnewsky Judith,Clément Karine Seminars in immunopathology Obesity is a chronic low-grade inflammatory disease (both at the systemic and adipose tissue level) that continues to rise worldwide. It is associated with an abundance of comorbidities, including type 2 diabetes (T2D). Bariatric surgery, which induces modifications of the intestinal tract, is to date the most successful treatment for obesity. Its use has dramatically increased in number as it enables both weight reduction and metabolic improvements, with 60% of patients even achieving diabetes remission. Several mechanisms are actually demonstrated to be involved in those clinical improvements. Importantly, both obesity and T2D share many phenotypic characteristics, including increased systemic and adipose tissue inflammation, as well as gut microbiota dysbiosis. These characteristics are deeply modulated after bariatric surgery. This review will address the host metabolic changes observed after bariatric surgery, focusing on the induced gut architectural changes, as well as on the modifications of the inflammatory tone and the gut microbiota. 10.1007/s00281-019-00738-3
    Mechanisms in endocrinology: Gut microbiota in patients with type 2 diabetes mellitus. Allin Kristine H,Nielsen Trine,Pedersen Oluf European journal of endocrinology Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies on mice have demonstrated several underlying mechanisms including host signalling through bacterial lipopolysaccharides derived from the outer membranes of Gram-negative bacteria, bacterial fermentation of dietary fibres to short-chain fatty acids and bacterial modulation of bile acids. On top of this, an increased permeability of the intestinal epithelium may lead to increased absorption of macromolecules from the intestinal content resulting in systemic immune responses, low-grade inflammation and altered signalling pathways influencing lipid and glucose metabolism. While mechanistic studies on mice collectively support a causal role of the gut microbiota in metabolic diseases, the majority of studies in humans are correlative of nature and thus hinder causal inferences. Importantly, several factors known to influence the risk of type 2 diabetes, e.g. diet and age, have also been linked to alterations in the gut microbiota complicating the interpretation of correlative studies. However, based upon the available evidence, it is hypothesised that the gut microbiota may mediate or modulate the influence of lifestyle factors triggering development of type 2 diabetes. Thus, the aim of this review is to critically discuss the potential role of the gut microbiota in the pathophysiology and pathogenesis of type 2 diabetes. 10.1530/EJE-14-0874
    Comparative study of clinical features of patients with celiac disease & those with concurrent celiac disease & type 1 diabetes mellitus. Bhadada Sanjay Kumar,Rastogi Ashu,Agarwal Aakash,Kochhar Rashi,Kochhar Rakesh,Bhansali Anil The Indian journal of medical research BACKGROUND & OBJECTIVES:Celiac disease (CD) and type 1 diabetes mellitus (T1DM) share a common genetic locus and clinical manifestations. The present study was planned to compare clinical, biochemical and hormonal profiles of patients with CD and CD with T1DM. METHODS:Records of CD patients with age ≤20 yr, available anthropometric measurements, haematological, biochemical and hormonal workup with tissue transglutaminase IgA antibody and duodenal biopsy (Marsh grade) were screened. The patients were divided into two groups i.e., CD alone (Group A) and concurrent CD with T1DM (Group B). RESULTS:One hundred and nine patients of CD (57 male) with a mean age of 14.9±2.9 yr were evaluated. Of these, 86 (78.9%) patients had CD alone and 23 (13 females) (21.1%) patients had CD with T1DM. The age at diagnosis and the lag duration for the diagnosis of CD were 11.5±4.6 versus 13.8±3.4 yr (P<0.05) and 48.8 ±43.3 versus 20.2±31.8 months (P<0.05) in groups A and B, respectively. The most common histopathological grade was type 3b (59.2%) in group A and type 2 (42.1%) in group B. Short stature (87% vs. 40.9%; P<0.01), anaemia (80.9% vs. 45%, P<0.01) and delayed puberty (61.9% vs. 29.4%; P<0.01) were more common in group A. INTERPRETATION & CONCLUSIONS:Patients with CD alone have a longer lag time to diagnosis and consequent sequel in the form of anaemia, short stature and delayed puberty, as compared to patients with concurrent CD and T1DM. 10.4103/ijmr.IJMR_666_14
    Bile acids and their effects on diabetes. Rajani Cynthia,Jia Wei Frontiers of medicine Diabetes is a widespread, rapidly increasing metabolic disease that is driven by hyperglycemia. Early glycemic control is of primary importance to avoid vascular complications including development of retinal disorders leading to blindness, end-stage renal disease, and accelerated atherosclerosis with a higher risk of myocardial infarction, stroke and limb amputations. Even after hyperglycemia has been brought under control, "metabolic memory," a cluster of irreversible metabolic changes that allow diabetes to progress, may persist depending on the duration of hyperglycemia. Manipulation of bile acid (BA) receptors and the BA pool have been shown to be useful in establishing glycemic control in diabetes due to their ability to regulate energy metabolism by binding and activating nuclear transcription factors such as farnesoid X receptor (FXR) in liver and intestine as well as the G-protein coupled receptor, TGR5, in enteroendocrine cells and pancreatic β-cells. The downstream targets of BA activated FXR, FGF15/21, are also important for glucose/insulin homeostasis. In this review we will discuss the effect of BAs on glucose and lipid metabolism and explore recent research on establishing glycemic control in diabetes through the manipulation of BAs and their receptors in the liver, intestine and pancreas, alteration of the enterohepatic circulation, bariatric surgery and alignment of circadian rhythms. 10.1007/s11684-018-0644-x
    The role of the intestinal microbiota in type 1 diabetes. Hara Naoko,Alkanani Aimon K,Ir Diana,Robertson Charles E,Wagner Brandie D,Frank Daniel N,Zipris Danny Clinical immunology (Orlando, Fla.) The digestive tract hosts trillions of bacteria that interact with the immune system and can influence the balance between pro-inflammatory and regulatory immune responses. Recent studies suggest that alterations in the composition of the intestinal microbiota may be linked with the development of type 1 diabetes (T1D). Data from the biobreeding diabetes prone (BBDP) and the LEW1.WR1 models of T1D support the hypothesis that intestinal bacteria may be involved in early disease mechanisms. The data indicate that cross-talk between the gut microbiota and the innate immune system may be involved in islet destruction. Whether a causal link between intestinal microbiota and T1D exists, the identity of the bacteria and the mechanism whereby they promote the disease remain to be examined. A better understanding of the interplay between microbes and innate immune pathways in early disease stages holds promise for the design of immune interventions and disease prevention in genetically susceptible individuals. 10.1016/j.clim.2012.12.001
    Alterations of intestinal lipoprotein metabolism in diabetes mellitus and metabolic syndrome. Arca Marcello Atherosclerosis. Supplements Diabetes and metabolic syndrome are associated with abnormal postprandial lipoprotein metabolism, with a significant delay in the clearance of many lipid parameters, including triglycerides and chylomicrons. Abnormal concentrations of plasma lipids can result from changes in the production, conversion, or catabolism of lipoprotein particles. Whereas the liver is involved in controlling serum lipid levels through synthesis of liver derived triglyceride-rich lipoproteins and low-density lipoprotein metabolism, the intestine also has a major role in lipoprotein production. Postprandial lipemia results from increases in apoB-48 availability, lipogenesis, and the synthesis and absorption of cholesterol in the enterocytes. Increased intestinal lipoprotein production prolongs postprandial lipemia in patients with diabetes and MetS, and may contribute directly to atherogenesis in these patients. 10.1016/S1567-5688(15)50004-4
    IMPLICATION OF GUT MICROBIOTA IN DIABETES MELLITUS AND OBESITY. Grigorescu I,Dumitrascu D L Acta endocrinologica (Bucharest, Romania : 2005) Background and aims:Differences in the composition of the species of microorganisms in the gut may predict the evolution toward obesity and diabetes mellitus. We carried out a systematic review of the studies dedicated to the role of gut microbiota in diabetes mellitus and obesity. Methods:A systematic literature search of electronic databases was performed, using the search syntax: "Gut microbiota and diabetes and obesity"; abstracts in English, with data about mechanisms of pathogenesis and treatment options by changing the gut composition were included (259 articles). Studies were excluded if they did not have an abstract, or they contained no data about the exact implication mechanism of microbiota. Results:There are differences regarding the composition of the gut microbiota in healthy people and type 2 diabetes mellitus patients; the later proved to have significantly decreased Clostridium components, and increased Lactobacillus and Bifidobacterium populations.The intestines of obese subjects are less rich in microbial genes, have a reduced amount of Bacteroidetes and an increased amount of Firmicutes. Fecal microbiota transplantation from obese subjects resulted in adoption of the donor somatotype. Early differences in gut microbiota composition (higher number of Bifidobacteria) function as diagnostic markers for the development of type 2 diabetes mellitus in high-risk patients.The gut endotoxins contribute to metabolic syndrome manifestation. Experimental studies with prebiotic showed lower levels of cytokines and antiobesity potential. Conclusion:Microbiota composition and its changes since childhood have an important role in the metabolic syndrome. Any intervention in order to prevent or treat obesity and diabetes mellitus should have as target the gut immune system. 10.4183/aeb.2016.206
    Type 2 Diabetes Mellitus Is Associated with More Serious Small Intestinal Mucosal Injuries. Zhong Hao-Jie,Yuan Yu,Xie Wen-Rui,Chen Mei-Hui,He Xing-Xiang PloS one BACKGROUND:Clinical and experimental research has revealed that diabetes mellitus (DM) is characterized by intestinal hypomotility, gut microbial dysbiosis, increased gut permeability, microcirculation disorders, circulatory changes, and dysfunction of intestinal stem cells, which may be linked to inflammation of intestinal mucosa. However, the relationship between type 2 DM (T2DM) and macroscopic small intestinal mucosal injuries is still unclear. Therefore, we retrospectively studied capsule endoscopy data to determine the relationship between T2DM and small intestinal mucosal injuries. MATERIALS AND METHODS:We compared the records of 38 T2DM patients with those of 152 non-DM patients for small intestinal mucosal injuries. Different types of mucosal injuries and Lewis scores were compared between T2DM and non-DM patients. The relationships between patients with or without different types of diabetic complications and the Lewis score was assessed. Moreover, the relationships between insulin resistance and Lewis score, between HbA1c and Lewis score, were also both assessed. RESULTS:The prevalence of a villous edema in subjects with T2DM was significantly higher than in those without DM (P < 0.001), but incidence of ulcers was not different (P = 1.000). With T2DM, the Lewis score was also significantly higher (P = 0.002). In addition, subjects with diabetic nephropathy showed significantly higher Lewis scores than patients without diabetic nephropathy (P = 0.033). In Pearson's correlation tests, the homeostasis model assessment of insulin resistance (HOMA-IR) value was correlated positively with the Lewis score (γ = 0.175, P = 0.015), but no statistical correlation was found between HbA1c level and Lewis score (γ = 0.039, P = 0.697). CONCLUSIONS:Subjects with T2DM, especially those with diabetic nephropathy, have higher Lewis scores and more serious small intestinal mucosal lesions. 10.1371/journal.pone.0162354
    Effects of diabetes mellitus on myenteric neuronal density and sodium channel expression in the rat ileum. Brasileiro Amanda Damasceno,Garcia Lidiane Pereira,de Carvalho da Silva Samuel,Rocha Lenaldo Branco,Pedrosa André Luiz,Vieira André Shwambach,da Silva Valdo José Dias,Rodrigues Aldo Rogelis Aquiles Brain research Diabetes mellitus (DM) may lead to gastrointestinal motility disorders. Rodent models of DM indicate the presence of morpho-functional abnormalities of the enteric nervous system. Here, we evaluated whether experimental DM can cause changes in the excitatory cholinergic fibers, neuronal density, and voltage-gated sodium channel (Nav) expression in the myenteric plexus of the ileum. After streptozotocin-induced hyperglycemia in female rats progressed for eight weeks, triple immunofluorescence labeling experiments revealed that the neuronal density in DM rats was significantly lower than that in control. On average, the density of total neurons reduced by 52.2% (p = 0.0001), cholinergic neurons by 50.0% (p = 0.0068), and nitrergic neurons by 54.8% (p = 0.0042). The number of neurons per ganglionic area was also significantly reduced (to 28.2% of total neurons, p = 0.0002; 27.7% of cholinergic neurons, p = 0.0002, and 32.1% of nitrergic neurons, p = 0.0016). Furthermore, the density of the cholinergic fibers at the surface of the longitudinal muscle was significantly reduced (DM: 24 ± 3%; p = 0.003, control: 41 ± 2%); however, western-blot analysis did not indicate a reduction in the expression of choline acetyltransferase (ChAT) in the DM group. The Nav1.6 isoform was detected in different myenteric neurons of the ileum. RT-qPCR data did not suggest an alteration of transcripts for ChAT, neuronal nitric oxide synthase, Nav1.3, Nav1.6, or Nav1.7. Our data support the view that chronic DM leads to a reduction of excitatory cholinergic fibers and neuronal density. However, changes in sodium channel expression pattern, which could cause neuronal dysfunction, were not detected. 10.1016/j.brainres.2018.11.041
    [State of intestinal microbiota in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease]. Lytvynenko K O,Bodnar P M,Lysiana T O,Ponomar'ova I H,Koval'chuk O A Likars'ka sprava High prevalence of type 2 diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD) contributes to the intensification of scientific research the aim of which is to improve existing treatment. It is given the data about the state of intestinal microbiota in 64 patients with type 2 DM and NAFLD, 26 patients with type 2 DM and 28--with NAFLD. The research revealed significant changes in microbiota composition in patients with type 2 DM combined with NAFLD. Decompensated dysbiosis was registered in 71.9% of patients in this group which manifested in increased quantitative indicators of transient microflora crop with pathogenic characteristics and lack of microflora with protective characteristics.
    Enteric neuropathy associated to diabetes mellitus. Uranga-Ocio José Antonio,Bastús-Díez Sonia,Delkáder-Palacios Drissa,García-Cristóbal Noemí,Leal-García Miguel Ángel,Abalo-Delgado Raquel Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva Diabetes mellitus (DM) is a group of diseases highly prevalent nowadays. Its different types produce very similar symptoms with acute and chronic complications. Amongst these, gastrointestinal (GI) dysmotility, associated with the development of neuropathy in the enteric nervous system (ENS) is recognized. The objective is to review the current knowledge on GI dysmotility and enteric neuropathy associated to diabetes mellitus. The different functional and structural alterations within the digestive tract in diabetic patients and animal models are described. Finally, the therapeutic and preventive strategies tested so far in the context of enteric diabetic neuropathy are briefly summarized.In conclusion, amongst the alterations described in DM, the loss of inhibitory intrinsic innervation of the gut is most remarkable. Different therapeutic and/or preventive strategies, including the use of insulin, nerve growth factor or antioxidants, as well as myenteric neuron transplantation, are proposed.
    Type 2 diabetes mellitus as a risk factor for intestinal resection in patients with superior mesenteric vein thrombosis. Elkrief Laure,Corcos Olivier,Bruno Onorina,Larroque Beatrice,Rautou Pierre-Emmanuel,Zekrini Kamal,Bretagnol Frédéric,Joly Francisca,Francoz Claire,Bondjemah Vanessa,Cazals-Hatem Dominique,Boudaoud Larbi,De Raucourt Emmanuelle,Panis Yves,Goria Odile,Hillaire Sophie,Valla Dominique,Plessier Aurélie Liver international : official journal of the International Association for the Study of the Liver BACKGROUND & AIMS:The most serious complication of acute mesenteric vein thrombosis (MVT) is acute intestinal ischaemia requiring intestinal resection or causing death. Risk factors for this complication are unknown. To identify risk factors for severe intestinal ischaemia leading to intestinal resection in patients with acute MVT. METHODS:We retrospectively analysed consecutive patients seen between 2002 and 2012 with acute MVT in 2 specialized units. Patients with cirrhosis were excluded. We compared patients who required intestinal resection to patients who did not. RESULTS:Among 57 patients, a local risk factor was identified in 14 (24%) patients, oral contraceptive use in 16 (29%), and at least one or more other systemic prothrombotic condition in 25 (44%). Five (9%) patients had diabetes mellitus (DM), 33 (58%) had overweight or obesity, 9 (18%) had hypertriglyceridemia and 10 (19%) had arterial hypertension. Eleven patients (19%) underwent intestinal resection. DM was significantly associated with intestinal resection (P = 0.02) while local factors or prothrombotic conditions were not. Computed tomography (CT) scans performed at diagnosis found that occlusion of second order radicles of the superior mesenteric vein was more frequently observed in patients who underwent intestinal resection (P = 0.009). CONCLUSIONS:In acute MVT, patients with underlying DM have an increased risk of requiring intestinal resection. Neither local factors nor systemic prothrombotic conditions are associated with intestinal resection. When CT scan shows the preservation of second order radicles of the superior mesenteric vein, the risk of severe resection is low. 10.1111/liv.12386
    Obesity, diabetes, and the gut microbiome: an updated review. Singer-Englar Tahli,Barlow Gillian,Mathur Ruchi Expert review of gastroenterology & hepatology INTRODUCTION:Obesity and diabetes are two of the most prevalent health problems and leading causes of death globally. As research on the intestinal microbiome increases, so does our understanding of its intricate relationship to these diseases, although this has yet to be fully elucidated. Areas covered: This review evaluates the role of the gut microbiome in obesity and diabetes, including the influences of internal and environmental factors. Literature searches were performed using the keywords 'diabetes,' 'insulin resistance,' 'gut microbiome,' 'gut microbes,' 'obesity,' and 'weight gain.' Expert commentary: Highlights of recent research include new findings regarding the effects of caloric restriction, which expound the importance of diet in shaping the gut microbiome, and studies reinforcing the lasting implications of antibiotic use for diabetes and obesity, particularly repeated doses in early childhood. Mechanistically, interactions between the microbiome and the host innate immune system, mediated by TLR4-LPS signaling, have been shown to meditate the metabolic benefits of caloric restriction. Further, gut microbes haven now been shown to regulate oxygen availability via butyrate production, thus protecting against the proliferation of pathogens such as E. coli and Salmonella. However, many microbial metabolites remain unidentified and their roles in obesity and diabetes remain to be determined. 10.1080/17474124.2019.1543023
    Spatial variations in gut permeability are linked to type 1 diabetes development in non-obese diabetic mice. Joesten William C,Short Audrey H,Kennedy Michael A BMJ open diabetes research & care Objectives:To determine if spatial variations in gut permeability play a role in regulating type 1 diabetes (T1D) progression. Research design and methods:Spatially resolved duodenum, jejunum, ileum, and large intestine sections from end-stage T1D non-obese diabetic (NOD) mice were probed by immunohistochemistry to quantify zonulin levels as a measure of gut permeability in early-progressor and late-progressor NOD mice in comparison with non-progressor NOD mice and healthy NOR/LtJ control mice. Results:Zonulin levels were elevated in the small and large intestines in early-progressor and late-progressor NOD mice in comparison with non-progressor NOD mice and healthy NOR control mice. In early-onset mice, elevated zonulin levels were maximum in the duodenum and jejunum and decreased in the ileum and large intestine. In late-progressor mice, zonulin levels were elevated almost evenly along the small and large intestines. In non-progressor NOD mice, zonulin levels were comparable with NOR control levels in both the small and large intestines. Conclusions:Elevated zonulin expression levels indicated that gut permeability was increased both in the small and large intestines in NOD mice that progressed to end-stage T1D in comparison with non-progressor NOD mice and healthy NOR control mice. Highest elevations in zonulin levels were observed in the duodenum and jejunum followed by the ileum and large intestines. Spatial variations in gut permeability appeared to play a role in regulating the rate and severity of T1D progression in NOD mice indicating that spatial variations in gut permeability should be investigated as a potentially important factor in human T1D progression. 10.1136/bmjdrc-2019-000793
    Intestinal microbiota and faecal transplantation as treatment modality for insulin resistance and type 2 diabetes mellitus. Udayappan S D,Hartstra A V,Dallinga-Thie G M,Nieuwdorp M Clinical and experimental immunology The prevalence of obesity and diabetes mellitus type 2 is increasing rapidly around the globe. Recent insights have generated an entirely new perspective that the intestinal microbiota may play a significant role in the development of these metabolic disorders. Alterations in the intestinal microbiota composition promote systemic inflammation that is a hallmark of obesity and subsequent insulin resistance. Thus, it is important to understand the reciprocal relationship between intestinal microbiota composition and metabolic health in order to eventually prevent disease progression. In this respect, faecal transplantation studies have implicated that butyrate-producing intestinal bacteria are crucial in this process and be considered as key players in regulating diverse signalling cascades associated with human glucose and lipid metabolism. 10.1111/cei.12293
    Effects of probiotics in patients with diabetes mellitus type 2: study protocol for a randomized, double-blind, placebo-controlled trial. Alokail Majed S,Sabico Shaun,Al-Saleh Yousef,Al-Daghri Nasser M,Alkharfy Khalid M,Vanhoutte Paul M,McTernan Philip G Trials BACKGROUND:Low grade chronic inflammation is observed in patients with type 2 diabetes mellitus (T2DM). Endotoxin derived from gut bacteria may act as a potent inflammatory stimulant. Probiotics, which are believed to contain health promoting live microorganisms, may influence circulating endotoxin levels. Ingestion of live probiotic cultures may alter gut microbiota in a beneficial manner to reduce inflammation; no information is available whether or not they do so in patients with T2DM. Therefore, the aim of this study is to characterize the beneficial effects of probiotics on circulating endotoxin levels and other biomarkers related to systemic low-grade inflammation in patients with T2DM. METHODS:One hundred and twenty consenting adult Saudi T2DM patients (naïve or newly diagnosed and without co-morbidities) will be enrolled in this clinical trial and randomized to receive daily placebo or probiotics (Ecologic®Barrier) for 26 weeks in a double-blind manner. Inflammatory and metabolic markers will be measured and fecal samples analyzed. Measurements/samples will be obtained at baseline and after 4, 8, 12/13 and 26 weeks of treatment. DISCUSSION:It is expected that the probiotic product will induce beneficial changes in gut microbiota, reduce the systemic inflammatory state through altering systemic endotoxin levels and, as such, reduce the systemic inflammatory response observed in T2DM subjects. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT01765517. 10.1186/1745-6215-14-195
    Comparative investigation of in vitro biotransformation of 14 components in Ginkgo biloba extract in normal, diabetes and diabetic nephropathy rat intestinal bacteria matrix. Tang Daoquan,Yu Yanyan,Zheng Xiaoxiao,Wu Jing,Li Yinjie,Wu Xiaowen,Du Qian,Yin Xiaoxing Journal of pharmaceutical and biomedical analysis Most herbal medicines will be metabolized by intestinal bacteria in the gastrointestinal tract before absorbed by the small intestine. Ginkgo biloba extract (GBE) possesses protective effects on the glomerulosclerosis of diabetic nephropathy (DN), but its biotransformation in diabetes and DN intestinal bacteria has not yet been recognized. In this work, a validated liquid chromatography-tandem mass spectrometry (LC-MS) method was established for the simultaneous quantification of 14 components in GBE in rat intestinal bacteria matrix, namely ginkgolides A, ginkgolides B, ginkgolides C, bilobalide, rutin, myricetin, quercitrin, quercetin, luteolin, genistein, kaempferol, apigenin, isorhamnetin and genkwanin. Chromatographic separation was performed on a Kromasil-C18 (4.6mm×250mm i.d., 5.0μm) analytical column maintained at 35°C. The mobile phase was a mixture of methanol (A) and 0.1% formic acid in water (B) with a step linear gradient at a flow rate of 1.0mlmin(-1). The calibration curves of these 14 analytes demonstrated good linearity within the test range (R>0.99). This validated method has successfully been applied into the pharmacokinetic study of the 14 components. More importantly, in the pharmacokinetic study, by comparing the time course of the biotransformation by normal, diabetes and DN rat intestinal bacteria, we found that the biotransformation speed and residence time of the 14 compounds in diabetes and DN rats differed obviously from that obtained in normal group, which provided valuable chemical information for further pharmacology and active mechanism research on GBE. 10.1016/j.jpba.2014.07.022
    Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus. Li Jiang,Guo Qing-Jun,Cai Jin-Zhen,Pan Cheng,Shen Zhong-Yang,Jiang Wen-Tao World journal of gastroenterology Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM. 10.3748/wjg.v23.i45.8104
    Modulation of Type 1 Diabetes Risk by the Intestinal Microbiome. Knip Mikael,Honkanen Jarno Current diabetes reports PURPOSE OF REVIEW:The purpose of this review is to summarize potential modulations of the intestinal microbiome aimed at preventing or delaying progression to overt type 1 diabetes in the light of recently identified perturbations of the gut microbiota associated with the development of type 1 diabetes. RECENT FINDINGS:Accumulated data suggest that the gut microbiota is involved at two different steps in the evolution of type 1 diabetes. At the first step, the intestinal tract is colonized by a microbial community unable to provide an adequate education of the immune system. As a consequence, the infant acquires susceptibility to immune-mediated diseases, type 1 diabetes included. At the other step, the young child seroconverts to positivity for diabetes-associated autoantibodies. This is preceded or accompanied by a decrease in the diversity of the intestinal microbiota and an increased abundance of Bacteroides species. These changes will affect the disease process promoting progression toward overt type 1 diabetes. By providing specific probiotics, one can affect the colonization of the intestinal tract in the newborn infant or strengthen the immune education in early life. Human milk oligosaccharides function as nutrients for "healthy" bacteria. Dietary interventions applying modified starches can influence the numbers and activities of both autoreactive and regulatory T cells and provide protection against autoimmune diabetes in non-obese diabetic mice. Modulation of the intestinal microbiome holds the promise of effective protection against human type 1 diabetes. 10.1007/s11892-017-0933-9
    Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus. Zhang Lijing,Zhou Wen,Zhan Libin,Hou Shenglin,Zhao Chunyan,Bi Tingting,Lu Xiaoguang Aging Obesity is one of the susceptibility factors for type 2 diabetes (T2DM), both of which could accelerate the aging of the body and bring many hazards. A causal relationship is present between intestinal microbiota and body metabolism, but how the microbiota play a role in the progression of obesity to T2DM has not been elucidated. In this study, we transplanted healthy or obese-T2DM intestinal microbiota to ZDF and LZ rats, and used 16S rRNA and targeted metabonomics to evaluate the directional effect of the microbiota on the susceptibility of obese rats to T2DM. The glycolipid metabolism phenotype could be changed bidirectionally in obese rats instead of in lean ones. One possible mechanism is that the microbiota and metabolites alter the structure of the intestinal tract, and improve insulin and leptin resistance through JAK2 / IRS / Akt pathway. It is worth noting that 7 genera, such as , and can regulate 15 metabolites, such as 3-indolpropionic acid, acetic acid and docosahexaenoic acid, and have a significant improvement on glycolipid metabolism phenotype. Attention to intestinal homeostasis may be the key to controlling obesity and preventing T2DM. 10.18632/aging.103756
    [Role of the enterocyte in type 2 diabetes mellitus associated dyslipidemia]. Closs Cecilia I,Ruiz Diaz Martín A,Cafferata Alberto M,Becú-Villalobos Damasia,Nogueira Juan P Medicina In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.
    Type 1 diabetes mellitus: Complex interplay of oxidative stress, cytokines, gastrointestinal motility and small intestinal bacterial overgrowth. Malik Aastha,Morya Rajesh Kumar,Bhadada Sanjay Kumar,Rana Satyavati European journal of clinical investigation BACKGROUND:Oxidative stress is risk factor in progression of diabetes. It can increase cytokine production via several different mechanisms. Inflammation can affect gut neural apparatus that may lead to dysmotility which may exaggerate occurrence of bacterial overgrowth in intestine. Thus, a study was planned to understand the complex interplay of oxidative stress, inflammatory cytokines, gut motility and small intestinal bacterial overgrowth in type 1 diabetes mellitus (T1DM) patients. MATERIALS AND METHODS:Seventy-five T1DM patients and 75 healthy controls were enrolled. Small intestinal bacterial overgrowth (SIBO) and orocecal transit time (OCTT) were measured using noninvasive glucose and lactulose hydrogen breath tests, respectively. Plasma levels of interleukin-6 (IL-6), tissue necrosis factor-alfa (TNF-α) and interleukin-10 (IL-10) were measured in all subjects by ELISA. Oxidative stress and anti-oxidant parameters were measured by standard methods. RESULTS:Out of 75 T1DM patients, 36 were males with Mean ± SD age 22.3 ± 5.2 years, IL-6, TNF-α and IL-10 were significantly higher (P < 0.05) in T1DM patients as compared to controls. Lipid peroxidation (LPO) was significantly increased (P < 0.001), while reduced glutathione (GSH) significantly decreased (P < 0.01), whereas superoxide dismutase (SOD) and catalase significantly higher (P < 0.05) in T1DM patients as compared to controls. Positive correlation was observed between glycated haemoglobin (HbA1c) levels with LPO and negative correlation with GSH. Further, there was positive correlation between LPO and inflammatory cytokines (IL-6 & IL-10). OCTT was delayed and SIBO significantly higher in patients as compared to controls. On comparison of T1DM based on duration of disease, effect of all parameters was more pronounced in disease duration ≥5 years. CONCLUSION:This study indicates that there is association between hyperglycaemia, oxidative stress (LPO), anti-oxidants (GSH, SOD and catalase), inflammatory cytokines, gut motility (OCTT), and small intestinal overgrowth in type 1 diabetes mellitus patients. This association is intensified as duration of disease increases. 10.1111/eci.13021
    [Physiological patterns of intestinal microbiota. The role of dysbacteriosis in obesity, insulin resistance, diabetes and metabolic syndrome]. Halmos Tamás,Suba Ilona Orvosi hetilap The intestinal microbiota is well-known for a long time, but due to newly recognized functions, clinician's attention has turned to it again in the last decade. About 100 000 billion bacteria are present in the human intestines. The composition of bacteriota living in diverse parts of the intestinal tract is variable according to age, body weight, geological site, and diet as well. Normal bacteriota defend the organism against the penetration of harmful microorganisms, and has many other functions in the gut wall integrity, innate immunity, insulin sensitivity, metabolism, and it is in cross-talk with the brain functions as well. It's a recent recognition, that intestinal microbiota has a direct effect on the brain, and the brain also influences the microbiota. This two-way gut-brain axis consists of microbiota, immune and neuroendocrine system, as well as of the autonomic and central nervous system. Emerging from fermentation of carbohydrates, short-chain fatty acids develop into the intestines, which produce butyrates, acetates and propionates, having favorable effects on different metabolic processes. Composition of the intestinal microbiota is affected by the circadian rhythm, such as in shift workers. Dysruption of circadian rhythm may influence intestinal microbiota. The imbalance between the microbiota and host organism leads to dysbacteriosis. From the membrane of Gram-negative bacteria lipopolysacharides penetrate into the blood stream, via impaired permeability of the intestinal mucosa. These processes induce metabolic endotoxaemia, inflammation, impaired glucose metabolism, insulin resistance, obesity, and contribute to the development of metabolic syndrome, type 2 diabetes, inflammarory bowel diseases, autoimmunity and carcinogenesis. Encouraging therapeutic possibility is to restore the normal microbiota either using pro- or prebiotics, fecal transplantation or bariatric surgery. Human investigations seem to prove that fecal transplant from lean healthy individuals into obese diabetic patients improved all the pathological parameters. Wide spread use of bariatric surgery altered gut microbiota and improved metabolic parameters apart from surgery itself. Pathomechanism is not yet completely clarified. Clinicians hope, that deeper understanding of complex functions of intestinal microbiota will contribute to develop more effective therapeutic proceedings against diabetes, metabolic syndrome, and obesity. 10.1556/650.2015.30296
    Role of Gut Microbiota in Type 2 Diabetes Mellitus and Its Complications: Novel Insights and Potential Intervention Strategies. Woldeamlak Birhanu,Yirdaw Ketsela,Biadgo Belete The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi Type 2 diabetes mellitus has become one of the fastest growing public health problems worldwide. The disease is believed to involve a complex process involving genetic susceptibility and environmental factors. The human intestine harbors hundreds of trillions of bacteria, as well as bacteriophage particles, viruses, fungi, and archaea, which constitute a complex and dynamic ecosystem referred to as the gut microbiota. Increasing evidence has indicated changes in the gut microbiota composition or function in type 2 diabetic patients. An analysis of 'dysbiosis' enables the detection of alterations in the specific bacteria, clusters of bacteria, or bacterial functions associated with the occurrence of type 2 diabetes. These bacteria are involved predominantly in the control of inflammation and energy homeostasis. This review attempts to show that the gut microbiota are important factors for the occurrence of type 2 diabetes and are important for the treatment of gut microbiota dysbiosis through bariatric surgery, fecal microbiota transplantation, prebiotics, and probiotics. 10.4166/kjg.2019.74.6.314
    Role of the Gastrointestinal Tract Microbiome in the Pathophysiology of Diabetes Mellitus. Sohail Muhammad U,Althani Asmaa,Anwar Haseeb,Rizzi Roberto,Marei Hany E Journal of diabetes research The incidence of diabetes mellitus is rapidly increasing throughout the world. Although the exact cause of the disease is not fully clear, perhaps, genetics, ethnic origin, obesity, age, and lifestyle are considered as few of many contributory factors for the disease pathogenesis. In recent years, the disease progression is particularly linked with functional and taxonomic alterations in the gastrointestinal tract microbiome. A change in microbial diversity, referred as microbial dysbiosis, alters the gut fermentation profile and intestinal wall integrity and causes metabolic endotoxemia, low-grade inflammation, autoimmunity, and other affiliated metabolic disorders. This article aims to summarize the role of the gut microbiome in the pathogenesis of diabetes. Additionally, we summarize gut microbial dysbiosis in preclinical and clinical diabetes cases reported in literature in the recent years. 10.1155/2017/9631435