Microbiota-Immune Interaction in the Pathogenesis of Gut-Derived Infection.
Wang Chenyang,Li Qiurong,Ren Jianan
Frontiers in immunology
Gut-derived infection is among the most common complications in patients who underwent severe trauma, serious burn, major surgery, hemorrhagic shock or severe acute pancreatitis (SAP). It could cause sepsis and multiple organ dysfunction syndrome (MODS), which are regarded as a leading cause of mortality in these cases. Gut-derived infection is commonly caused by pathological translocation of intestinal bacteria or endotoxins, resulting from the dysfunction of the gut barrier. In the last decades, the studies regarding to the pathogenesis of gut-derived infection mainly focused on the breakdown of intestinal epithelial tight junction and increased permeability. Limited information is available on the roles of intestinal microbial barrier in the development of gut-derived infection. Recently, advances of next-generation DNA sequencing techniques and its utilization has revolutionized the gut microecology, leading to novel views into the composition of the intestinal microbiota and its connections with multiple diseases. Here, we reviewed the recent progress in the research field of intestinal barrier disruption and gut-derived infection, mainly through the perspectives of the dysbiosis of intestinal microbiota and its interaction with intestinal mucosal immune cells. This review presents novel insights into how the gut microbiota collaborates with mucosal immune cells to involve the development of pathological bacterial translocation. The data might have important implication to better understand the mechanism underlying pathological bacterial translocation, contributing us to develop new strategies for prevention and treatment of gut-derived sepsis.
Pulmonary Th17 Antifungal Immunity Is Regulated by the Gut Microbiome.
McAleer Jeremy P,Nguyen Nikki L H,Chen Kong,Kumar Pawan,Ricks David M,Binnie Matthew,Armentrout Rachel A,Pociask Derek A,Hein Aaron,Yu Amy,Vikram Amit,Bibby Kyle,Umesaki Yoshinori,Rivera Amariliz,Sheppard Dean,Ouyang Wenjun,Hooper Lora V,Kolls Jay K
Journal of immunology (Baltimore, Md. : 1950)
Commensal microbiota are critical for the development of local immune responses. In this article, we show that gut microbiota can regulate CD4 T cell polarization during pulmonary fungal infections. Vancomycin drinking water significantly decreased lung Th17 cell numbers during acute infection, demonstrating that Gram-positive commensals contribute to systemic inflammation. We next tested a role for RegIIIγ, an IL-22-inducible antimicrobial protein with specificity for Gram-positive bacteria. Following infection, increased accumulation of Th17 cells in the lungs of RegIIIγ(-/-) and Il22(-/-) mice was associated with intestinal segmented filamentous bacteria (SFB) colonization. Although gastrointestinal delivery of rRegIIIγ decreased lung inflammatory gene expression and protected Il22(-/-) mice from weight loss during infection, it had no direct effect on SFB colonization, fungal clearance, or lung Th17 immunity. We further show that vancomycin only decreased lung IL-17 production in mice colonized with SFB. To determine the link between gut microbiota and lung immunity, serum-transfer experiments revealed that IL-1R ligands increase the accumulation of lung Th17 cells. These data suggest that intestinal microbiota, including SFB, can regulate pulmonary adaptive immune responses.
Effects of rhubarb on intestinal flora and toll-like receptors of intestinal mucosa in rats with severe acute pancreatitis.
Yao Ping,Cui Min,Li Yan,Deng Yiyun,Wu Hao
OBJECTIVE:The aim of this study was to examine the effects of rhubarb on intestinal flora and toll-like receptors (TLRs) of intestinal mucosa in rats with severe acute pancreatitis (SAP). METHODS:Healthy male Sprague-Dawley rats were randomly allocated into sham-operated surgical model of SAP without or with postoperative rhubarb treatment groups (7 in each group). Rats in with rhubarb group received 10% rhubarb decoction (1 mL/200 g) through tube feeding at every 8 hours during postoperative 24 hours. Serum amylase, amount of intestinal flora, and TLR2/TLR4 messenger RNA expression in intestinal mucosa were tested among 3 groups at postoperative 24 hours. RESULTS:TLR2 and TLR4 messenger RNA expression levels in intestinal mucosa in SAP without rhubarb group were significantly higher than those in sham-operated or SAP with rhubarb groups (P < 0.05). The amount of intestinal lactobacilli and bifidobacteria in SAP without rhubarb group were significantly fewer than in those sham-operated group (P < 0.05) but not significantly different from those in SAP with rhubarb group (P > 0.05). The amount of intestinal Escherichia coli was relatively higher in SAP group than in sham-operated group (P > 0.05) but lesser in rhubarb treatment group (P > 0.05). CONCLUSIONS:Rhubarb might maintain the intestinal mucosal barrier through regulating intestinal flora and inhibiting intestinal inflammatory response in rats with SAP.
Alteration of the intestinal flora may participate in the development of Graves' disease: a study conducted among the Han population in southwest China.
Yang Mengxue,Sun Bowen,Li Jianhui,Yang Bo,Xu Jie,Zhou Xue,Yu Jie,Zhang Xuan,Zhang Qun,Zhou Shan,Sun Xiaohua
Objectives:The pathogenesis of Graves' disease (GD) remains unclear. In terms of environmental factors, GD development may be associated with chronic inflammation caused by alteration of the intestinal flora. This study explored the association of intestinal flora alteration with the development of GD among the Han population in southwest China. Design and methods:Fifteen GD patients at the Affiliated Hospital of Zunyi Medical College between March 2016 and March 2017 were randomly enrolled. Additionally, 15 sex- and age-matched healthy volunteers were selected as the control group during the same period. Fresh stool samples were collected, and bacterial 16S RNA was extracted and amplified for gene sequencing with the Illumina MiSeq platform. The sequencing results were subjected to operational taxonomic unit-based classification, classification verification, alpha diversity analysis, taxonomic composition analysis and partial least squares-discriminant analysis (PLS-DA). Results:The diversity indices for the GD group were lower than those for the control group. The GD group showed significantly higher abundances of Firmicutes, Proteobacteria and Actinobacillus and a higher Firmicutes/Bacteroidetes ratio than the control group. PLS-DA suggested the satisfactory classification of the flora between the GD group and the control group. The abundances of the genera Oribacterium, Mogibacterium, Lactobacillus, Aggregatibacter and Mogibacterium were significantly higher in the GD group than in the control group (P < 0.05). Conclusions:The intestinal flora of GD patients was significantly different from that of the healthy population. Thus, alteration of intestinal flora may be associated with the development of GD.
Study on the Antihypertensive Mechanism of and Based on Intestinal Flora-Host Metabolism.
Han Cong,Jiang Yue-Hua,Li Wei,Liu Yao,Qi Zhen-Qiang
Evidence-based complementary and alternative medicine : eCAM
Our previous studies have shown that the combination of and (HD) had a good antihypertensive effect, but its potential mechanism remained unclear. This study aimed to investigate the role of intestinal flora and serum metabolism induced by HD against hypertension. 16 spontaneous hypertensive rats (SHRs) were divided into HD group (5.9 g/kg) and model group (M) (normal saline), with eight Wistar-Kyoto (WKY) rats as control group (W) (normal saline). Rats were fed by gavage once a day for 28 days. The changes of intestinal flora and serum metabolism were analyzed by 16S rDNA sequencing and LC-MS/MS assay. HD decreased blood pressure steadily, improved the structure and composition of imbalance flora in SHRs, increased the abundance and diversity of flora, and decreased flora Firmicutes to Bacteroidetes (F/B) ratio. sp. increased remarkably in M group. and increased significantly in HD group, which were functionally related to the significant increase of , and in W group, which were all probiotics producing butyric acid, lactic acid, and regulating inflammation and other antihypertensive related factors. HD also changed the serum metabolic pattern of SHRs. 16 potential biomarkers related to inflammation, vasodilation, steroid hormones, oxidative stress, and etc. changed significantly, mainly enriched in arachidonic acid metabolism, tryptophan metabolism, steroid hormone biosynthesis, and glutathione metabolism. The correlation analysis demonstrated that the dominant genius and species in three groups were highly correlated with steroid hormone biosynthesis, arachidonic acid metabolism, tryptophan metabolism, and vitamin B6 metabolism. Our research indicated that HD had a good antihypertensive effect, which may be driven by the protective intestinal flora and beneficial metabolites induced by it, and the metabolites were closely related to the changes of intestinal flora. It provided new insights for the antihypertensive mechanism of HD.
Analysis of changes in intestinal flora and intravascular inflammation and coronary heart disease in obese patients.
Li Xv,Li Chuantao
Experimental and therapeutic medicine
Changes in intestinal flora in obese patients and intravascular C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and coronary heart disease (CHD) were analyzed. A total of 75 cases of obese patients were divided into obesity (OB) alone (n=40) and OB with CHD group (n=35). There was no statistically significant difference in age, sex, pre-existing basic diabetes, history of hypertension, and body mass index (P>0.05). Results showed that total bacterial load of CHD was obviously higher than that of OB group. The uric acid decomposed by intestinal flora (IFUA) and blood uric acid levels in CHD were higher than those in OB group, but the fecal uric acid level was lower than that of OB group (P<0.05). Levels of inflammatory factors in CHD, were significantly higher than those in OB group (P<0.05). Correlation analyses showed that the intestinal flora total load and CRP were positively correlated (r=0.793, P<0.001). Intestinal flora and Gensini score were also positively related to total load (r=0.893, P=0.893). Furthermore, CRP and Gensini score were positively related (r=0.796, P<0.796). IFUA and Gensini score were positively related to (r=0.647, P<0.001). Over-reaction in the flammation system in obese patients may lead to intestinal flora disorder, disturbance and also increased levels of IFUA and inflammatory factors.
Gastrointestinal microbiome and breast cancer: correlations, mechanisms and potential clinical implications.
Yang Jiqiao,Tan Qiuwen,Fu Qingyu,Zhou Yaojie,Hu Yuanyuan,Tang Shenli,Zhou Yuting,Zhang Junhui,Qiu Juanjuan,Lv Qing
Breast cancer (Tokyo, Japan)
Gastrointestinal microbiome plays as a symbiont which provides protection effect against invading pathogens, aids in the immune system development, nutrient reclamation and absorption as well as molecule breakdown. And it may avert carcinogenesis through these biological activities. By now, studies have been carried out to elaborate the association between gastrointestinal microbiome and breast cancer. It has been implicated that breast cancer was substantially associated with estrogen-dependent and estrogen-independent functions of gastrointestinal microbiome. Evidence from animal experiments also confirmed mammary tumor-related changes in microbial community. The possible mechanisms involve estrogen metabolism, immune regulation, obese status and so forth. Based on the current evidence, cues on future management strategies of breast cancer such as antibiotics and dietary interventions are proposed. In conclusion, large-scale clinical studies and bench-based researches are needed to validate the associations and elaborate the mechanisms, so as to reduce the risk of breast cancer and improve the outcomes of those already diagnosed.
The Gastrointestinal Microbiome: A Review.
Barko P C,McMichael M A,Swanson K S,Williams D A
Journal of veterinary internal medicine
The gastrointestinal microbiome is a diverse consortium of bacteria, archaea, fungi, protozoa, and viruses that inhabit the gut of all mammals. Studies in humans and other mammals have implicated the microbiome in a range of physiologic processes that are vital to host health including energy homeostasis, metabolism, gut epithelial health, immunologic activity, and neurobehavioral development. The microbial genome confers metabolic capabilities exceeding those of the host organism alone, making the gut microbiome an active participant in host physiology. Recent advances in DNA sequencing technology and computational biology have revolutionized the field of microbiomics, permitting mechanistic evaluation of the relationships between an animal and its microbial symbionts. Changes in the gastrointestinal microbiome are associated with diseases in humans and animals including inflammatory bowel disease, asthma, obesity, metabolic syndrome, cardiovascular disease, immune-mediated conditions, and neurodevelopmental conditions such as autism spectrum disorder. While there remains a paucity of data regarding the intestinal microbiome in small animals, recent studies have helped to characterize its role in host animal health and associated disease states. This review is intended to familiarize small animal veterinarians with recent advances in the field of microbiomics and to prime them for a future in which diagnostic tests and therapies will incorporate these developments into clinical practice.
Jlus66 extenuate oxidative stress and inflammation via regulation of intestinal flora in rats with non alcoholic fatty liver disease.
Wang Wei,Li Qian,Chai Wenhui,Sun Chunyan,Zhang Tiehua,Zhao Changhui,Yuan Yuan,Wang Xinyu,Liu Huiqin,Ye Haiqing
Food science & nutrition
The nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease that affects the health of people in an increasing rate. In the current research, we investigated the beneficial effect of a novel probiotic strain Jlus66 (Jlus66) on rats with high-fat diet (HFD)-induced NAFLD. The intestinal flora of rats was analyzed based on V3-V4 region 16S rDNA sequencing. Moreover, we measured the oxidative stress and inflammation factors in the liver using commercial ELISA kit, and the lipopolysaccharide (LPS) in serum with chromogenic end-point tachypheus amebocyte lysate. Compared with the HFD-induced group, Jlus66 treatment significantly decreased the malondialdehyde (MDA) level in the serum ( < 0.05). Additionally, Jlus66 significantly enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the liver and serum ( < 0.05). Jlus66 administration also reduced the levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), and inversely increased the interleukin-10 (IL-10) level in serum ( < 0.05). Intestinal flora analysis results showed that Jlus66 can improve intestinal flora structure by increasing the abundance of gram-positive flora such as Firmicutes, and decreasing gram-negative flora such as Bacteroidetes, Proteobacteria, and Fusobacteria, and then reduced LPS concentration in the serum. So we concluded that Jlus66 can improve NAFLD by modulating the intestinal flora and followed reduction of oxidative stress (OxS) and inflammation.
Vitamin A and Retinoic Acid Exhibit Protective Effects on Necrotizing Enterocolitis by Regulating Intestinal Flora and Enhancing the Intestinal Epithelial Barrier.
Xiao Sa,Li Qiuping,Hu Kun,He Yu,Ai Qing,Hu Liuhong,Yu Jialin
Archives of medical research
BACKGROUND:Exaggerated inflammation that characterizes necrotizing enterocolitis (NEC) is caused by the invasion of pathogens through an immature intestinal barrier. Vitamin A (VA) and retinoic acid (RA) play important roles in the growth of epithelial tissue and in modulating immune function. OBJECTIVE:To investigate the roles of VA and RA in the development of NEC. METHODS:Levels of serum retinol in patients and in a NEC mouse model were detected with high-performance liquid chromatography. Bacterial communities of NEC mice treated with VA or PBS were detected by high-throughput sequencing. In vitro and in vivo, levels of inflammatory factors were measured by ELISA and RT-PCR, and expression levels of claudin-1, occludin, and ZO-1 were detected by Western blotting. Transepithelial electrical resistance (TEER) was measured in Caco-2 cell monolayers. RESULTS:The level of VA in the NEC patients was lower than in the control patients. In the NEC mice that were treated with VA versus PBS, the proportion of Escherichia-Shigella was lower, while the abundance of Bacteroides was markedly higher. Both in vivo and in vitro, the levels of inflammatory factors were significantly reduced, while the expression levels of claudin-1, occludin, and ZO-1 were increased, after the VA and RA treatments. Meanwhile, TEER was increased and lipopolysaccharide-induced damage was reduced in Caco-2 cell monolayers after RA treatment. CONCLUSIONS:These results suggest that VA may regulate intestinal flora, alleviate inflammatory reactions, and enhance the intestinal epithelial barrier in NEC. Thus, VA may be an effective drug for providing protection against NEC in newborns.
Correlation between intestinal flora and serum inflammatory factors in patients with Crohn's disease.
Zhang J,Chen S-L,Li L-B
European review for medical and pharmacological sciences
OBJECTIVE:We investigated the correlation between intestinal flora and serum inflammatory factors in patients with Crohn's disease. PATIENTS AND METHODS:From February 2014 to June 2016, 132 patients with Crohn's were enrolled in this study. There were 84 males and 48 females. The age range was from 28 to 72 years. We had 62 patients in active stage (the activity group) and 70 patients in remission stage (the remission group). We also enrolled 71 healthy cases in the control group. The expression levels of serum inflammatory factors including IL-6, IL-17, IL-22, and IL-33 were measured using ELISA. Fresh feces samples were diluted and, after cultivating the bacteria for 48 hours at 37°C, the number of colonies was counted. The number of flora per gram of feces (CFU/g) was determined. RESULTS:The number of Escherichia coli and Enterococcus sp. in feces was significantly higher in the activity group compared to that of the control group and the remission group. The levels IL-1, IL-17, L-22, and IL-33 in the activity group were significantly higher than those of other groups. The number of Escherichia coli and Enterococcus sp. was positively correlated with the levels of IL-6, IL-17, IL-22, and IL-33, while the number of Bifidobacteria and Bacillus lactic acid was negatively correlated with the levels of IL-6, IL-17, IL-22, and IL-33. CONCLUSIONS:The number of conditional pathogenic bacteria in the activity group, was higher than other groups, while the number of probiotics bacteria decreased distinctly. We concluded that monitoring the changes in distribution and composition of intestinal flora as well as the levels of blood inflammatory factors could play a significant role in the treatment process of Crohn's disease.
Emerging trends and research foci in gastrointestinal microbiome.
Huang Xiaoquan,Fan Xiaowen,Ying Jun,Chen Shiyao
Journal of translational medicine
BACKGROUND:Gastrointestinal microbiome has drawn an increasing amount of attention over the past decades. There is emerging evidence that the gut flora plays a major role in the pathogenesis of certain diseases. We aimed to analyze the evolution of gastrointestinal microbiome research and evaluate publications qualitatively and quantitatively. METHODS:We obtained a record of 2891 manuscripts published between 1998 and 2018 from the Web of Science Core Collection (WoSCC) of Thomson Reuters; this record was obtained on June 23, 2018. The WoSCC is the most frequently used source of scientific information. We used the term "Gastrointestinal Microbiomes" and all of its hyponyms to retrieve the record, and restricted the subjects to gastroenterology and hepatology. We then derived a clustered network from 70,169 references that were cited by the 2891 manuscripts, and identified 676 top co-cited articles. Next, we used the bibliometric method, CiteSpace V, and VOSviewer 1.6.8 to identify top authors, journals, institutions, countries, keywords, co-cited articles, and trends. RESULTS:We identified that the number of publications on gastrointestinal microbiome is increasing over time. 112 journals published articles on gastrointestinal microbiome. The United States of America was the leading country for publications, and the leading institution was the University of North Carolina. Co-cited reference analysis revealed the top landmark articles in the field. Gut microbiota, inflammatory bowel disease (IBD), probiotics, irritable bowel disease, and obesity are some of the high frequency keywords in co-occurrence cluster analysis and co-cited reference cluster analysis; indicating gut microbiota and related digestive diseases remain the hotspots in gut microbiome research. Burst detection analysis of top keywords showed that bile acid, obesity, and Akkermansia muciniphila were the new research foci. CONCLUSIONS:This study revealed that our understanding of the link between gastrointestinal microbiome and associated diseases has evolved dramatically over time. The emerging new therapeutic targets in gut microbiota would be the foci of future research.
Intestinal Flora Disruption and Novel Biomarkers Associated With Nasopharyngeal Carcinoma.
Jiang Haiye,Li Jian,Zhang Bin,Huang Rong,Zhang Junhua,Chen Ziwei,Shang Xueling,Li Xisheng,Nie Xinmin
Frontiers in oncology
Nasopharyngeal carcinoma (NPC) is a malignant nasopharyngeal disease with a complicated etiology that occurs mostly in southern China. Intestinal flora imbalance is believed to be associated with a variety of organ malignancies. Current studies revealed that the destruction of intestinal flora is associated with NPC, and many studies have shown that intestinal flora can be used as a biomarker for many cancers and to predict cancer. To compare the differences in intestinal flora compositions and biological functions among 8 patients with familial NPC (NPC_F), 24 patients with sporadic NPC (NPC_S), and 27 healthy controls (NOR), we compared the intestinal flora DNA sequencing and hematological testing results between every two groups using bioinformatic methods. Compared to the NOR group, the intestinal flora structures of the patients in the NPC_F and NPC_S groups showed significant changes. In NPC_F, spp., spp., and spp. were significantly increased, and and spp. were significantly reduced. In NPC_S, , and spp. were significantly increased, and was significantly reduced. A beta diversity analysis showed significant difference compared NPC_F with NOR based on Bray Curtis ( = 0.012) and Unweighted UniFrac ( = 0.0045) index, respectively. The areas under the ROC curves plotted were all 1. Additionally, the concentrations of 5-hydroxytryptamine (5-HT) in NPC_F and NPC_S were significantly higher than those of NOR. was positively correlated with 5-HT (rcm: 0.85, < 0.001). A functional analysis of the intestinal flora showed that NPC_F was associated with Neurodegenerative Diseases ( = 0.023) and that NPC_S was associated with Neurodegenerative Diseases ( = 0.045) as well. We found that NPC was associated with structural imbalances in the intestinal flora, with that promoted the elevation of 5-HT and opportunistic pathogens being significantly increased, while probiotics significantly decreased. can be used as a novel biomarker and disease prediction models should be established for NPC. The new biomarkers and disease prediction models may be used for disease risk prediction and the screening of high-risk populations, as well as for the early noninvasive diagnosis of NPC.
[Incompatibility mechanism of Crotonis Semen Pulveratum and Glycyrrhizae Radix et Rhizoma based on diuretic effect and intestinal flora structure].
Li Yao,Guo Sheng,Tao Wei-Wei,Yu Jin-Gao,Su Shu-Lan,Duan Jin-Ao
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
Based on the toxic characteristics caused by the compatibility between "Zaoji Suiyuan" and Glycyrrhizae Radix et Rhizoma, which was found in the previous studies, the expanded study was carried out on the incompatibility mechanism between Crotonis Semen Pulveratum(CT) and Glycyrrhizae Radix et Rhizoma(GU) with the diuretic effect and intestinal flora as the characteristic indexes. The results showed that GU could slow down the rapid diuretic effect of CT, which suggested a tendency of decreasing the efficacy. Both the high and low dose of CT could significantly induce the intestinal injury and change the intestinal bacteria structure of mice. Low dose CT combined with GU could significantly increase the levels of Streptococcus and Rikenellaceae＿ukn. The relative abundance of Desulfovibrio and Streptococcaceae＿ukn were increased after the combined application of high dose CT and GU. It also suggested that there was a risk of inflammation in the liver and intestines when combined application of these two herbs. The results revealed that the combination of CT and GU has a tendency to reduce the clinical effect and increase the toxicity from the aspects of its traditional efficacy and its effect on intestinal microflora structure, which could provide the data for the clinical use of CT.
From the intestinal flora to the microbiome.
Sebastián Domingo Juan José,Sánchez Sánchez Clara
Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva
In this article, the history of the microbiota is reviewed and the related concepts of the microbiota, microbiome, metagenome, pathobiont, dysbiosis, holobiont, phylotype and enterotype are defined. The most precise and current knowledge about the microbiota is presented and the metabolic, nutritional and immunomodulatory functions are reviewed. Some gastrointestinal diseases whose pathogenesis is associated with the intestinal microbiota, including inflammatory bowel disease, irritable bowel syndrome and celiac disease, among others, are briefly discussed. Finally, some prominent and promising data with regard to the fecal microbiota transplantation in certain digestive illness are discussed.
The effect of fucoidan on intestinal flora and intestinal barrier function in rats with breast cancer.
Xue Meilan,Ji Xinqiang,Liang Hui,Liu Ying,Wang Bing,Sun Lingling,Li Weiwei
Food & function
Recent research studies have shown that the intestinal flora are related to the occurrence and progress of breast cancer. This study investigates the effect of fucoidan on intestinal flora and intestinal barrier function in rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancers. Sixty female Sprague-Dawley rats were randomly assigned to the control group, the model group, and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg per kg bw (body weight), respectively. Intestinal histopathological analysis was performed and 16S rDNA high-throughput sequencing was used to provide an overview of the intestinal flora composition. The contents of d-lactic acid (d-LA), diamine oxidase (DAO) and endotoxin in plasma were detected by ELISA. Expression levels of the tight junction (TJ) proteins, phosphorylated p38 MAPK and ERK1/2 were measured using western blotting. Our results suggested that the intestinal wall of the model group was damaged. However, after fucoidan intervention, the villi were gradually restored. ELISA showed that the levels of plasma endotoxin, d-LA and DAO decreased in the F1 and F2 groups compared to those in the model group. Fucoidan treatment also increased the expressions of ZO-1, occludin, claudin-1 and claudin-8. Furthermore, the expression levels of phosphorylated p38 MAPK and ERK1/2 were upregulated in fucoidan treatment groups. The results of 16S rDNA high-throughput sequencing indicated that fucoidan increased the diversity of the intestinal microbiota and induced changes in microbial composition, with the increased Bacteroidetes/Firmicutes phylum ratio. In conclusion, the supplement of fucoidan could improve the fecal microbiota composition and repair the intestinal barrier function. The study suggested the use of fucoidan as an intestinal flora modulator for potential prevention of breast cancer.
Effect and mechanism of vitamin D on the development of colorectal cancer based on intestinal flora disorder.
Zhou Xueyan,Chen Chunxia,Zhong Ya' Nan,Zhao Feng,Hao Zhixiang,Xu Yinxue,Lai Ran,Shen Guifang,Yin Xiaoxing
Journal of gastroenterology and hepatology
BACKGROUND:To investigate the correlation between the level of circulating vitamin D and the development of colorectal cancer (CRC) and to clarify the effect and mechanism of vitamin D on the development of CRC. METHODS:Serum samples from 63 patients with CRC (CRC group) and 61 healthy volunteers (normal group) were collected. Azoxymethane + dextran sodium sulfate-induced CRC mouse model and dietary models with different doses of vitamin D were established to verify whether vitamin D supplementation could reverse the occurrence and development of CRC at the overall animal level. Intestinal barrier integrity and microbial defense response were evaluated by detection of intestinal flora and expression of related genes. RESULTS:In the clinical serum samples, compared with the normal group, the level of 25 (OH) D3 in the CRC group was relatively low (P < 0.01), which was consistent with the clinical situation in mice. Vitamin D deficiency aggravated the deterioration of enteritis and intestinal cancer in CRC mice, whereas the overall condition of CRC mice improved after vitamin D supplementation. Vitamin D has a significant regulatory effect on the homeostasis of the intestinal flora, particularly in the regulation of intestinal probiotics, Akkermansia muciniphila-mediated colon barrier integrity. CONCLUSIONS:Vitamin D deficiency is closely related to the high incidence of CRC, and vitamin D supplementation can inhibit the occurrence and development of CRC. Vitamin D plays a role in the reversal of CRC mainly through the regulation of intestinal flora, especially the regulation of A. muciniphila-mediated colon barrier integrity.
CTGF-mediated ERK signaling pathway influences the inflammatory factors and intestinal flora in ulcerative colitis.
Song Zhen-Mei,Liu Fang,Chen Yan-Ming,Liu Yi-Jing,Wang Xiao-Di,Du Shi-Yu
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
OBJECTIVE:To examine the effect of connective tissue growth factor (CTGF)-mediated ERK signaling pathway on the inflammatory response and intestinal flora in ulcerative colitis (UC). METHODS:CTGF expression was determined through immunohistochemistry in UC and colon polyp patients. Dextran sulfate sodium (DSS) was used to construct UC models. Wild-type (WT) and CTGF-deficient (CTGF) mice were randomly divided into WT/CTGF + saline, WT/CTGF + DSS, and WT/CTGF + DSS + U0126 (ERK pathway inhibitor) groups. HE staining was conducted to observe the pathological changes in intestinal mucosa. The quantity of intestinal flora was tested in the feces. ELISA, qRT-PCR, and Western blotting were used to detect related-molecules expressions. RESULTS:CTGF was up-regulated in the intestinal mucosa of UC patients in relation to the severity and grade. Moreover, UC patients showed enhanced the expressions of p-ERK/ERK and pro-inflammatory factors (IL-1β, IL-6, TNF-α, MPO), increased the quantity of Bacteriodes fragilis (B. fragilis) and Escherichia coli (E. coli), and decreased Bifidobacterium and Lactobacillus. CTGF and pERK/ERK expressions were increased in DSS-induced WT mice, but the pERK expression was lower in CTGF + DSS group than that in the WT + DSS group. U0126 decreased the expressions of pro-inflammatory factors and improved the intestinal flora in WT mice induced with DSS. No significant differences were found in the above indexes between CTGF + DSS group and WT + DSS + U0126 group. CONCLUSION:Inhibiting CTGF could improve inflammatory response and intestinal flora to partially reverse DSS-induced UC via blocking ERK signaling pathway.
[Structural features of intestinal flora in preterm rats with cognitive impairment: an analysis based on high-thorough sequencing].
Yue Tao,Lu Hong-Yan,Xue Zheng-Yang,Xu Su-Qing,Tang Wei
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics
OBJECTIVE:To study the structural features of intestinal flora in preterm rats with cognitive impairment and the association of the change in intestinal flora with cognitive impairment in preterm rats. METHODS:Sprague-Dawley rats at 16-17 days of gestation were intraperitoneally injected with lipopolysaccharide for two consecutive days to establish a model of cognitive impairment, and the rats treated with intraperitoneally injected phosphate-buffered saline were established as the control group. Cesarean section was performed on day 21 of gestation, and preterm rats were randomly assigned to healthy maternal rats for feeding. The place navigation test in the Morris water maze was used to evaluate cognition on day 30 after birth. According to the result, the preterm rats were divided into cognitive impairment group with 21 rats and normal control group with 10 rats. Hematoxylin and eosin staining was used to observe pathological changes of the hippocampus, and fecal samples were collected for 16S rRNA sequencing and analysis. A principal component analysis (PCA) was performed for intestinal flora. RESULTS:Compared with the normal control group, the cognitive impairment group showed degeneration and necrosis of a large number of neurons in the hippocampus. Compared with the normal control group, the cognitive impairment group had significant reductions in the abundance and diversity of intestinal flora (P<0.05), with a significant increase in the abundance of Proteobacteria at the phylum level (P<0.05), as well as significant reductions in the abundance of Prevotella and Lactobacillus and significant increases in the abundance of Staphylococcaceae and Oligella at the order, family, and genus levels (P<0.05). PCA showed a significant difference in the composition of intestinal flora between the two groups. CONCLUSIONS:There is a significant change in the structure of intestinal flora in preterm rats with cognitive impairment, which provides a basis for the treatment and intervention of microecological changes due to cognitive impairment after preterm birth.
A study of the correlation between obesity and intestinal flora in school-age children.
Gao Xiaolin,Jia Ruizhen,Xie Liang,Kuang Linghan,Feng Ling,Wan Chaomin
With the improvement of living standards and dietary changes, childhood obesity has increased worldwide. This study aimed to understand the differences of intestinal flora structure between obese and normal children at school-age. Using the next generation sequencing platform, Illumina Miseq, 16S rDNA high-throughput sequencing technology, we analyzed the diversity and relative abundance of intestinal flora in 39 obese and 38 normal control school-age children. First, we categorized gut bacteria on the basis of their Operational taxonomic units (OTUs) using the RDP 16s rRNA database in RDP classifier. The alpha (α) diversity was used to measure the diversity within a sample and is calculated as a value for each sample. The beta (β) diversity was used to compare different samples and to measure the dissimilarity between each other sample. Our results indicated that intestinal flora in obese children showed lower diversity than normal controls. Significant differences of relative abundance of intestinal flora were detected at multiple levels of classifications. Identification of intestinal flora with significant difference between obese and normal children may provide important information to uncover the roles of these specific bacteria in the development of obesity and find new strategy to prevent and treat obesity through intervening the intestinal flora.
[Possibility of acupuncture treatment of ischemic stroke via regulating intestinal flora-immune response].
Ma Ji-Hong,Peng Yong-Jun,Sun Jian-Hua,Zhu Bing-Mei
Zhen ci yan jiu = Acupuncture research
At present, intestinal flora has attracted more and more attention from scholars in China and foreign countries, and its association with ischemic stroke (IS) has gradually become a new research hotspot in the field of stroke. Studies also showed that intestinal flora may be a risk factor which directly or indirectly affects the occurrence and development of IS through bacterial metabolites and immune activities. In the present paper, we review the positive effect of acupuncture and moxibustion in alleviating the symptoms of limb locomotor, speech, swallowing dysfunction, cognition, etc. to improve the IS patients' daily life ability and in strengthening the cellular immune function of the body. In addition, acupuncture and moxibustion have a positive effect in regulating intestinal flora and immune inflammation. Hence, in the present paper, we discuss their relationship and the possibility of application of acupuncture and moxibustion therapies to the treatment of IS according to the theory of "intestinal flora-immune response". It is thus reasonable to speculate that acupuncture and moxibustion can be used to promote the recovery of brain tissue injury and neurological function after stroke via correcting intestinal flora disturbance and reducing immune inflammatory response. In-depth exploration of the role of "intestinal flora-immune response" in the treatment of IS and the specific regulatory function of acupuncture and moxibustion will provide new ideas and research approaches to reveal their mechanisms in the treatment of stroke from a new perspective.
Research progress in the relationship between type 2 diabetes mellitus and intestinal flora.
Ma Quantao,Li Yaqi,Li Pengfei,Wang Min,Wang Jingkang,Tang Ziyan,Wang Ting,Luo Linglong,Wang Chunguo,Wang Ting,Zhao Baosheng
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Type 2 diabetes mellitus (T2DM) is a common clinical chronic disease, while its pathogenesis is still inconclusive. Intestinal flora, the largest micro-ecological system in the human body, is involved in, meanwhile has a major impact on the body's material and energy metabolism. Recent studies have shown that in addition to obesity, genetics, and islet dysfunction, the disturbance of intestinal flora may partly give rise to diabetes. In this paper, we summarized the current research on the correlation between T2DM and intestinal flora, and concluded the pathological mechanisms of intestinal flora involved in T2DM. Moreover, the ideas and methods of prevention and treatment of T2DM based on intestinal flora were proposed, providing theoretical basis and literature reference for the treatment of T2DM and its complications based on the regulation of intestinal flora.
Pathological Relationship between Intestinal Flora and Osteoarthritis and Intervention Mechanism of Chinese Medicine.
Wu Yong-Rong,Kuang Gao-Yan,Lu Fang-Guo,Wang Heng-Xin,Lu Min,Zhou Qing
Chinese journal of integrative medicine
Chinese medicine (CM) has a good clinical effect on osteoarthritis (OA), but the mechanism is not very clear. Evidence-based medicine researches have shown that intestinal flora plays a role in the pathogenesis and succession of OA. Intestinal flora affects the efficacy of CM, and CM can affect the balance of intestinal flora. This paper focuses on the relationship between intestinal flora, intestinal microenvironment, brain-gut axis, metabolic immunity and OA, and preliminarily expound the significance of intestinal flora in the pathogenesis of OA and the mechanism of CM intervention. The above discussion will be of great significance in the prevention and treatment of OA by CM from the perspective of intestinal flora.
Alteration of Intestinal Flora Stimulates Pulmonary microRNAs to Interfere with Host Antiviral Immunity in Influenza.
Pang Peng,Yu Bin,Shi Yucong,Deng Li,Xu Huachong,Wu Sizhi,Chen Xiaoyin
Molecules (Basel, Switzerland)
The intestinal flora may be an important and modifiable factor that contributes to the immune response in influenza. To investigate the effect of intestinal flora alteration induced by antibiotic interference on microRNA (miRNA) communication in antiviral immunity, BALB/c mice received two weeks of antibiotic treatment before infection with the influenza A virus. The changes in intestinal flora and pulmonary flora were detected and analyzed by 16S ribosomal RNA (rRNA) gene sequencing. The amplification of the influenza virus in the lungs was measured by RT-PCR. The involvement of pulmonary miRNA was explored using miRNA microarray analysis. The results showed that the antibiotics destroyed the symbiotic relationship of the intestinal flora, resulting in a reduction in bacterial diversity, but they did not affect the pulmonary flora. The alteration of intestinal flora affected the expression of pulmonary miRNAs and resulted in an enhancement of pulmonary influenza virus amplification. The conclusion is that alteration of intestinal flora induced by antibiotic interference affected the expression of pulmonary miRNAs to interfere with host antiviral immunity, of which miR-146b and miR-29c might be good resources of resistance to influenza under antibiotic abuse.
Correlations of Inflammatory Factors with Intestinal Flora and Gastrointestinal Incommensurate Symptoms in Children with Asthma.
Zhang Yixing,Li Tao,Yuan Huiqiang,Pan Wei,Dai Qigang
Medical science monitor : international medical journal of experimental and clinical research
BACKGROUND Bronchial asthma is a common pediatric disease, the pathogenesis of which is complicated. The correlations of the levels of inflammatory factors in peripheral serum with intestinal flora and gastrointestinal incommensurate symptoms in children with asthma remain to be further elucidated. MATERIAL AND METHODS A total of 70 children diagnosed with asthma in the Pediatric Department of our hospital from February 2016 to March 2017 were enrolled as an observation group, and another 25 healthy children in the same age range were selected as a control group. The levels of inflammatory factors [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)], the total load of intestinal flora, and the main strains were detected among all included patients. Moreover, incommensurate symptoms of patients in the observation group were recorded and gastrointestinal symptom rating scale (GSRS) scores were calculated. The differences in indexes between the observation group and the control group were compared. RESULTS The levels of CRP, TNF-α, and IL-6 in peripheral serum in the observation group were significantly higher than those in the control group (p<0.05). The analysis of the correlations of inflammatory factors in peripheral serum with intestinal flora and GSRS scores showed that C-reactive protein (CRP) was positively correlated with GSRS scores (r=0.696, p<0.001) and the total load of intestinal bacteria (r=0.813, p<0.001). CONCLUSIONS The inflammatory factors in peripheral serum of children with asthma are closely correlated with intestinal flora and gastrointestinal function. With the increasingly high levels of inflammatory factors in peripheral serum, the probability of intestinal flora disturbance and gastrointestinal incommensurate symptoms will be increased.
[Bacterial resistance influences intestinal flora and host immune regulation].
Gao Yanyu,Bi Wenjing,Wu Xinyan,Zhu Xiao,Luo Yi
Sheng wu gong cheng xue bao = Chinese journal of biotechnology
Overuse of antibiotics in aquaculture, husbandry and healthcare has led to antibiotics residues in the enviuronment and the generation of antibiotic resistant bacteria that can be transferred into the human gut through food chain. Based on literatures, we reviewed the influence of bacterial resistance on intestinal flora and related immune regulation. Taking the source of antibiotic resistance to human intestinal flora as an entry point, we addressed the structure of human intestinal flora and the composition of drug resistance genes after exposure to pollutants. Moreover, we discussed the relationship among changes of intestinal flora, antibiotic resistance genes and immunomodulation related diseases. Last, we also indicated future research needs.
Correlation analysis of intestinal flora with hypertension.
Liu Jilun,An Ning,Ma Cong,Li Xiaofeng,Zhang Jie,Zhu Wei,Zhang Yihe,Li Junpeng
Experimental and therapeutic medicine
Relationship between intestinal flora content and hypertension was investigated. Ninety-four patients with hypertension who were admitted and treated in No. 215 Hospital of Shaanxi Nuclear Industry from May 2016 to April 2017 were selected as the observation group; and 94 healthy people from the physical examination center of No. 215 Hospital of Shaanxi Nuclear Industry in the same time period were selected as the control group. The systolic (SBP) and diastolic blood pressure (DBP) of all the participants were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the quantities of and in the intestines, and correlation analyses were performed. The SBP, DBP and content of in the observation group were significantly higher than those in the control group, while the contents of and were obviously lower than those in the control group (P<0.05). Pearson's correlation analysis showed that was positively correlated with SBP and DBP, while and had a negative correlation with SBP and DBP (P<0.05). The results showed that the quantities of and are decreased while the number of is increased in the intestines of patients with hypertension. Moreover, the content of intestinal flora has a significant correlation with hypertension.
Emerging role of lncRNAs in the normal and diseased intestinal barrier.
Chen Jie,Wan Jianhua,Ye Jianfang,Xia Liang,Lu Nonghua
Inflammation research : official journal of the European Histamine Research Society ... [et al.]
OBJECTIVE:A significant effort has been made to understand the intestinal barrier, but the effective means to prevent, reduce, and restore intestinal mucosal damage remains unclear. Recently, a few of studies have explained the mechanism of the intestinal barrier in long noncoding RNAs (lncRNAs). This review aims to summarize recent views on the function of lncRNAs in the intestinal barrier and discuss the emerging role of lncRNAs in intestinal barrier diseases caused by inflammatory diseases. METHODS:Observations led us to believe that lncRNAs participate in inflammatory responses, cell proliferation, and control microbial susceptibility. In view of these, lncRNAs have been proved to involve in the intestinal barrier. RESULTS:lncRNAs directly or indirectly affect TJ mRNA translation and intestinal epithelial cells (IECs) paracellular permeability, as well as IECs proliferation and susceptibility to apoptosis, to modulate the function of the intestinal barrier. miRNAs play a pivotal role in this process. CONCLUSIONS:lncRNAs have been shown to be fundamentally involved in intestinal mucosal regeneration, protection, and epithelial barrier function. It may emerge as new and potential factors to be evaluated in the intestinal barrier diseases caused by acute pancreatitis, inflammatory bowel diseases, and imbalance of intestinal flora.
The characteristics analysis of intestinal microecology on cerebral infarction patients and its correlation with apolipoprotein E.
Wang Wenyue,Li Xu,Yao Xiuhua,Cheng Xiuli,Zhu Yu
Cerebral infarction (CI) is associated with high rates of disability, mortality, and death in China, but its mechanism is unclear. Therefore, early diagnosis of CI and determining its mechanism are very important. Intestinal microecology is thought to be related to cardiovascular and cerebrovascular diseases. We hypothesized that intestinal microecology is also related to CI and that the intestinal microecology in the stool of CI patients differs from that in healthy people.Fecal samples of healthy subjects and CI patient (all n = 10) and we investigated the intestinal microecology of CI patient and healthy people stool by 16 seconds sequencing and analyzed relative abundance and diversity of microorganisms by unweighted pair-group method with arithmetic mean analysis (UPGMA) and principal co-ordinates analysis (PCoA). We also measured apolipoprotein E (ApoE) levels in the serum by ELISA assay and analyzed the correlation between ApoE and intestinal flora.We found that the relative structure and diversity of intestinal microecology was significantly different between the stools of CI patients and healthy people. At the class level, Gammaproteobacteria was increased and Bacteroidia was decreased in CI patient stool. We found a correlation between ApoE in the serum and Bacteroidia and Gammaproteobacteria species.We considered the intestinal flora can be used as an indicator of CI and the up-regulation of ApoE may be the potential mediate for intestinal microecology contribute to CI.
Gut microbiota and aging.
Mangiola F,Nicoletti A,Gasbarrini A,Ponziani F R
European review for medical and pharmacological sciences
The hypothesis of an important role of gut microbiota in maintaining physiological state into the gastrointestinal (GI) system is supported by qualitative and quantitative alteration of the intestinal flora in a number of physiological and pathological condition as shown in several studies. The evidence of the inflammatory state alteration, highlighted in neurodegenerative diseases such as Parkinson's and Alzheimer's strongly recalls the microbiota disturbance, highly suggesting a link between the gastrointestinal system and cognitive functions. Given this perspective, looking at the mutual influence between microbiota products, inflammation mediators and immune system, the modulation of gut microbiota may help to facilitate a physiological and non-pathological aging process and, perhaps, to contrast the progression of degenerating mechanisms. Some studies have already characterized gut microbiota in elderly, with promising results. Future studies should be designed to better understand the correlation between the gut microbiota, the ageing process and degenerative diseases typical of the elderly.
An Interleukin-23-Interleukin-22 Axis Regulates Intestinal Microbial Homeostasis to Protect from Diet-Induced Atherosclerosis.
Fatkhullina Aliia R,Peshkova Iuliia O,Dzutsev Amiran,Aghayev Turan,McCulloch John A,Thovarai Vishal,Badger Jonathan H,Vats Ravi,Sundd Prithu,Tang Hsin-Yao,Kossenkov Andrew V,Hazen Stanley L,Trinchieri Giorgio,Grivennikov Sergei I,Koltsova Ekaterina K
Although commensal flora is involved in the regulation of immunity, the interplay between cytokine signaling and microbiota in atherosclerosis remains unknown. We found that interleukin (IL)-23 and its downstream target IL-22 restricted atherosclerosis by repressing pro-atherogenic microbiota. Inactivation of IL-23-IL-22 signaling led to deterioration of the intestinal barrier, dysbiosis, and expansion of pathogenic bacteria with distinct biosynthetic and metabolic properties, causing systemic increase in pro-atherogenic metabolites such as lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO). Augmented disease in the absence of the IL-23-IL-22 pathway was mediated in part by pro-atherogenic osteopontin, controlled by microbial metabolites. Microbiota transfer from IL-23-deficient mice accelerated atherosclerosis, whereas microbial depletion or IL-22 supplementation reduced inflammation and ameliorated disease. Our work uncovers the IL-23-IL-22 signaling as a regulator of atherosclerosis that restrains expansion of pro-atherogenic microbiota and argues for informed use of cytokine blockers to avoid cardiovascular side effects driven by microbiota and inflammation.
Correlation of liver function with intestinal flora, vitamin deficiency and IL-17A in patients with liver cirrhosis.
Mou Haijuan,Yang Fengying,Zhou Jianqin,Bao Cuixia
Experimental and therapeutic medicine
The aim of this study was to investigate the correlation of liver function, intestinal flora, vitamin D and interleukin-17A (IL-17A) levels in patients with liver cirrhosis. A total of 52 patients diagnosed with posthepatitic cirrhosis and admitted into Yantai Infectious Disease Hospital (Yantai, China) from January to December in 2012 (liver cirrhosis group), and 52 patients with chronic hepatitis B (hepatitis group), and 40 healthy volunteers receiving physical examination in the hospital (normal control group) were selected into the study. The liver function, hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, intestinal flora distribution, vitamin D and IL-17A levels of all patients were detected, and the correlation among them was analyzed via Pearson's analysis. The number of and in hepatitis and liver cirrhosis groups was significantly greater than in the normal control group (P<0.05), but the number of and was significantly decreased (P<0.05); the serum IL-17A levels in hepatitis and liver cirrhosis were obviously higher than that in the normal control group (P<0.05), but the serum vitamin D 25(OH) D and 1,25(OH)2D levels were obviously lower than that in the normal control group (P<0.05). In patients with liver cirrhosis, Enterobacteriaceae was positively correlated with prothrombin time (PT), was positively correlated with alanine aminotransferase and aspartate aminotransferase (AST) levels, was negatively correlated with AST, alkline phosphatase (AKP) and HBV DNA levels, and was negatively correlated with AST level and PT. There was a significant negative correlation between serum IL-17A and total bilirubin in patients with liver cirrhosis, and 25(OH) D was negatively correlated with AST, AKP and HBV DNA levels. In patients with liver cirrhosis, there was significant positive correlation between and IL-17A, and between and 25(OH)D, but other bacteria were not obviously associated with IL-17A and vitamin D. Intestinal flora imbalance, vitamin D deficiency and IL-17A imbalance play an important role in the evolution of liver cirrhosis.
Alzheimer's disease and gut microbiota modifications: The long way between preclinical studies and clinical evidence.
Mancuso Cesare,Santangelo Rosaria
Recent studies have suggested the role of an infectious component in the pathogenesis of Alzheimer's disease (AD). In light of this, research has focused on some bacteria constituting the intestinal microbial flora which can produce amyloid. Once generated, the latter hypothetically triggers a systemic inflammatory response which compromises complex brain functions, such as learning and memory. Clinical studies have shown that, in cognitively impaired elderly patients with brain amyloidosis, there is lower abundance in the gut of E. rectale and B. fragilis, two bacterial species which have an anti-inflammatory activity, versus a greater amount of pro-inflammatory genera such as Escherichia/Shigella. According to these findings, some clinical studies have demonstrated that supplementation with Lactobacilli- and Bifidobacteria- based probiotics has improved cognitive, sensory and emotional functions in subjects with AD. Moreover, certain herbal products, in particular dietetic polyphenols, have proved capable of restoring dysbiosis and, therefore, their prebiotic role could be effective in counteracting the onset of AD regardless of their activity of free radical scavenging or enhancement of the cell stress response. One of the recent greatest novelties in the field of neurodegenerative diseases is the chance to prevent or slow down AD progression with agents, such as probiotics and prebiotics, acting outside the central nervous system.
Myocardial infarction and gut microbiota: An incidental connection.
Zununi Vahed Sepideh,Barzegari Abolfazl,Zuluaga Marisol,Letourneur Didier,Pavon-Djavid Graciela
Myocardial infarction (MI) is the main cause of cardiovascular crises that entails serious concerns in mortality, morbidity, and cost to the society. The main therapeutic goal of modern cardiology is to develop novel approaches to minimize inflammation, myocardial necrosis/apoptosis, and enhance cardiac repair after MI. Though MI can be affected by genetic and environmental factors, the search for targeting lifestyle factors has been of greater interest. One such potential factor is the microbiota, the human intestinal microbial community. Although the fundamental data on the role of microbiome on MI is more limited, the disruption of intestinal flora structure provokes MI and poor prognosis. Since gut microbiota is readily modifiable through a variety of interventions, it can be targeted to modulate the host signaling pathways involved in inflammation and MI pathogenesis. Symbiosis bacteria can reduce ischemia/reperfusion injury and inflammation; moreover, they can regulate lipid metabolism, blood pressure, apoptosis, MI size, and overall cardiac survival. In this review, we provide an overview of the development of MI following the dysbiosis microbiota and give an update on a microbiota-based therapeutic strategy to delay or prevent MI.
Gene expression profiling of the mouse gut: Effect of intestinal flora on intestinal health.
Zhu Wenhua,Li Jun,Wu Benyan
Molecular medicine reports
The present study aimed to investigate the molecular mechanisms, including potential genes, pathways and interactions, underlying the effect of intestinal flora on intestinal health. The gene expression profiles of GSE22648 were downloaded from the Gene Expression Omnibus database to screen differentially expressed genes (DEGs). The Database for Annotation, Visualization and Integrated Discovery was used for Gene Ontology (GO) functional and pathway enrichment analysis of the DEGs. DEG‑associated literature was mined using the GenCLip 2.0 online tool. Finally, GO and pathway enrichment analyses of the DEGs in the literature were processed. By comparing microbiota‑depleted mouse samples and control mouse samples, a total of 115 DEGs, including 58 upregulated genes and 57 downregulated genes, were screened. The upregulated genes were enriched into various GO terms, including microsome, oxidation reduction and heme binding, whereas the 57 downregulated DEGs were enriched in different functions, including DNA packaging and linoleic acid metabolism. A total of 19 genes, including baculoviral IAP repeat containing 5, aurora kinase A, angiotensin I converting enzyme 2 and free fatty acid receptor 2 were identified and enriched in four modules, including cell division, chromosome segregation, inflammatory bowel disease and inflammatory response. AURKA, inner centromere protein antigens 135/155 kDa, baculoviral IAP repeat containing 5, aurora kinase B and solute carrier family 22 (organic cation/zwitterion transporter) member 4 were identified as potential important genes for intestinal flora and intestinal disease treatment through their involvement in various functions, including cell division, chromosome segregation, inflammatory bowel disease and inflammatory response.
Chronic glucocorticoid treatment induced circadian clock disorder leads to lipid metabolism and gut microbiota alterations in rats.
Wu Tao,Yang Luna,Jiang Jianguo,Ni Yinhua,Zhu Jiawei,Zheng Xiaojun,Wang Qi,Lu Xin,Fu Zhengwei
AIM:Glucocorticoids (GCs), steroid hormones synthetized by the adrenal gland, are regulated by circadian cycles, and dysregulation of GC signaling can lead to the development of metabolic syndrome. The effects and potential mechanism of GCs in physiology were investigated in the present study. MAIN METHODS:Male Wistar rats were orally administered dexamethasone sodium phosphate (DEX, 0.01 and 0.05mg/kg body weight per day) for 7weeks. KEY FINDING:DEX treatment attenuated body weight gain and reduced food intake, whereas it induced the accumulation of fat. Administration of DEX induced dysregulation of the expression of lipogenic genes in both fat and liver. Moreover, the mRNA levels of genes related to mitochondrial biogenesis and function were significantly downregulated in the liver and fat of DEX-treated rats. Furthermore, DEX treatment caused a significant reduction in the richness and diversity of the microbiota in the colon, as assessed using high-throughput sequencing of the 16s rRNA gene V3-V4 region, an increase in inflammatory cell infiltration, and a decrease in mucus secretion in the colon. Additionally, DEX administration induced phase shift or loss of circadian rhythmicity of clock-related genes in peripheral tissues. These results were associated with higher serum corticosterone levels and upregulation of GC receptor (GR) expression in peripheral tissues. SIGNIFICANCE:Our findings indicate that long-term administration of GC caused lipid accumulation, changes in the structure of the intestinal flora, and reduced colonic mucus secretion in vivo. The mechanism of these physiological changes may involve a circadian rhythm disorder and dysregulation of GR expression.
Relationship between intestinal flora and inflammatory factors in patients with nonalcoholic steatohepatitis.
Zhang Jian,Wang Chunying,Wang Ji,Zhang Fengchi
Experimental and therapeutic medicine
This study was conducted to analyze the change in intestinal flora of patients with nonalcoholic steatohepatitis and its correlation to the levels of the inflammatory cytokines interleukin-10 (IL-10) and IL-17. We selected 90 patients that were diagnosed with and treated for nonalcoholic steatohepatitis as the patient group and 80 healthy cases as the control group. We then compared the intestinal flora in the subject feces and the intestinal colonization resistance (B/E, to ) of both groups. Using RT-PCR, we also detected IL-10 and IL-17 mRNA levels in the peripheral blood mononuclear cells of both groups. Furthermore, we used the ELISA method to determine serum IL-10 and IL-17 levels in order to explore the correlation between IL-10, IL-17 and B/E. The number of and were significantly lower in the patient group than the control group (P<0.05), while and pathogenic bacteria were significantly higher in the patient group than the control group (P<0.05). The B/E value was lower in the patient group than the control group (P<0.05). The relative expression of IL-10 and IL-17 mRNA in the patient group was significantly higher than in the control group (P<0.05). In the patient group, the serum IL-10 levels were 1.17±0.15 pg/ml, which is significantly higher than the control group serum IL-10 levels which were 0.32±0.04 pg/ml (P<0.05). The serum IL-17 levels in the patient groups were 0.96±0.11 pg/ml, which was significantly higher than the control group, which had an average of 0.28±0.01 pg/ml serum IL-17 levels (P<0.05). Pearson's correlation analysis showed that the change of B/E value of intestinal flora in the patients group were negatively correlated with serum IL-10 (r=-0.546, P<0.05), and negatively correlated with serum IL-17 (r=-0.535, P<0.05). Therefore, compared to healthy people, the expression of IL-10 and IL-17 in the peripheral blood of patients with non-alcoholic fatty liver is high. The changes in intestinal flora in patients with nonalcoholic steatohepatitis are closely related to the changes of serum IL-10 and IL-17 levels, and they are involved in the development of nonalcoholic steatohepatitis.