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    Gut microbiota and vitamin status in persons with obesity: A key interplay. Voland Lise,Le Roy Tiphaine,Debédat Jean,Clément Karine Obesity reviews : an official journal of the International Association for the Study of Obesity There are numerous factors involved in obesity progression and maintenance including systemic low-grade inflammation, adipose tissue dysfunction, or gut microbiota dysbiosis. Recently, a growing interest has arisen for vitamins' role in obesity and related disorders, both at the host and gut bacterial level. Indeed, vitamins are provided mostly by food, but some, from the B and K groups in particular, can be synthesized by the gut bacterial ecosystem and absorbed in the colon. Knowing that vitamin deficiency can alter many important cellular functions and lead to serious health issues, it is important to carefully monitor the vitamin status of patients with obesity and potentially already existing comorbidities as well as to examine the dysbiotic gut microbiota and thus potentially altered bacterial metabolism of vitamins. In this review, we examined both murine and human studies, to assess the prevalence of sub-optimal levels of several vitamins in obesity and metabolic alterations. This review also examines the relationship between vitamins and the gut microbiota in terms of vitamin production and the modulation of the gut bacterial ecosystem in conditions of vitamin shortage or supplementation. Furthermore, some strategies to improve vitamin status of patients with severe obesity are proposed within this review. 10.1111/obr.13377
    Obesity status and obesity-associated gut dysbiosis effects on hypothalamic structural covariance. Contreras-Rodriguez O,Arnoriaga-Rodríguez M,Miranda-Olivos R,Blasco G,Biarnés C,Puig J,Rivera-Pinto J,Calle M L,Pérez-Brocal V,Moya A,Coll C,Ramió-Torrentà L,Soriano-Mas C,Fernandez-Real J M International journal of obesity (2005) BACKGROUND:Functional connectivity alterations in the lateral and medial hypothalamic networks have been associated with the development and maintenance of obesity, but the possible impact on the structural properties of these networks remains largely unexplored. Also, obesity-related gut dysbiosis may delineate specific hypothalamic alterations within obese conditions. We aim to assess the effects of obesity, and obesity and gut-dysbiosis on the structural covariance differences in hypothalamic networks, executive functioning, and depressive symptoms. METHODS:Medial (MH) and lateral (LH) hypothalamic structural covariance alterations were identified in 57 subjects with obesity compared to 47 subjects without obesity. Gut dysbiosis in the subjects with obesity was defined by the presence of high (n = 28) and low (n = 29) values in a BMI-associated microbial signature, and posthoc comparisons between these groups were used as a proxy to explore the role of obesity-related gut dysbiosis on the hypothalamic measurements, executive function, and depressive symptoms. RESULTS:Structural covariance alterations between the MH and the striatum, lateral prefrontal, cingulate, insula, and temporal cortices are congruent with previously functional connectivity disruptions in obesity conditions. MH structural covariance decreases encompassed postcentral parietal cortices in the subjects with obesity and gut-dysbiosis, but increases with subcortical nuclei involved in the coding food-related hedonic information in the subjects with obesity without gut-dysbiosis. Alterations for the structural covariance of the LH in the subjects with obesity and gut-dysbiosis encompassed increases with frontolimbic networks, but decreases with the lateral orbitofrontal cortex in the subjects with obesity without gut-dysbiosis. Subjects with obesity and gut dysbiosis showed higher executive dysfunction and depressive symptoms. CONCLUSIONS:Obesity-related gut dysbiosis is linked to specific structural covariance alterations in hypothalamic networks relevant to the integration of somatic-visceral information, and emotion regulation. 10.1038/s41366-021-00953-9
    Age-related compositional changes and correlations of gut microbiome, serum metabolome, and immune factor in rats. Zhang Xia,Yang Yuping,Su Juan,Zheng Xiaojiao,Wang Chongchong,Chen Shaoqiu,Liu Jiajian,Lv Yingfang,Fan Shihao,Zhao Aihua,Chen Tianlu,Jia Wei,Wang Xiaoyan GeroScience Aging is a complex physiological process associated with degenerative disorder of metabolism and immune function, which contributes to the occurrence of senile diseases. The gut microbiota affects systemic inflammation in aging processes probably through metabolism, but their relationship is still unclear. In this study, 16S-rRNA-sequencing technology, gas chromatography-time-of-flight mass spectrometry (GC-TOFMS)-based metabolic profiling, and immune factor analysis combined with advanced differential and association analysis were employed to investigate the correlation between the microbiome, metabolome, and immune factors in male Wistar rats across lifespan. Our findings showed significant changes in the ileum microbiome and serum metabolome compositions across aging process. A two-level strategy was applied to demonstrate that key metabolites associated with age such as 4-hydroxyproline, proline, and lysine were clustered together and positively correlated with beneficial microbes including Bifidobacterium, Lactobacillus, and Akkermansia. Function analysis explored association between serum metabolite class and specific gut bacteria's metabolism pathways. Further correlation analysis on all the alteration patterns provided an interaction network of main immune factors such as IL-10, IgA, IgM, and IgG with key gut bacteria and serum metabolites. This study offers new insights into the relationship between immune factors, serum metabolome, and the gut microbiome. 10.1007/s11357-020-00188-y
    The gut microbiota as an environmental factor that regulates fat storage. Bäckhed Fredrik,Ding Hao,Wang Ting,Hooper Lora V,Koh Gou Young,Nagy Andras,Semenkovich Clay F,Gordon Jeffrey I Proceedings of the National Academy of Sciences of the United States of America New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1-/- animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host. Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AY 667702--AY 668946). 10.1073/pnas.0407076101
    Understanding the Role of the Gut Microbiome and Microbial Metabolites in Obesity and Obesity-Associated Metabolic Disorders: Current Evidence and Perspectives. Vallianou Natalia,Stratigou Theodora,Christodoulatos Gerasimos Socrates,Dalamaga Maria Current obesity reports PURPOSE:In this review, we summarize current evidence on the gut microbiome and microbial metabolites in relation to obesity and obesity-associated metabolic disorders. Special emphasis is given on mechanisms interconnecting gut microbiome and microbial metabolites with metabolic disorders as well as on potential preventive and therapeutic perspectives with a "bench to bedside" approach. RECENT FINDINGS:Recent data have highlighted the role of gut dysbiosis in the etiology and pathogenesis of metabolic disorders, including obesity, metabolic syndrome, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Overall, most studies have demonstrated a reduction in gut microbiome diversity and richness in obese subjects, but there is still much debate on the exact microbial signature of a healthy or an obese gut microbiome. Despite the controversial role of an altered gut microbiome as a cause or consequence of obesity in human studies, numerous animal studies and certain human studies suggest beneficial metabolic effects of certain microbial intestinal metabolites, such as butyrate, that could be used in the prevention and treatment of obesity and its comorbidities. More randomized controlled trials and larger prospective studies including well-defined cohorts as well as a multi-omics approach are warranted to better identify the associations between the gut microbiome, microbial metabolites, and obesity and its metabolic complications. 10.1007/s13679-019-00352-2
    Gut Microbiota Dysbiosis in Human Obesity: Impact of Bariatric Surgery. Debédat Jean,Clément Karine,Aron-Wisnewsky Judith Current obesity reports PURPOSE OF REVIEW:In this review, we summarize what is currently described in terms of gut microbiota (GM) dysbiosis modification post-bariatric surgery (BS) and their link with BS-induced clinical improvement. We also discuss how the major inter-individual variability in terms of GM changes could impact the clinical improvements seen in patients. RECENT FINDINGS:The persisting increase in severe obesity prevalence has led to the subsequent burst in BS number. Indeed, it is to date the best treatment option to induce major and sustainable weight loss and metabolic improvement in these patients. During obesity, the gut microbiota displays distinctive features such as low microbial gene richness and compositional and functional alterations (termed dysbiosis) which have been associated with low-grade inflammation, increased body weight and fat mass, as well as type-2 diabetes. Interestingly, GM changes post-BS is currently being proposed as one the many mechanism explaining BS beneficial clinical outcomes. BS enables partial rescue of GM dysbiosis observed during obesity. Some of the GM characteristics modified post-BS (composition in terms of bacteria and functions) are linked to BS beneficial outcomes such as weight loss or metabolic improvements. Nevertheless, the changes in GM post-BS display major variability from one patient to the other. As such, further large sample size studies associated with GM transfer studies in animals are still needed to completely decipher the role of GM in the clinical improvements observed post-surgery. 10.1007/s13679-019-00351-3
    Gut microbial metabolites in obesity, NAFLD and T2DM. Canfora Emanuel E,Meex Ruth C R,Venema Koen,Blaak Ellen E Nature reviews. Endocrinology Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved. 10.1038/s41574-019-0156-z
    Diet, Gut Microbiota, and Obesity: Links with Host Genetics and Epigenetics and Potential Applications. Cuevas-Sierra Amanda,Ramos-Lopez Omar,Riezu-Boj Jose I,Milagro Fermin I,Martinez J Alfredo Advances in nutrition (Bethesda, Md.) Diverse evidence suggests that the gut microbiota is involved in the development of obesity and associated comorbidities. It has been reported that the composition of the gut microbiota differs in obese and lean subjects, suggesting that microbiota dysbiosis can contribute to changes in body weight. However, the mechanisms by which the gut microbiota participates in energy homeostasis are unclear. Gut microbiota can be modulated positively or negatively by different lifestyle and dietary factors. Interestingly, complex interactions between genetic background, gut microbiota, and diet have also been reported concerning the risk of developing obesity and metabolic syndrome features. Moreover, microbial metabolites can induce epigenetic modifications (i.e., changes in DNA methylation and micro-RNA expression), with potential implications for health status and susceptibility to obesity. Also, microbial products, such as short-chain fatty acids or membrane proteins, may affect host metabolism by regulating appetite, lipogenesis, gluconeogenesis, inflammation, and other functions. Metabolomic approaches are being used to identify new postbiotics with biological activity in the host, allowing discovery of new targets and tools for incorporation into personalized therapies. This review summarizes the current understanding of the relations between the human gut microbiota and the onset and development of obesity. These scientific insights are paving the way to understanding the complex relation between obesity and microbiota. Among novel approaches, prebiotics, probiotics, postbiotics, and fecal microbiome transplantation could be useful to restore gut dysbiosis. 10.1093/advances/nmy078
    Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Meslier Victoria,Laiola Manolo,Roager Henrik Munch,De Filippis Francesca,Roume Hugo,Quinquis Benoit,Giacco Rosalba,Mennella Ilario,Ferracane Rosalia,Pons Nicolas,Pasolli Edoardo,Rivellese Angela,Dragsted Lars Ove,Vitaglione Paola,Ehrlich Stanislav Dusko,Ercolini Danilo Gut OBJECTIVES:This study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease. DESIGN:Eighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period. RESULTS:Increased MD adherence in the MedD group successfully reprogrammed subjects' intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa. CONCLUSION:Switching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health. 10.1136/gutjnl-2019-320438
    Lactobacillus alleviated obesity induced by high-fat diet in mice. Song Wei,Song Chen,Li Li,Wang Tianyi,Hu Jinhong,Zhu Lina,Yue Tianli Journal of food science Obesity is closely related to dyslipidaemia, diabetes and other metabolic syndromes. Long-term consumption of a high-fat diet (HFD) is an important risk factor that can lead to obesity. In the current research, three Lactobacillus strains, namely, Loigolactobacillus coryniformis subsp. torquens T3 (T3), Lacticasebacillus paracasei subsp. paracasei M5 (M5), and Lacticaseibacillus paracasei subsp. paracasei X12 (X12), were tested to determine their inhibitory effects on HFD-induced obesity. The results showed that M5, T3, and X12 significantly decreased the body weight gain, Lee's index and adipose index. T3 showed significant effects on reducing serum TG levels to 0.92 mmol/ml and increasing HDL-C levels to 2.18 mmol/ml. The M5 treatment significantly reduced the serum TG level and leptin content to 1.11 mmol/ml and 3.7 ng/ml, respectively, and it increased the HDL-C level and adiponectin content to 2.35 mmol/ml and 7 ng/ml, respectively. M5 and T3 dramatically ameliorated hepatic steatosis in HFD-treated mice by reducing the liver index, lipid droplet number in the liver and TC levels in the liver. Gene expression of PPAR-γ and TNF-α was notably downregulated and FAS was upregulated by T3 and M5 treatment. Additionally, administration of M5 and T3 modified the diversity of the gut microbiota with increased OTU number, ACE index, and Chao1, and decreased the Shannon index and the Bacteroidetes /Firmicutes ratio. Overall, our results indicate that Lactobacillus may be used to prevent obesity and gut dysbiosis. PRACTICAL APPLICATION: Lactobacillus from traditional Chinese foods showed strong anti-obesity effects on high-fat diet-fed mice through the regulation of adipocytokines. Additionally, administration of certain Lactobacilli modified the diversity of the gut microbiota. The results indicate that Lactobacillus may be promising functional materials in healthy foods. 10.1111/1750-3841.15971
    Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota. Palleja Albert,Kashani Alireza,Allin Kristine H,Nielsen Trine,Zhang Chenchen,Li Yin,Brach Thorsten,Liang Suisha,Feng Qiang,Jørgensen Nils Bruun,Bojsen-Møller Kirstine N,Dirksen Carsten,Burgdorf Kristoffer S,Holst Jens J,Madsbad Sten,Wang Jun,Pedersen Oluf,Hansen Torben,Arumugam Manimozhiyan Genome medicine BACKGROUND:Roux-en-Y gastric bypass (RYGB) is an effective means to achieve sustained weight loss for morbidly obese individuals. Besides rapid weight reduction, patients achieve major improvements of insulin sensitivity and glucose homeostasis. Dysbiosis of gut microbiota has been associated with obesity and some of its co-morbidities, like type 2 diabetes, and major changes of gut microbial communities have been hypothesized to mediate part of the beneficial metabolic effects observed after RYGB. Here we describe changes in gut microbial taxonomic composition and functional potential following RYGB. METHODS:We recruited 13 morbidly obese patients who underwent RYGB, carefully phenotyped them, and had their gut microbiomes quantified before (n = 13) and 3 months (n = 12) and 12 months (n = 8) after RYGB. Following shotgun metagenomic sequencing of the fecal microbial DNA purified from stools, we characterized the gut microbial composition at species and gene levels followed by functional annotation. RESULTS:In parallel with the weight loss and metabolic improvements, gut microbial diversity increased within the first 3 months after RYGB and remained high 1 year later. RYGB led to altered relative abundances of 31 species (P < 0.05, q < 0.15) within the first 3 months, including those of Escherichia coli, Klebsiella pneumoniae, Veillonella spp., Streptococcus spp., Alistipes spp., and Akkermansia muciniphila. Sixteen of these species maintained their altered relative abundances during the following 9 months. Interestingly, Faecalibacterium prausnitzii was the only species that decreased in relative abundance. Fifty-three microbial functional modules increased their relative abundance between baseline and 3 months (P < 0.05, q < 0.17). These functional changes included increased potential (i) to assimilate multiple energy sources using transporters and phosphotransferase systems, (ii) to use aerobic respiration, (iii) to shift from protein degradation to putrefaction, and (iv) to use amino acids and fatty acids as energy sources. CONCLUSIONS:Within 3 months after morbidly obese individuals had undergone RYGB, their gut microbiota featured an increased diversity, an altered composition, an increased potential for oxygen tolerance, and an increased potential for microbial utilization of macro- and micro-nutrients. These changes were maintained for the first year post-RYGB. TRIAL REGISTRATION:Current controlled trials (ID NCT00810823 , NCT01579981 , and NCT01993511 ). 10.1186/s13073-016-0312-1
    Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 modulate gene expression of subset specific transcription factors and cytokines in peripheral blood mononuclear cells of obese and overweight people. Zarrati Mitra,Shidfar Farzad,Nourijelyani Keramat,Mofid Vahid,Hossein zadeh-Attar Mohammad Javad,Bidad Katayoon,Najafi Forouzan,Gheflati Zahra,Chamari Maryam,Salehi Eisa BioFactors (Oxford, England) Probiotics are believed to have interaction with immune cells through sustained effects on gene expression of different cytokines and transcription factors. The present randomized doubled-blind controlled clinical trial was performed recruiting 75 individuals with BMI 25-35, who were randomly assigned to the following three groups: Group 1 (n = 25) who consumed regular yogurt as part of a low calorie diet [RLCD], group 2 (n = 25) who received probiotic yogurt with a LCD [PLCD] and group 3 (n = 25) who consumed probiotic yogurt without LCD [PWLCD] for 8 week. Participants in PLCD and PWLCD groups received 200 g/day yogurt containing Lactobacillus acidophilus La5, Bifidobacterium Bb12, and lactobacillus casei DN001 10(8) cfu/gr. The expression of the FOXP3, T-bet, GATA3, TNF-α, IFN-γ, TGF-β, and ROR-γt in PBMCs genes were assessed, before and after intervention. In three groups, ROR-γt expression was reduced (P = 0.007) and FOXP3 was increased (P < 0.001). The expression of TNFα, TGFβ, and GATA3 genes did not change among all groups after intervention. Interestingly, the expression of T-bet gene, which was significantly decreased in PLCD and PWLCD groups (P < 0.001), whereas gene expression of IFN-γ decreased in all three groups. Our results suggest that weight loss diet and probiotic yogurt had synergistic effects on T-cell subset specific gene expression in peripheral blood mononuclear cells among overweight and obese individuals. 10.1002/biof.1128
    Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption. Damms-Machado Antje,Mitra Suparna,Schollenberger Asja E,Kramer Klaus Michael,Meile Tobias,Königsrainer Alfred,Huson Daniel H,Bischoff Stephan C BioMed research international Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction. Laparoscopic sleeve gastrectomy (LSG), a surgical intervention for obesity, is classified as predominantly restrictive procedure. In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects (n = 5 per group) demonstrating identical weight loss during a follow-up period of six months. For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics. The energy-reabsorbing potential of the gut microbiota decreased following LSG, indicated by the Bacteroidetes/Firmicutes ratio, but increased during diet. Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups. No alteration of faecal butyrate was observed, but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention. LSG resulted in enhanced faecal excretion of nonesterified fatty acids and bile acids. LSG, but not dietetic restriction, improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype. Moreover, LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation. This trial is registered with ClinicalTrials.gov NCT01344525. 10.1155/2015/806248
    Time-restricted feeding induces Lactobacillus- and Akkermansia-specific functional changes in the rat fecal microbiota. NPJ biofilms and microbiomes Diet is a key factor influencing gut microbiota (GM) composition and functions, which in turn affect host health. Among dietary regimens, time-restricted (TR) feeding has been associated to numerous health benefits. The impact of TR feeding on the GM composition has been mostly explored by means of metagenomic sequencing. To date, however, little is known about the modulation of GM functions by this dietary regimen. Here, we analyzed the effects of TR feeding on GM functions by evaluating protein expression changes in a rat model through a metaproteomic approach. We observed that TR feeding has a relevant impact on GM functions, specifically leading to an increased abundance of several enzymes involved in carbohydrate and protein metabolism and expressed by Lactobacillus spp. and Akkermansia muciniphila. Taken together, these results contribute to deepening our knowledge about the key relationship between diet, GM, and health. 10.1038/s41522-021-00256-x
    Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages. Krishnan Smitha,Ding Yufang,Saedi Nima,Choi Maria,Sridharan Gautham V,Sherr David H,Yarmush Martin L,Alaniz Robert C,Jayaraman Arul,Lee Kyongbum Cell reports The gut microbiota plays a significant role in the progression of fatty liver disease; however, the mediators and their mechanisms remain to be elucidated. Comparing metabolite profile differences between germ-free and conventionally raised mice against differences between mice fed a low- and high-fat diet (HFD), we identified tryptamine and indole-3-acetate (I3A) as metabolites that depend on the microbiota and are depleted under a HFD. Both metabolites reduced fatty-acid- and LPS-stimulated production of pro-inflammatory cytokines in macrophages and inhibited the migration of cells toward a chemokine, with I3A exhibiting greater potency. In hepatocytes, I3A attenuated inflammatory responses under lipid loading and reduced the expression of fatty acid synthase and sterol regulatory element-binding protein-1c. These effects were abrogated in the presence of an aryl-hydrocarbon receptor (AhR) antagonist, indicating that the effects are AhR dependent. Our results suggest that gut microbiota could influence inflammatory responses in the liver through metabolites engaging host receptors. 10.1016/j.celrep.2018.03.109
    Effects of gut microbiota and fatty acid metabolism on dyslipidemia following weight-loss diets in women: Results from a randomized controlled trial. Ma Yiwei,Sun Yidi,Sun Liang,Liu Xin,Zeng Rong,Lin Xu,Li Yixue Clinical nutrition (Edinburgh, Scotland) BACKGROUND & AIMS:In our early feeding trial among overweight and obese Chinese women, both low-carbohydrate (LC) and calorie-restricted (CR) diets reduced weight and fat mass, but only the LC diet significantly improved dyslipidemia. We aimed to investigate the impacts of altered gut microbiota, fatty acid (FAs), and acylcarnitines, markers of mitochondrial function on blood lipids. METHODS:Fecal and blood samples from 48 participants at baseline and the end of a 12-week trial were used to perform metagenomics and targeted-metabolomics including erythrocyte FAs and plasma acylcarnitines, respectively. RESULTS:The two diets altered microbial structure and co-abundance gene clusters (CAGs) at different magnitudes. After a 12-week intervention, the Bacteroidetes/Firmicutes ratio increased significantly in the LC diet (P = 0.015) but not in the CR diet, which only showed an increased trend (P = 0.28). At the microbial function level, the LC group showed lower branched-chain amino acid biosynthesis and higher serine biosynthesis than the CR group. Moreover, the LC diet reduced levels of 14:0 and 16:1n-7 FAs in the de novo lipogenesis pathway, but increased 20:5n-3 compared with the CR diet. Both groups had increased plasma acylcarnitines except that the LC group had larger elevated short-chain acylcarnitines. After backward stepwise selection, a cluster of changed CAGs, FAs and acylcarnitines were found to be associated with improved lipid profile. However, changed CAGs showed higher contribution rates in elevating HDL-cholesterol (81.6%) and reducing triglycerides (89.3%) than changed FAs and acylcarnitines. CONCLUSIONS:The two weight-loss diets induced different changes of gut microbiota, plasma acylcarnitines, and erythrocyte FAs. Changes in gut microbiota rather than FA or acylcarnitine profiles showed greater contribution to improved lipid profile in these overweight and obese Chinese women. TRIAL REGISTRATION:The trial was registered at http://clinicaltrials.gov/show/NCT01358890. 10.1016/j.clnu.2021.09.021
    Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk. Li Jia V,Ashrafian Hutan,Bueter Marco,Kinross James,Sands Caroline,le Roux Carel W,Bloom Stephen R,Darzi Ara,Athanasiou Thanos,Marchesi Julian R,Nicholson Jeremy K,Holmes Elaine Gut BACKGROUND AND AIMS:Bariatric surgery is increasingly performed worldwide to treat morbid obesity and is also known as metabolic surgery to reflect its beneficial metabolic effects especially with respect to improvement in type 2 diabetes. Understanding surgical weight loss mechanisms and metabolic modulation is required to enhance patient benefits and operative outcomes. METHODS:The authors applied a parallel and statistically integrated bacterial profiling and metabonomic approach to characterise Roux-en-Y gastric bypass (RYGB) effects in a non-obese rat model. RESULTS:Substantial shifts of the main gut phyla towards higher concentrations of Proteobacteria (52-fold), specifically Enterobacter hormaechei, are shown. Low concentrations of Firmicutes (4.5-fold) and Bacteroidetes (twofold) in comparison with sham-operated rats were also found. Faecal extraction studies revealed a decrease in faecal bile acids and a shift from protein degradation to putrefaction through decreased faecal tyrosine with concomitant increases in faecal putrescine and diaminoethane. Decreased urinary amines and cresols were found and indices of modulated energy metabolism were demonstrated after RYGB, including decreased urinary succinate, 2-oxoglutarate, citrate and fumarate. These changes could also indicate renal tubular acidosis, which is associated with increased flux of mitochondrial tricarboxylic acid cycle intermediates. A surgically induced effect on the gut-brain-liver metabolic axis is inferred from modulated faecal γ-aminobutyric acid and glutamate. CONCLUSION:This profound co-dependence of mammalian and microbial metabolism, which is systematically altered after RYGB surgery, suggests that RYGB exerts local and global metabolic effects. The effect of RYGB surgery on the host metabolic-microbial cross-talk augments our understanding of the metabolic phenotype of bariatric procedures and can facilitate enhanced treatments for obesity-related diseases. 10.1136/gut.2010.234708
    Impact of Exercise on Gut Microbiota in Obesity. Aragón-Vela Jerónimo,Solis-Urra Patricio,Ruiz-Ojeda Francisco Javier,Álvarez-Mercado Ana Isabel,Olivares-Arancibia Jorge,Plaza-Diaz Julio Nutrients Physical activity, exercise, or physical fitness are being studied as helpful nonpharmacological therapies to reduce signaling pathways related to inflammation. Studies describing changes in intestinal microbiota have stated that physical activity could increase the microbial variance and enhance the ratio of Firmicutes/Bacteroidetes, and both actions could neutralize the obesity progression and diminish body weight. The aim of this review is to provide an overview of the literature describing the relationship between physical activity profiles and gut microbiota and in obesity and some associated comorbidities. Promoting physical activity could support as a treatment to maintain the gut microbiota composition or to restore the balance toward an improvement of dysbiosis in obesity; however, these mechanisms need to be studied in more detail. The opportunity to control the microbiota by physical activity to improve health results and decrease obesity and related comorbidities is very attractive. Nevertheless, several incompletely answered questions need to be addressed before this strategy can be implemented. 10.3390/nu13113999
    Obesity Modulates the Gut Microbiome in Triple-Negative Breast Cancer. Hossain Fokhrul,Majumder Samarpan,David Justin,Bunnell Bruce A,Miele Lucio Nutrients Triple-negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous subtype of breast cancer. Obesity is associated with increased incidence and worse prognosis in TNBC through various potential mechanisms. Recent evidence suggests that the gut microbiome plays a central role in the progression of cancer, and that imbalances or dysbiosis in the population of commensal microbiota can lead to inflammation and contribute to tumor progression. Obesity is characterized by low-grade inflammation, and gut dysbiosis is associated with obesity, chronic inflammation, and failure of cancer immunotherapy. However, the debate on what constitutes a "healthy" gut microbiome is ongoing, and the connection among the gut microbiome, obesity, and TNBC has not yet been addressed. This study aims to characterize the role of obesity in modulating the gut microbiome in a syngeneic mouse model of TNBC. 16S rRNA sequencing and metagenomic analyses were performed to analyze and annotate genus and taxonomic profiles. Our results suggest that obesity decreases alpha diversity in the gut microbiome. Metagenomic analysis revealed that obesity was the only significant factor explaining the similarity of the bacterial communities according to their taxonomic profiles. In contrast to the analysis of taxonomic profiles, the analysis of variation of functional profiles suggested that obesity status, tumor presence, and the obesity-tumor interaction were significant in explaining the variation of profiles, with obesity having the strongest correlation. The presence of tumor modified the profiles to a greater extent in obese than in lean animals. Further research is warranted to understand the impact of the gut microbiome on TNBC progression and immunotherapy. 10.3390/nu13103656
    Type 3 resistant starch from modulates obesity and obesity-related low-grade systemic inflammation in mice by regulating gut microbiota composition and metabolism. Wu Jiahui,Qiu Minyi,Zhang Chi,Zhang Caijuan,Wang Nan,Zhao Fangyuan,Lv Liqiao,Li Junling,Lyu-Bu A G A,Wang Ting,Zhao Baosheng,You Shaowei,Wu Yuanhua,Wang Xueyong Food & function Obesity is a most prevalent human health problem. Several studies showed that appropriate modulation of gut microbiota could help reshape the metabolic profile of obese individuals, thereby altering the development of obesity. A nutritional strategy for treating obesity includes prebiotics. Type 3 Resistant Starch from (Ce-RS3) is a dietary fiber that exerts potential effects on the intestinal microbial community; however, the metabolic landscape and anti-obesity mechanism remain unclear. In the present study, obese mice were treated with Ce-RS3, and 16S rRNA gene sequencing and metabolomics were used to measure changes in gut microbiota and fecal metabolic profiles, respectively. At the end of the treatment (13 weeks), we observed slow weight gain in the mice, and pathological damage and inflammation were substantially reduced. Ce-RS3 constructs a healthy gut microbiota structure and can enhance intestinal immunity and reduce metabolic inflammation. Ce-RS3 increased the diversity of gut microbiota with enrichment of and . Ce-RS3 regulated the systemic metabolic dysbiosis in obese mice and adjusted 26 abnormal metabolites in amino acids and lipids metabolism, many of which are related to the microbiome. More importantly, we found that the anti-obesity effect of Ce-RS3 can be transferred by fecal transplantation. The beneficial effects of Ce-RS3 might derive from gut microbiota changes, which might improve obesity and metabolic inflammation by altering host-microbiota interactions with impacts on the metabolome. In conclusion, Ce-RS3 can be used as a prebiotic with potential value for the treatment of obesity. 10.1039/d1fo02208c
    Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children. Zhang Chenhong,Yin Aihua,Li Hongde,Wang Ruirui,Wu Guojun,Shen Jian,Zhang Menghui,Wang Linghua,Hou Yaping,Ouyang Haimei,Zhang Yan,Zheng Yinan,Wang Jicheng,Lv Xiaofei,Wang Yulan,Zhang Feng,Zeng Benhua,Li Wenxia,Yan Feiyan,Zhao Yufeng,Pang Xiaoyan,Zhang Xiaojun,Fu Huaqing,Chen Feng,Zhao Naisi,Hamaker Bruce R,Bridgewater Laura C,Weinkove David,Clement Karine,Dore Joel,Holmes Elaine,Xiao Huasheng,Zhao Guoping,Yang Shengli,Bork Peer,Nicholson Jeremy K,Wei Hong,Tang Huiru,Zhang Xiaozhuang,Zhao Liping EBioMedicine Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader-Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation. RESEARCH IN CONTEXT:Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader-Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces. 10.1016/j.ebiom.2015.07.007
    Single-species versus dual-species probiotic supplementation as an emerging therapeutic strategy for obesity. Karimi G,Jamaluddin R,Mohtarrudin N,Ahmad Z,Khazaai H,Parvaneh M Nutrition, metabolism, and cardiovascular diseases : NMCD BACKGROUND AND AIM:Recent studies have reported beneficial effects of specific probiotics on obesity. However, the difference in the anti-obesity effects of probiotics as single species and dual species is still uncertain. Therefore, we aimed to compare the efficacy of single and dual species of bacteria on markers of obesity in high-fat diet-induced obese rats. METHODS AND RESULTS:A total of 40 male Sprague-Dawley rats were assigned to one of five groups of varying diets as follows: standard diet, high fat diet (HFD), HFD supplemented with Lactobacillus casei strain Shirota, HFD supplemented with Bifidobacterium longum and HFD supplemented with a mixture of these two bacterial species. After 15 weeks of supplementation, the animals were examined for changes in body weight, body fat, total count of bacteria in fecal, blood serum lipid profile, leptin, adiponectin and inflammatory biomarkers. Histological analysis of the liver and adipose tissue was performed and the hepatic mRNA expression levels of genes related to lipid metabolism were measured. It was found that probiotic supplementation of either B. longum or a mixture of B. longum and LcS bacteria significantly reduced weight and triglycerides in the HFD groups. Supplementation of B. longum bacteria showed better results in terms of modulating leptin level, fat mass, adipocyte size and lipoprotein lipase expression, as well as increasing adiponectin and peroxisome proliferator-activated receptors-γ expression compared to dual species of bacteria. No significant differences were observed in the total count of fecal bacteria, glucose and inflammatory biomarker levels between supplemented groups. CONCLUSIONS:B. longum supplementation in obesity was more beneficial in metabolic profile changes than the mixture species. 10.1016/j.numecd.2017.06.020
    Antibiotic-induced Disruption of Intestinal Microbiota Contributes to Failure of Vertical Sleeve Gastrectomy. Jahansouz Cyrus,Staley Christopher,Kizy Scott,Xu Hongliang,Hertzel Ann V,Coryell Jessi,Singroy Stephanie,Hamilton Matthew,DuRand Meri,Bernlohr David A,Sadowsky Michael J,Khoruts Alexander,Ikramuddin Sayeed Annals of surgery OBJECTIVE:The aim of this study was to test whether the perioperative composition of intestinal microbiota can contribute to variable outcomes following vertical sleeve gastrectomy (VSG). SUMMARY OF BACKGROUND DATA:Although bariatric surgery is the most effective treatment for obesity, metabolic outcomes are variable. METHODS:Diet-induced obese mice were randomized to VSG or sham surgery, with or without exposure to antibiotics that selectively suppress mainly gram-positive (fidaxomicin, streptomycin) or gram-negative (ceftriaxone) bacteria on postoperative days (POD) 1-4. Fecal microbiota was characterized before surgery and on POD 7 and 28. Mice were metabolically characterized on POD 30-32 and euthanized on POD 35. RESULTS:VSG resulted in weight loss and shifts in the intestinal microbiota composition relative to sham-operated mice. Antibiotic exposure resulted in sustained reductions in alpha (within-sample) diversity of microbiota and shifts in its composition. All antibiotic treatments proved to be detrimental to metabolic VSG outcomes, regardless of antimicrobial specificity of antibiotics. These effects involved functionally distinct pathways. Specifically, fidaxomicin and streptomycin markedly altered hepatic bile acid signaling and lipid metabolism, while ceftriaxone resulted in greater reduction of key antimicrobial peptides. However, VSG mice exposed to antibiotics, regardless of their specificity, had significantly increased subcutaneous adiposity and impaired glucose homeostasis without changes in food intake relative to control VSG mice. CONCLUSION:Dysbiosis induced by brief perioperative antibiotic exposure attenuates weight loss and metabolic improvement following VSG. Potential mechanisms include disruption of bile acid homeostasis and reduction in the production of gut antimicrobial peptides. Results of this study implicate the intestinal microbiota as an important contributor to metabolic homeostasis and a potentially modifiable target influencing clinical outcomes following VSG. 10.1097/SLA.0000000000002729
    Effects of the Dietary Protein and Carbohydrate Ratio on Gut Microbiomes in Dogs of Different Body Conditions. Li Qinghong,Lauber Christian L,Czarnecki-Maulden Gail,Pan Yuanlong,Hannah Steven S mBio Obesity has become a health epidemic in both humans and pets. A dysbiotic gut microbiota has been associated with obesity and other metabolic disorders. High-protein, low-carbohydrate (HPLC) diets have been recommended for body weight loss, but little is known about their effects on the canine gut microbiome. Sixty-three obese and lean Labrador retrievers and Beagles (mean age, 5.72 years) were fed a common baseline diet for 4 weeks in phase 1, followed by 4 weeks of a treatment diet, specifically, the HPLC diet (49.4% protein, 10.9% carbohydrate) or a low-protein, high-carbohydrate (LPHC) diet (25.5% protein, 38.8% carbohydrate) in phase 2. 16S rRNA gene profiling revealed that dietary protein and carbohydrate ratios have significant impacts on gut microbial compositions. This effect appeared to be more evident in obese dogs than in lean dogs but was independent of breed. Consumption of either diet increased the bacterial evenness, but not the richness, of the gut compared to that after consumption of the baseline diet. Macronutrient composition affected taxon abundances, mainly within the predominant phyla, Firmicutes and Bacteroidetes The LPHC diet appeared to favor the growth of Bacteroides uniformis and Clostridium butyricum, while the HPLC diet increased the abundances of Clostridium hiranonis, Clostridium perfringens, and Ruminococcus gnavus and enriched microbial gene networks associated with weight maintenance. In addition, we observed a decrease in the Bacteroidetes to Firmicutes ratio and an increase in the Bacteroides to Prevotella ratio in the HPLC diet-fed dogs compared to these ratios in dogs fed other diets. Finally, analysis of the effect of diet on the predicted microbial gene network was performed using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). IMPORTANCE:More than 50% of dogs are either overweight or obese in the United States. A dysbiotic gut microbiota is associated with obesity and other metabolic problems in humans. HPLC diets have been promoted as an effective weight loss strategy for many years, and potential effects were reported for both humans and dogs. In this study, we explored the influence of the protein and carbohydrate ratio on the gut microbiome in dogs with different body conditions. We demonstrated significant dietary effects on the gut microbiome, with greater changes in obese dogs than in lean dogs. The HPLC diet-fed dogs showed greater abundances of Firmicutes but fewer numbers of Bacteroidetes than other dogs. This knowledge will enable us to use prebiotics, probiotics, and other nutritional interventions to modulate the gut microbiota and to provide an alternative therapy for canine obesity. 10.1128/mBio.01703-16
    Comparison of Diet versus Exercise on Metabolic Function and Gut Microbiota in Obese Rats. Welly Rebecca J,Liu Tzu-Wen,Zidon Terese M,Rowles Joe L,Park Young-Min,Smith T Nicholas,Swanson Kelly S,Padilla Jaume,Vieira-Potter Victoria J Medicine and science in sports and exercise UNLABELLED:Cardiometabolic impairments that begin early in life are particularly critical, because they often predict metabolic dysfunction in adulthood. Obesity, high-fat diet (HFD), and inactivity are all associated with adipose tissue (AT) inflammation and insulin resistance (IR), major predictors of metabolic dysfunction. Recent evidence has also associated the gut microbiome with cardiometabolic health. PURPOSE:The objective of this study is to compare equal energy deficits induced by exercise and caloric reduction on cardiometabolic disease risk parameters including AT inflammation, IR, and gut microbiota changes during HFD consumption. METHODS:Obesity-prone rats fed HFD were exercise trained (Ex, n = 10) or weight matched to Ex via caloric reduction although kept sedentary (WM, n = 10), and compared with ad libitum HFD-fed (Sed, n = 10) rats for IR, systemic energetics and spontaneous physical activity (SPA), adiposity, and fasting metabolic parameters. Visceral, subcutaneous, periaortic, and brown AT (BAT), liver, aorta, and cecal digesta were examined. RESULTS:Despite identical reductions in adiposity, Ex, but not WM, improved IR, increased SPA by approximately 26% (P < 0.05 compared with WM and Sed), and reduced LDL cholesterol (P < 0.05 compared with Sed). WM and Ex both reduced inflammatory markers in all AT depots and aorta, whereas only Ex increased indicators of mitochondrial function in BAT. Ex significantly increased the relative abundance of cecal Streptococcaceae and decreased S24-7 and one undefined genus in Rikenellaceae; WM induced similar changes but did not reach statistical significance. CONCLUSIONS:Both Ex and WM reduced AT inflammation across depots, whereas Ex caused more robust changes to gut microbial communities, improved IR, increased fat oxidation, increased SPA, and increased indices of BAT mitochondrial function. Our findings add to the growing body of literature indicating that there are weight-loss-independent metabolic benefits of exercise. 10.1249/MSS.0000000000000964
    Roux-Y Gastric Bypass and Sleeve Gastrectomy directly change gut microbiota composition independent of surgery type. Paganelli Fernanda L,Luyer Misha,Hazelbag C Marijn,Uh Hae-Won,Rogers Malbert R C,Adriaans Danielle,Berbers Roos-Marijn,Hendrickx Antoni P A,Viveen Marco C,Groot James A,Bonten Marc J M,Fluit Ad C,Willems Rob J L,Leavis Helen L Scientific reports Bariatric surgery in morbid obesity, either through sleeve gastrectomy (SG) or Roux-Y gastric bypass (RYGB), leads to sustainable weight loss, improvement of metabolic disorders and changes in intestinal microbiota. Yet, the relationship between changes in gut microbiota, weight loss and surgical procedure remains incompletely understood. We determined temporal changes in microbiota composition in 45 obese patients undergoing crash diet followed by SG (n = 22) or RYGB (n = 23). Intestinal microbiota composition was determined before intervention (baseline, S1), 2 weeks after crash diet (S2), and 1 week (S3), 3 months (S4) and 6 months (S5) after surgery. Relative to S1, the microbial diversity index declined at S2 and S3 (p < 0.05), and gradually returned to baseline levels at S5. Rikenellaceae relative abundance increased and Ruminococcaceae and Streptococcaceae abundance decreased at S2 (p < 0.05). At S3, Bifidobacteriaceae abundance decreased, whereas those of Streptococcaceae and Enterobacteriaceae increased (p < 0.05). Increased weight loss between S3-S5 was not associated with major changes in microbiota composition. No significant differences appeared between both surgical procedures. In conclusion, undergoing a crash diet and bariatric surgery were associated with an immediate but temporary decline in microbial diversity, with immediate and permanent changes in microbiota composition, independent of surgery type. 10.1038/s41598-019-47332-z
    Changes of gut microbiota between different weight reduction programs. Lin Belle Yanyu,Lin Wei-De,Huang Chih-Kun,Hsin Ming-Che,Lin Wen-Yuan,Pryor Aurora D Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery BACKGROUND:Gut microbiota may induce obesity, diabetes, and metabolic syndrome. Different weight reduction programs may induce different changes in gut microbiota. OBJECTIVES:To assess the changes in gut microbiota between obese adults who participated in 2 different weight reduction programs, the dietary counseling (DC) group and sleeve gastrectomy (SG) group, for 3 months. SETTING:A University Hospital. METHODS:Ten obese participants from each group were matched according to sex, age, and body mass index. Gut microbiota compositions were determined by metagenomics using next-generation sequencing before and after treatment. Anthropometric indices, metabolic factors, and gut microbiota were compared between and within groups. RESULTS:After 3 months of treatment, compared with subjects in DC group, subjects in SG group experienced a greater reduction in body weight, body mass index, body fat, waist and hip circumference, diastolic blood pressure, hemoglobin, insulin, insulin resistance, glutamate pyruvate transaminase, blood urine nitrogen, and glycated hemoglobin (HbA1C). A total of 8, 17, and 46 species experienced significant abundance changes in DC, in SG, and between the 2 groups, respectively. Diversity of the gut flora increased in SG and between the 2 groups after treatment. The weight change over the course of the weight loss program was further adjusted and only 4 species, including Peptoniphilus lacrimalis 315 B, Selenomonas 4 sp., Prevotella 2 sp., and Pseudobutyrivibrio sp., were found to be significantly different between the 2 weight loss programs. These 4 species may be the different gut microbiota change between internal and surgical weight reduction programs. CONCLUSIONS:There are significant differences not only in anthropometric indices and metabolic factors but also in gut microbiota change between the 2 programs. 10.1016/j.soard.2019.01.026
    Link between gut microbiota and health outcomes in inulin -treated obese patients: Lessons from the Food4Gut multicenter randomized placebo-controlled trial. Hiel Sophie,Gianfrancesco Marco A,Rodriguez Julie,Portheault Daphnée,Leyrolle Quentin,Bindels Laure B,Gomes da Silveira Cauduro Carolina,Mulders Maria D G H,Zamariola Giorgia,Azzi Anne-Sophie,Kalala Gaetan,Pachikian Barbara D,Amadieu Camille,Neyrinck Audrey M,Loumaye Audrey,Cani Patrice D,Lanthier Nicolas,Trefois Pierre,Klein Olivier,Luminet Olivier,Bindelle Jérôme,Paquot Nicolas,Cnop Miriam,Thissen Jean-Paul,Delzenne Nathalie M Clinical nutrition (Edinburgh, Scotland) BACKGROUND:The gut microbiota is altered in obesity and is strongly influenced by nutrients and xenobiotics. We have tested the impact of native inulin as prebiotic present in vegetables and added as a supplement on gut microbiota-related outcomes in obese patients. Metformin treatment was analyzed as a potential modulator of the response. METHODS:A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in 150 obese patients who received 16 g/d native inulin versus maltodextrin, coupled to dietary advice to consume inulin-rich versus -poor vegetables for 3 months, respectively, in addition to dietary caloric restriction. Anthropometry, diagnostic imaging (abdominal CT-scan, fibroscan), food-behavior questionnaires, serum biology and fecal microbiome (primary outcome; 16S rDNA sequencing) were analyzed before and after the intervention. RESULTS:Both placebo and prebiotic interventions lowered energy intake, BMI, systolic blood pressure, and serum γ-GT. The prebiotic induced greater weight loss and additionally decreased diastolic blood pressure, AST and insulinemia. Metformin treatment compromised most of the gut microbiota changes and metabolic improvements linked to prebiotic intervention. The prebiotic modulated specific bacteria, associated with the improvement of anthropometry (i.e. a decrease in Desulfovibrio and Clostridium sensu stricto). A large increase in Bifidobacterium appears as a signature of inulin intake rather than a driver of prebiotic-linked biological outcomes. CONCLUSIONS:Inulin-enriched diet is able to promote weight loss in obese patients, the treatment efficiency being related to gut microbiota characteristics. This treatment is more efficacious in patients who did not receive metformin as anti-diabetic drugs prior the intervention, supporting that both drug treatment and microbiota might be taken into account in personalized nutrition interventions. Registered under ClinicalTrials.gov Identifier no NCT03852069. 10.1016/j.clnu.2020.04.005
    Sleeve gastrectomy drives persistent shifts in the gut microbiome. Jahansouz Cyrus,Staley Christopher,Bernlohr David A,Sadowsky Michael J,Khoruts Alexander,Ikramuddin Sayeed Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery BACKGROUND:Changes in the gut microbiome following bariatric surgery have been causally linked to metabolic benefits. OBJECTIVES:We sought to characterize and assess the stability of gut microbiome shifts following sleeve gastrectomy (SG). SETTING:University laboratories. METHODS:Diet-induced obese mice were randomized to SG or sham surgery. Mice were housed individually or cohoused such that one SG mouse was housed with one weight-matched, sham-operated mouse. Fecal samples were collected before and on postoperative days 7 and 28. Bacterial composition in feces was characterized by using next-generation Illumina sequencing of 16 S rRNA. RESULTS:SG mice lost more weight and were more insulin sensitive than sham mice independent of housing status (P<.05). One week following surgery, fecal samples from all mice showed shifts in the microbiome that only persisted in SG-operated mice. Cohousing did not alter the microbial composition of SG-operated mice. Cohoused sham-operated mice showed a unique shift in microbial composition on postoperative day 28 that differed from individually housed, sham-operated mice (P<.001). Cohousing did not affect metabolic outcomes of either SG or sham surgeries. CONCLUSION:SG results in acute and sustained shifts in the gut microbiome. SG associated shifts are not altered by reexposure to obesity-associated gut microbiota. 10.1016/j.soard.2017.01.003
    Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Dao Maria Carlota,Everard Amandine,Aron-Wisnewsky Judith,Sokolovska Nataliya,Prifti Edi,Verger Eric O,Kayser Brandon D,Levenez Florence,Chilloux Julien,Hoyles Lesley, ,Dumas Marc-Emmanuel,Rizkalla Salwa W,Doré Joel,Cani Patrice D,Clément Karine Gut OBJECTIVE:Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with body fat mass and glucose intolerance in mice, but more evidence is needed in humans. The impact of diet and weight loss on this bacterial species is unknown. Our objective was to evaluate the association between faecal A. muciniphila abundance, faecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR). DESIGN:The intervention consisted of a 6-week CR period followed by a 6-week weight stabilisation diet in overweight and obese adults (N=49, including 41 women). Faecal A. muciniphila abundance, faecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and weight stabilisation. RESULTS:At baseline A. muciniphila was inversely related to fasting glucose, waist-to-hip ratio and subcutaneous adipocyte diameter. Subjects with higher gene richness and A. muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution. Individuals with higher baseline A. muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR. These participants also experienced a reduction in A. muciniphila abundance, but it remained significantly higher than in individuals with lower baseline abundance. A. muciniphila was associated with microbial species known to be related to health. CONCLUSIONS:A. muciniphila is associated with a healthier metabolic status and better clinical outcomes after CR in overweight/obese adults. The interaction between gut microbiota ecology and A. muciniphila warrants further investigation. TRIAL REGISTRATION NUMBER:NCT01314690. 10.1136/gutjnl-2014-308778
    Effect on gut microbiota of a 1-y lifestyle intervention with Mediterranean diet compared with energy-reduced Mediterranean diet and physical activity promotion: PREDIMED-Plus Study. Muralidharan Jananee,Moreno-Indias Isabel,Bulló Mónica,Lopez Jesús Vioque,Corella Dolores,Castañer Olga,Vidal Josep,Atzeni Alessandro,Fernandez-García Jose Carlos,Torres-Collado Laura,Fernández-Carrión Rebeca,Fito Monsterrat,Olbeyra Romina,Gomez-Perez Ana Maria,Galiè Serena,Bernal-López Maria Rosa,Martinez-Gonzalez Miguel Angel,Salas-Salvadó Jordi,Tinahones Francisco Jose The American journal of clinical nutrition BACKGROUND:The Mediterranean diet is a well-recognized healthy diet that has shown to induce positive changes in gut microbiota. Lifestyle changes such as diet along with physical activity could aid in weight loss and improve cardiovascular risk factors. OBJECTIVES:To investigate the effect of an intensive lifestyle weight loss intervention on gut microbiota. METHODS:This is a substudy of the PREDIMED-Plus (Prevención con Dieta Mediterránea-Plus), a randomized controlled trial conducted in overweight/obese men and women (aged 55-75 y) with metabolic syndrome. The intervention group (IG) underwent an intensive weight loss lifestyle intervention based on an energy-restricted Mediterranean diet (MedDiet) and physical activity promotion, and the control group (CG) underwent a non-energy-restricted MedDiet for 1 y. Anthropometric, biochemical, and gut microbial 16S rRNA sequencing data were analyzed at baseline (n = 362) and 1-y follow-up (n = 343). RESULTS:IG participants had a weight loss of 4.2 (IQR, -6.8, -2.5) kg compared with 0.2 (IQR, -2.1, 1.4) kg in the CG (P < 0.001). Reductions in BMI, fasting glucose, glycated hemoglobin, and triglycerides and an increase in HDL cholesterol were greater in IG than in CG participants (P < 0.05). We observed a decrease in Butyricicoccus, Haemophilus, Ruminiclostridium 5, and Eubacterium hallii in the IG compared with the CG. Many genera shifted in the same direction within both intervention groups, indicating an overall effect of the MedDiet. Decreases in Haemophilus, Coprococcus 3, and few other genera were associated with a decrease in adiposity parameters in both intervention groups. Changes in Lachnospiraceae NK4A136 were positively associated with changes in MedDiet adherence. CONCLUSIONS:Weight loss induced by an energy-restricted MedDiet and physical activity induce changes in gut microbiota. The role of MedDiet-induced changes on the host might be via short-chain fatty acid producing bacteria, whereas with energy restriction, these changes might be modulated with other mechanisms, which need to be explored in future studies. This trial was registered at http://www.isrctn.com/ISRCTN89898870 as ISRCT 89898870. 10.1093/ajcn/nqab150
    Circulating Gut Microbiota Metabolite Trimethylamine N-Oxide (TMAO) and Changes in Bone Density in Response to Weight Loss Diets: The POUNDS Lost Trial. Zhou Tao,Heianza Yoriko,Chen Yuhang,Li Xiang,Sun Dianjianyi,DiDonato Joseph A,Pei Xiaofang,LeBoff Meryl S,Bray George A,Sacks Frank M,Qi Lu Diabetes care OBJECTIVE:Type 2 diabetes is related to obesity and altered bone health, and both are affected by gut microbiota. We examined associations of weight loss diet-induced changes in a gut microbiota-related metabolite trimethylamine N-oxide (TMAO), and its precursors (choline and l-carnitine), with changes in bone mineral density (BMD) considering diabetes-related factors. RESEARCH DESIGN AND METHODS:In the 2-year Preventing Overweight Using Novel Dietary Strategies trial (POUNDS Lost), 264 overweight and obese participants with measurement of BMD by DXA scan were included in the present analysis. The participants were randomly assigned to one of four diets varying in macronutrient intake. Association analysis was performed in pooled participants and different diet groups. Changes in blood levels of TMAO, choline, and l-carnitine from baseline to 6 months after the dietary intervention were calculated. RESULTS:We found that a greater reduction in plasma levels of TMAO from baseline to 6 months was associated with a greater loss in whole-body BMD at 6 months and 2 years ( = 0.03 and = 0.02). The greater reduction in TMAO was also associated with a greater loss in spine BMD ( = 0.005) at 2 years, independent of body weight changes. The associations were not modified by baseline diabetes status and glycemic levels. Changes in l-carnitine, a precursor of TMAO, showed interactions with dietary fat intake in regard to changes of spine BMD and hip BMD at 6 months (all < 0.05). Participants with the smallest decrease in l-carnitine showed less bone loss in the low-fat diet group than the high-fat diet group ( = 0.03 and = 0.02). CONCLUSIONS:TMAO might protect against BMD reduction during weight loss, independent of diet interventions varying in macronutrient content and baseline diabetes risk factors. Dietary fat may modify the relation between change in plasma l-carnitine level and changes in BMD. Our findings highlight the importance of investigating the relation between TMAO and bone health in patients with diabetes. 10.2337/dc19-0134
    Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women. Alemán José O,Bokulich Nicholas A,Swann Jonathan R,Walker Jeanne M,De Rosa Joel Correa,Battaglia Thomas,Costabile Adele,Pechlivanis Alexandros,Liang Yupu,Breslow Jan L,Blaser Martin J,Holt Peter R Journal of translational medicine BACKGROUND:Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. METHODS:We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways. RESULTS:Alterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-α-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue. CONCLUSIONS:VLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome. Trial Registration ClinicalTrials.gov NCT01699906, 4-Oct-2012, Retrospectively registered. URL- https://clinicaltrials.gov/ct2/show/NCT01699906. 10.1186/s12967-018-1619-z
    Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial. Roager Henrik Munch,Vogt Josef K,Kristensen Mette,Hansen Lea Benedicte S,Ibrügger Sabine,Mærkedahl Rasmus B,Bahl Martin Iain,Lind Mads Vendelbo,Nielsen Rikke L,Frøkiær Hanne,Gøbel Rikke Juul,Landberg Rikard,Ross Alastair B,Brix Susanne,Holck Jesper,Meyer Anne S,Sparholt Morten H,Christensen Anders F,Carvalho Vera,Hartmann Bolette,Holst Jens Juul,Rumessen Jüri Johannes,Linneberg Allan,Sicheritz-Pontén Thomas,Dalgaard Marlene D,Blennow Andreas,Frandsen Henrik Lauritz,Villas-Bôas Silas,Kristiansen Karsten,Vestergaard Henrik,Hansen Torben,Ekstrøm Claus T,Ritz Christian,Nielsen Henrik Bjørn,Pedersen Oluf Borbye,Gupta Ramneek,Lauritzen Lotte,Licht Tine Rask Gut OBJECTIVE:To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN:60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. RESULTS:50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. CONCLUSION:Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. TRIAL REGISTRATION NUMBER:NCT01731366; Results. 10.1136/gutjnl-2017-314786
    Diet- and sex-related changes of gut microbiota composition and functional profiles after 4 months of weight loss intervention. European journal of nutrition PURPOSE:Obesity has been related to intestinal dysbiosis and the modification of gut microbiota composition by dietary strategies becomes a promising strategy to help manage obesity. The aim of the current study was to evaluate the effect of two weight-loss diets on the composition and functional profile of gut microbiota. METHODS:55 men and 124 women with BMI > 25 kg/m were randomly assigned to moderately high-protein (MHP) or low-fat (LF) diet. Differences in fecal bacteria abundance (based on 16 s rRNA sequencing) between before and after 4 months of calorie restriction was analyzed using EdgeR tool in MicrobiomeAnalyst platform. Bacterial functional profile was predicted using Tax4Fun and metagenomeSeq analysis. Significant KEGG Orthology (KO) terms were selected for the metabolomic study using chromatography. RESULTS:After the intervention, MHP-men showed a significant decrease in Negativicutes, Selenomonadales, Dielma and Dielma fastidiosa. LF-men showed a significant increase in Bacilli, Lactobacillales, Christensenellaceae, Peptococcaceae, and Streptococcaceae, Peptococcus, Streptococcus and Christensenella, Duncaniella dubosii_CP039396_93.49%, Roseburia sp_AB744234_98.96% and Alistipes inops_KJ572413_99.57%. MHP-women increased Pasteurellales, Phascolarctobacterium succinatutens, Ruthenibacterium lactatiformans_LR215981_99.55% and decreased in Phascolarctobacterium succinatutens_NR112902_99.56%. Finally, LF-women presented a significant decrease in Bacteroides clarus and Erysipelothrix inopinata_CP060715_84.4%. Surprisingly, no matching bacterial changes were found between these four groups. A total of 42 KO, 10 metabolic pathways and 107 related metabolites related were found implicated in these bacterial changes. Seven metabolites were confirmed in plasma. CONCLUSION:Weight-loss-related-changes in gut microbiome composition and the functional profile occur in a sex- and diet-related manner, showing that women and men could differentially benefit from the consumption of MHP and LF diets. TRIAL REGISTRATION:NCT02737267, 10th March 2016 retrospectively registered. 10.1007/s00394-021-02508-0
    Associations of plasma trimethylamine N-oxide, choline, carnitine, and betaine with inflammatory and cardiometabolic risk biomarkers and the fecal microbiome in the Multiethnic Cohort Adiposity Phenotype Study. Fu Benjamin C,Hullar Meredith A J,Randolph Timothy W,Franke Adrian A,Monroe Kristine R,Cheng Iona,Wilkens Lynne R,Shepherd John A,Madeleine Margaret M,Le Marchand Loïc,Lim Unhee,Lampe Johanna W The American journal of clinical nutrition BACKGROUND:Trimethylamine N-oxide (TMAO), a compound derived from diet and metabolism by the gut microbiome, has been associated with several chronic diseases, although the mechanisms of action are not well understood and few human studies have investigated microbes involved in its production. OBJECTIVES:Our study aims were 1) to investigate associations of TMAO and its precursors (choline, carnitine, and betaine) with inflammatory and cardiometabolic risk biomarkers; and 2) to identify fecal microbiome profiles associated with TMAO. METHODS:We conducted a cross-sectional analysis using data collected from 1653 participants (826 men and 827 women, aged 60-77 y) in the Multiethnic Cohort Study. Plasma concentrations of TMAO and its precursors were measured by LC-tandem MS. We also analyzed fasting blood for markers of inflammation, glucose and insulin, cholesterol, and triglycerides (TGs), and further measured blood pressure. Fecal microbiome composition was evaluated by sequencing the 16S ribosomal RNA gene V1-V3 region. Associations of TMAO and its precursors with disease risk biomarkers were assessed by multivariable linear regression, whereas associations between TMAO and the fecal microbiome were assessed by permutational multivariate ANOVA and hurdle regression models using the negative binomial distribution. RESULTS:Median (IQR) concentration of plasma TMAO was 3.05 μmol/L (2.10-4.60 μmol/L). Higher concentrations of TMAO and carnitine, and lower concentrations of betaine, were associated with greater insulin resistance (all P < 0.02). Choline was associated with higher systolic blood pressure, TGs, lipopolysaccharide-binding protein, and lower HDL cholesterol (P ranging from <0.001 to 0.03), reflecting an adverse cardiometabolic risk profile. TMAO was associated with abundance of 13 genera (false discovery rate < 0.05), including Prevotella, Mitsuokella, Fusobacterium, Desulfovibrio, and bacteria belonging to the families Ruminococcaceae and Lachnospiraceae, as well as the methanogen Methanobrevibacter smithii. CONCLUSIONS:Plasma TMAO concentrations were associated with a number of trimethylamine-producing bacterial taxa, and, along with its precursors, may contribute to inflammatory and cardiometabolic risk pathways. 10.1093/ajcn/nqaa015
    Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) potentially increases the risk of obesity in adults: An exploratory systematic review and dose-response meta- analysis. Dehghan Parvin,Farhangi Mahdieh Abbasalizad,Nikniaz Leila,Nikniaz Zeinab,Asghari-Jafarabadi Mohammad Obesity reviews : an official journal of the International Association for the Study of Obesity It has been suggested that trimethylamine N-oxide (TMAO) is associated with increased risk of diabetes and cardiovascular disease (CVD) morbidity and mortality. However, it is not known whether increased TMAO concentrations is associated with obesity. In the current study, we summarized the evidence related to the association of circulating TMAO with the risk of obesity measurements, including body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) in a two-class and dose-response meta-analysis of observational studies. A systematic search carried out in PubMed, SCOPUS, Cochrane, and ProQuest through September 30, 2019 resulted in 12 eligible studies which were included in the current meta-synthesis. In these studies, BMI was reported but there were no reports of WC or WHR. Meta-analysis of two-class variables and dose-response meta-analysis of continuous variables were performed. Subgroup analysis and meta-regression were also performed to identify the source of heterogeneity. There was a dose-response association between circulating TMAO concentration and increased BMI in studies involving healthy individuals (P nonlinearity = .007), while no evidence of departure from linearity was observed according to study design or among patients with CVD. Results showed the highest category of TMAO was associated with 0.56 kg/m increase in BMI (weighted mean difference [WMD], 0.563; CI, 0.026-1.100; P = .04). The results of the current meta-analysis revealed a positive association between circulating TMAO and obesity as presented by increased BMI. Moreover, a dose-dependent association between circulating TMAO and obesity was also identified in apparently healthy individuals. This is the first meta-analysis to reveal positive dose-dependent associations between circulating TMAO concentration and obesity. 10.1111/obr.12993
    Weight-loss interventions and gut microbiota changes in overweight and obese patients: a systematic review. Seganfredo F B,Blume C A,Moehlecke M,Giongo A,Casagrande D S,Spolidoro J V N,Padoin A V,Schaan B D,Mottin C C Obesity reviews : an official journal of the International Association for the Study of Obesity Imbalances in the gut microbiota, the bacteria that inhabit the intestines, are central to the pathogenesis of obesity. This systematic review assesses the association between the gut microbiota and weight loss in overweight/obese adults and its potential manipulation as a target for treating obesity. This review identified 43 studies using the keywords 'overweight' or 'obesity' and 'microbiota' and related terms; among these studies, 17 used dietary interventions, 11 used bariatric surgery and 15 used microbiota manipulation. The studies differed in their methodologies as well as their intervention lengths. Restrictive diets decreased the microbiota abundance, correlated with nutrient deficiency rather than weight loss and generally reduced the butyrate producers Firmicutes, Lactobacillus sp. and Bifidobacterium sp. The impact of surgical intervention depended on the given technique and showed a similar effect on butyrate producers, in addition to increasing the presence of the Proteobacteria phylum, which is related to changes in the intestinal absorptive surface, pH and digestion time. Probiotics differed in strain and duration with diverse effects on the microbiota, and they tended to reduce body fat. Prebiotics had a bifidogenic effect and increased butyrate producers, likely due to cross-feeding interactions, contributing to the gut barrier and improving metabolic outcomes. All of the interventions under consideration had impacts on the gut microbiota, although they did not always correlate with weight loss. These results show that restrictive diets and bariatric surgery reduce microbial abundance and promote changes in microbial composition that could have long-term detrimental effects on the colon. In contrast, prebiotics might restore a healthy microbiome and reduce body fat. 10.1111/obr.12541
    Kaempferol reduces obesity, prevents intestinal inflammation, and modulates gut microbiota in high-fat diet mice. Bian Yifei,Lei Jiaqi,Zhong Jia,Wang Bo,Wan Yan,Li Jinxin,Liao Chaoyong,He Yang,Liu Zhongjie,Ito Koichi,Zhang Bingkun The Journal of nutritional biochemistry Kaempferol, a flavonoid identified in a wide variety of dietary sources, has been reported to possess anti-obesity properties; however, its underlying mechanism was poorly understood. Chronic, low-grade gut inflammation and dysbacteria are proposed as underlying factors as well as novel treatment approaches for obesity-associated pathologies. This present study aims to investigate the benefits of experimental treatment with kaempferol on intestinal inflammation and gut microbial balance in animal model of obesity. High fat diet (HFD) was applied to C57BL/6J mice for 16 weeks, during which the supplement of kaempferol served as a variable. Clearly, HFD induced obesity, fat accumulation, glucose intolerance and adipose inflammation, the metabolic syndrome of which was the main finding. All these metabolic disorders can be alleviated through kaempferol supplementation. In addition, increased intestinal permeability, infiltration of immunocytes (macrophage, dendritic cells and neutrophils) and overexpression of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, monocyte chemoattractant protein-1) were also found in the HFD-induced mice. Kaempferol supplementation improved intestinal barrier integrity and inhibited gut inflammation, by reducing the activation of TLR4/NF-κB pathway. Furthermore, the characterization of the cecal microbiota by sequencing showed that kaempferol supplementation was able to counteract the dysbiosis associated to obesity. Our study delineated the multiple mechanism of action underlying the anti-obesity effect of kaempferol, and provide scientific evidence to support the development of kaempferol as a dietary supplement for obesity treatment. 10.1016/j.jnutbio.2021.108840
    The role of in obesity, diabetes and atherosclerosis. Hasani Alka,Ebrahimzadeh Saba,Hemmati Fatemeh,Khabbaz Aytak,Hasani Akbar,Gholizadeh Pourya Journal of medical microbiology Alteration in the composition of the gut microbiota can lead to a number of chronic clinical diseases. is an anaerobic bacteria constituting 3-5% of the gut microbial community in healthy adults. This bacterium is responsible for degenerating mucin in the gut; its scarcity leads to diverse clinical disorders. In this review, we focus on the role of in diabetes, obesity and atherosclerosis, as well as the use of this bacterium as a next-generation probiotic. In regard to obesity and diabetes, human and animal trials have shown that controls the essential regulatory system of glucose and energy metabolism. However, the underlying mechanisms by which alleviates the complications of obesity, diabetes and atherosclerosis are unclear. At the same time, its abundance suggests improved metabolic disorders, such as metabolic endotoxemia, adiposity insulin resistance and glucose tolerance. The role of is implicated in declining aortic lesions and atherosclerosis. Well-characterized virulence factors, antigens and cell wall extracts of may act as effector molecules in these diseases. These molecules may provide novel mechanisms and strategies by which this bacterium could be used as a probiotic for the treatment of obesity, diabetes and atherosclerosis. 10.1099/jmm.0.001435
    The Potential Roles of Very Low Calorie, Very Low Calorie Ketogenic Diets and Very Low Carbohydrate Diets on the Gut Microbiota Composition. Rondanelli Mariangela,Gasparri Clara,Peroni Gabriella,Faliva Milena Anna,Naso Maurizio,Perna Simone,Bazire Philip,Sajuox Ignacio,Maugeri Roberto,Rigon Chiara Frontiers in endocrinology Several studies have described a strong correlation between diet, weight loss, and gut microbiota composition. The aim of this review was to evaluate the potential effects of energy-restricted diets, namely very low calorie diets (VLCDs), very low calorie ketogenic diets (VLCKDs), and very low carbohydrate diets (VLCarbDs), on the composition of the gut microbiota in humans. We performed a literature search using the following terms (with their abbreviations or acronyms): "very low calorie diet", "very low calorie ketogenic diet", "very low carbohydrate diet", and "gut microbiota". Our search strategy retrieved nine eligible studies. Overall, VLCDs and VLCarbDs affected the Bacteroidetes to Firmicutes ratio in obese patients, leading to a reduction in short-chain fatty acid production by fecal microbiota associated with Clostridial cluster XIVa. This reduction particularly affected and , the two most abundant butyrate-producing bacteria in human feces. VLCKDs preserved the core fecal microbiome, but altered the composition of fecal microbial populations in relation to the plasma metabolome and fecal bile acid composition. In particular, VLCKD-induced weight loss resulted in a reduction in and , an increase in and while not all studies show a decrease in . Although very few studies have analyzed the effects of VLCarbDs and VLCDs on gut microbiota, significant diet-induced changes in fecal microbiota composition have been observed. Further studies are needed. 10.3389/fendo.2021.662591
    Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight. Fragiadakis Gabriela K,Wastyk Hannah C,Robinson Jennifer L,Sonnenburg Erica D,Sonnenburg Justin L,Gardner Christopher D The American journal of clinical nutrition BACKGROUND:With the rising rates of obesity and associated metabolic disorders, there is a growing need for effective long-term weight-loss strategies, coupled with an understanding of how they interface with human physiology. Interest is growing in the potential role of gut microbes as they pertain to responses to different weight-loss diets; however, the ways that diet, the gut microbiota, and long-term weight loss influence one another is not well understood. OBJECTIVES:Our primary objective was to determine if baseline microbiota composition or diversity was associated with weight-loss success. A secondary objective was to track the longitudinal associations of changes to lower-carbohydrate or lower-fat diets and concomitant weight loss with the composition and diversity of the gut microbiota. METHODS:We used 16S ribosomal RNA gene amplicon sequencing to profile microbiota composition over a 12-mo period in 49 participants as part of a larger randomized dietary intervention study of participants consuming either a healthy low-carbohydrate or a healthy low-fat diet. RESULTS:While baseline microbiota composition was not predictive of weight loss, each diet resulted in substantial changes in the microbiota 3-mo after the start of the intervention; some of these changes were diet specific (14 taxonomic changes specific to the healthy low-carbohydrate diet, 12 taxonomic changes specific to the healthy low-fat diet) and others tracked with weight loss (7 taxonomic changes in both diets). After these initial shifts, the microbiota returned near its original baseline state for the remainder of the intervention, despite participants maintaining their diet and weight loss for the entire study. CONCLUSIONS:These results suggest a resilience to perturbation of the microbiota's starting profile. When considering the established contribution of obesity-associated microbiotas to weight gain in animal models, microbiota resilience may need to be overcome for long-term alterations to human physiology. This trial was registered at clinicaltrials.gov as NCT01826591. 10.1093/ajcn/nqaa046
    Plant Extracts in Obesity: A Role of Gut Microbiota. Weng Guangying,Duan Yehui,Zhong Yinzhao,Song Bo,Zheng Jie,Zhang Shiyu,Yin Yulong,Deng Jinping Frontiers in nutrition Obesity has become one of the most serious chronic diseases threatening human health. Its occurrence and development are closely associated with gut microbiota since the disorders of gut microbiota can promote endotoxin production and induce inflammatory response. Recently, numerous plant extracts have been proven to mitigate lipid dysmetabolism and obesity syndrome by regulating the abundance and composition of gut microbiota. In this review, we summarize the potential roles of different plant extracts including mulberry leaf extract, policosanol, cortex moutan, green tea, honokiol, and capsaicin in regulating obesity via gut microbiota. Based on the current findings, plant extracts may be promising agents for the prevention and treatment of obesity and its related metabolic diseases, and the mechanisms might be associated with gut microbiota. 10.3389/fnut.2021.727951
    Gut Microbiota Serves a Predictable Outcome of Short-Term Low-Carbohydrate Diet (LCD) Intervention for Patients with Obesity. Zhang Susu,Wu Peili,Tian Ye,Liu Bingdong,Huang Liujing,Liu Zhihong,Lin Nie,Xu Ningning,Ruan Yuting,Zhang Zhen,Wang Ming,Cui Zongbing,Zhou HongWei,Xie Liwei,Chen Hong,Sun Jia Microbiology spectrum To date, much progress has been made in dietary therapy for obese patients. A low-carbohydrate diet (LCD) has reached a revival in its clinical use during the past decade with undefined mechanisms and debatable efficacy. The gut microbiota has been suggested to promote energy harvesting. Here, we propose that the gut microbiota contributes to the inconsistent outcome under an LCD. To test this hypothesis, patients with obesity or patients who were overweight were randomly assigned to a normal diet (ND) or an LCD group with energy intake for 12 weeks. Using matched sampling, the microbiome profile at baseline and end stage was examined. The relative abundance of butyrate-producing bacteria, including and , was markedly increased after LCD intervention for 12 weeks. Moreover, within the LCD group, participants with a higher relative abundance of at baseline exhibited a better response to LCD intervention and achieved greater weight loss outcomes. Nevertheless, the adoption of an artificial neural network (ANN)-based prediction model greatly surpasses a general linear model in predicting weight loss outcomes after LCD intervention. Therefore, the gut microbiota served as a positive outcome predictor and has the potential to predict weight loss outcomes after short-term LCD intervention. Gut microbiota may help to guide the clinical application of short-term LCD intervention to develop effective weight loss strategies. (This study has been registered at the China Clinical Trial Registry under approval no. ChiCTR1800015156). Obesity and its related complications pose a serious threat to human health. Short-term low-carbohydrate diet (LCD) intervention without calorie restriction has a significant weight loss effect for overweight/obese people. Furthermore, the relative abundance of is a positive outcome predictor of individual weight loss after short-term LCD intervention. Moreover, leveraging on these distinct gut microbial structures at baseline, we have established a prediction model based on the artificial neural network (ANN) algorithm that could be used to estimate weight loss potential before each clinical trial (with Chinese patent number 2021104655623). This will help to guide the clinical application of short-term LCD intervention to improve weight loss strategies. 10.1128/Spectrum.00223-21
    Profound Perturbation of the Metabolome in Obesity Is Associated with Health Risk. Cirulli Elizabeth T,Guo Lining,Leon Swisher Christine,Shah Naisha,Huang Lei,Napier Lori A,Kirkness Ewen F,Spector Tim D,Caskey C Thomas,Thorens Bernard,Venter J Craig,Telenti Amalio Cell metabolism Obesity is a heterogeneous phenotype that is crudely measured by body mass index (BMI). There is a need for a more precise yet portable method of phenotyping and categorizing risk in large numbers of people with obesity to advance clinical care and drug development. Here, we used non-targeted metabolomics and whole-genome sequencing to identify metabolic and genetic signatures of obesity. We find that obesity results in profound perturbation of the metabolome; nearly a third of the assayed metabolites associated with changes in BMI. A metabolome signature identifies the healthy obese and lean individuals with abnormal metabolomes-these groups differ in health outcomes and underlying genetic risk. Specifically, an abnormal metabolome associated with a 2- to 5-fold increase in cardiovascular events when comparing individuals who were matched for BMI but had opposing metabolome signatures. Because metabolome profiling identifies clinically meaningful heterogeneity in obesity, this approach could help select patients for clinical trials. 10.1016/j.cmet.2018.09.022
    Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Liu Ruixin,Hong Jie,Xu Xiaoqiang,Feng Qiang,Zhang Dongya,Gu Yanyun,Shi Juan,Zhao Shaoqian,Liu Wen,Wang Xiaokai,Xia Huihua,Liu Zhipeng,Cui Bin,Liang Peiwen,Xi Liuqing,Jin Jiabin,Ying Xiayang,Wang Xiaolin,Zhao Xinjie,Li Wanyu,Jia Huijue,Lan Zhou,Li Fengyu,Wang Rui,Sun Yingkai,Yang Minglan,Shen Yuxin,Jie Zhuye,Li Junhua,Chen Xiaomin,Zhong Huanzi,Xie Hailiang,Zhang Yifei,Gu Weiqiong,Deng Xiaxing,Shen Baiyong,Xu Xun,Yang Huanming,Xu Guowang,Bi Yufang,Lai Shenghan,Wang Jian,Qi Lu,Madsen Lise,Wang Jiqiu,Ning Guang,Kristiansen Karsten,Wang Weiqing Nature medicine Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota. 10.1038/nm.4358
    Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice. Zhuang Pan,Li Haoyu,Jia Wei,Shou Qiyang,Zhu Ya'er,Mao Lei,Wang Wenqiao,Wu Fei,Chen Xiaoqian,Wan Xuzhi,Wu Yuqi,Liu Xiaohui,Li Yin,Zhu Fanghuan,He Lilin,Chen Jingnan,Zhang Yu,Jiao Jingjing Microbiome BACKGROUND:Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to prevent the development of metabolic disorders. However, their individual role in treating hyperglycemia and the mechanism of action regarding gut microbiome and metabolome in the context of diabetes remain unclear. RESULTS:Supplementation of DHA and EPA attenuated hyperglycemia and insulin resistance without changing body weight in db/db mice while the ameliorative effect appeared to be more pronounced for EPA. DHA/EPA supplementation reduced the abundance of the lipopolysaccharide-containing Enterobacteriaceae whereas elevated the family Coriobacteriaceae negatively correlated with glutamate level, genera Barnesiella and Clostridium XlVa associated with bile acids production, beneficial Bifidobacterium and Lactobacillus, and SCFA-producing species. The gut microbiome alterations co-occurred with the shifts in the metabolome, including glutamate, bile acids, propionic/butyric acid, and lipopolysaccharide, which subsequently relieved β cell apoptosis, suppressed hepatic gluconeogenesis, and promoted GLP-1 secretion, white adipose beiging, and insulin signaling. All these changes appeared to be more evident for EPA. Furthermore, transplantation with DHA/EPA-mediated gut microbiota mimicked the ameliorative effect of DHA/EPA on glucose homeostasis in db/db mice, together with similar changes in gut metabolites. In vitro, DHA/EPA treatment directly inhibited the growth of Escherichia coli (Family Enterobacteriaceae) while promoted Coriobacterium glomerans (Family Coriobacteriaceae), demonstrating a causal effect of DHA/EPA on featured gut microbiota. CONCLUSIONS:DHA and EPA dramatically attenuated hyperglycemia and insulin resistance in db/db mice, which was mediated by alterations in gut microbiome and metabolites linking gut to adipose, liver and pancreas. These findings shed light into the gut-organs axis as a promising target for restoring glucose homeostasis and also suggest a better therapeutic effect of EPA for treating diabetes. Video abstract. 10.1186/s40168-021-01126-6
    Bovine α-lactalbumin hydrolysates ameliorate obesity-associated endotoxemia and inflammation in high-fat diet-fed mice through modulation of gut microbiota. Li Tiange,Gao Jing,Du Min,Mao Xueying Food & function Gut microbiota has been identified as an important factor in the link between nutrient excess and obesity. The aim of this study was to confirm whether bovine α-lactalbumin hydrolysates (LAH) can ameliorate high-fat diet (HFD)-induced endotoxemia and systematic inflammation by modulating the structure of gut microbiota in mice. The results showed that LAH changed the overall structure of gut microbiota in HFD-induced obese mice. LAH increased the Bacteroidetes/Firmicutes ratios and the relative abundance of S24-7, Lachnospiraceae and Blautia. Spearman's correlation analysis revealed significant correlations between the alteration of gut microbiota and obesity-related indexes. LAH decreased the HFD-induced protein expression of G protein-coupled receptor 43 (GPR43) and 41 (GPR41) in the colon tissue. Besides, LAH inhibited the destruction of the gut barrier through the up-regulation of tight junction protein (zonulin/zonula occludens (ZO)-1 and occludin) expression and the decrease of toll-like receptor 4 (TLR4) protein expression in the colon tissue. LAH also significantly reduced the concentration of tumour cell necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in both serum and colon and decreased the level of lipopolysaccharides (LPS) in serum and feces, leading to reduced systematic inflammation and metabolic endotoxemia. In summary, LAH partly modulated the gut microbial composition and structure, and alleviated the obesity-associated inflammation. These findings shed light on bovine α-lactalbumin hydrolysate as a potential functional food ingredient to prevent obesity-related inflammation. 10.1039/c8fo01967c
    Influence of Leptin and Adiponectin Supplementation on Intraepithelial Lymphocyte and Microbiota Composition in Suckling Rats. Grases-Pintó Blanca,Abril-Gil Mar,Castell Margarida,Rodríguez-Lagunas Maria J,Burleigh Stephen,Fåk Hållenius Frida,Prykhodko Olena,Pérez-Cano Francisco J,Franch Àngels Frontiers in immunology Dietary components in early life play a role in both microbiota and intestinal immune system maturation in mammalian species. Adipokines, as endogenously produced hormones from breast milk, may have an impact on this process. The aim of the present study was to establish the influence of leptin and adiponectin supplementation during suckling on the intraepithelial lymphocyte composition, intestinal barrier function, intestinal gene expression, and gut microbiota in rat. For this purpose, newborn Wistar rats were supplemented daily with leptin, adiponectin, or whey protein concentrate during the first 21 days of life. Lymphocyte composition was established by immunofluorescence staining and flow cytometry analysis; intestinal gene expression by real-time PCR and cecal microbiota were analyzed through 16S rRNA gene sequencing. Although leptin and adiponectin were able to increase the Tc TCRαβ and NKT cell proportion, they decreased the NK cell percentage in IEL. Moreover, adipokine supplementation differentially modified CD8 IEL. While the supplementation of leptin increased the proportion of CD8αα IEL (associated to a more intestinal phenotype), adiponectin enhanced that of CD8αβ (related to a peripheral phenotype). Furthermore, both adipokines enhanced the gene expression of TNF-α, MUC-2, and MUC-3, and decreased that of FcRn. In addition, the adipokine supplementations decreased the abundance of the Proteobacteria phylum and the presence of . Moreover, leptin-supplemented animals had lower relative abundance of and a higher proportion of genus, among others. However, supplementation with adiponectin resulted in lower abundance of the genus and a higher proportion of the genus. In conclusion, the supplementation with leptin and adiponectin throughout the suckling period had an impact on both the IEL composition and the gut microbiota pattern, suggesting a modulatory role of these adipokines on the development of intestinal functionality. 10.3389/fimmu.2019.02369
    Randomized Control Trial of Human Recombinant Lactoferrin: A Substudy Reveals Effects on the Fecal Microbiome of Very Low Birth Weight Infants. Sherman Michael P,Sherman Jan,Arcinue Roxanne,Niklas Victoria The Journal of pediatrics UNLABELLED:The purpose of this study is to evaluate the effects of enteral lactoferrin on the fecal microbiome and contrast those influences with the neonatal intensive care unit (NICU) environment. We theorized that lactoferrin and the NICU habitat shape the fecal microbial composition of very preterm infants. Although functions attributed to lactoferrin include intestinal immune system development and emergence of a healthy gut microbiota, evidence is limited. Twenty-one very low birth weight (VLBW <1500 g) infants received twice-daily talactoferrin (TLf, a drug designation for recombinant human lactoferrin) or its excipient by gastric gavage from day 1-28 of life. Twenty-four-hour fecal samples were collected on day 21 of life and compared with fecal operational taxonomy units (OTUs) in treated and control infants in 2 NICUs. Workflow included fecal DNA isolation, generation of amplicons for the V1-V3 region of bacterial 16S ribosomal RNA, and sequencing of a gel-purified multiplex amplicon library using a Roche 454 GS FLX Titanium (Roche, Branford, Connecticut) platform and protocols. Fecal OTUs per infant were higher in NICU 1 vs NICU 2 (P < .001), consistent with fewer antibiotic days (P < .02) and a shorter duration of parenteral nutrition (P < .007) in NICU 1. Proteobacteria and Firmicutes were the major phyla in infants treated with TLf and placebo. Among Enterobacteriaceae, TLf prophylaxis reduced Enterobacter and Klebsiella, but increased Citrobacter in feces of VLBW infants. Citrobacter caused no neonatal infections in the study population. OTUs for Clostridiaceae increased in NICU 1 among infants treated with TLf. Importantly, OTUs of staphylococci were barely detectable in both NICUs among infants fed TLf. Fewer hospital-acquired infections occurred in infants treated with TLf vs controls, although the reduction was seen mostly in coagulase-negative staphylococci-related bloodstream and central line infections (P = .06). TLf modified the fecal microbiome in VLBW infants, but care practices in the NICU habitat also contributed. Future research must establish whether elimination vs enrichment of gut-related microbiota reduces clinically significant hospital-acquired infections and promotes a healthy commensal microflora in the intestines of VLBW infants. TRIAL REGISTRATION:ClinicalTrials.gov: NCT00854633. 10.1016/j.jpeds.2016.02.074
    The Effects of Recombinant Human Lactoferrin on Immune Activation and the Intestinal Microbiome Among Persons Living with Human Immunodeficiency Virus and Receiving Antiretroviral Therapy. Sortino Ornella,Hullsiek Kathy Huppler,Richards Elizabeth,Rupert Adam,Schminke Andrea,Tetekpor Namo,Quinones Mariam,Prosser Rachel,Schacker Tim,Sereti Irini,Baker Jason V The Journal of infectious diseases Lactoferrin modulates mucosal immunity and targets mechanisms contributing to inflammation during human immunodeficiency virus disease. A randomized placebo-controlled crossover clinical trial of recombinant human (rh) lactoferrin was conducted among 54 human immunodeficiency virus-infected participants with viral suppression. Outcomes were tolerability, inflammatory, and immunologic measures, and the intestinal microbiome. The median age was 51 years, and the median CD4+ cell count was 651/µL. Adherence and adverse events did not differ between rh-lactoferrin and placebo. There was no significant effect on plasma interleukin-6 or D-dimer levels, nor on monocyte/T-cell activation, mucosal integrity, or intestinal microbiota diversity. Oral administration of rh-lactoferrin was safe but did not reduce inflammation and immune activation. Clinical Trials Registration: NCT01830595. 10.1093/infdis/jiz042
    A role for whey-derived lactoferrin and immunoglobulins in the attenuation of obesity-related inflammation and disease. Brimelow Rachel E,West Nicholas P,Williams Lauren T,Cripps Allan W,Cox Amanda J Critical reviews in food science and nutrition Obesity is a strong predictive factor in the development of chronic disease and has now superseded undernutrition as a major public health issue. Chronic inflammation is one mechanism thought to link excess body weight with disease. Increasingly, the gut and its extensive population of commensal microflora are recognized as playing an important role in the development of obesity-related chronic inflammation. Obesity and a high fat diet are associated with altered commensal microbial communities and increased intestinal permeability which contributes to systemic inflammation as a result of the translocation of lipopolysaccharide into the circulation and metabolic endotoxemia. Various milk proteins are showing promise in the prevention and treatment of obesity and chronic low-grade inflammation via reductions in visceral fat, neutralization of bacteria at the mucosa and reduced intestinal permeability. In this review, we focus on evidence supporting the potential antiobesogenic and anti-inflammatory effects of bovine whey-derived lactoferrin and immunoglobulins. 10.1080/10408398.2014.995264
    Food restriction followed by refeeding with a casein- or whey-based diet differentially affects the gut microbiota of pre-pubertal male rats. Masarwi Majdi,Solnik Hadas Isaac,Phillip Moshe,Yaron Sima,Shamir Raanan,Pasmanic-Chor Metsada,Gat-Yablonski Galia The Journal of nutritional biochemistry Researchers are gaining an increasing understanding of host-gut microbiota interactions, but studies of the role of gut microbiota in linear growth are scarce. The aim of this study was to investigate the effect of food restriction and refeeding with different diets on gut microbiota composition in fast-growing rats. Young male Sprague-Dawley rats were fed regular rat chow ad libitum (control group) or subjected to 40% food restriction for 36 days followed by continued restriction or ad libitum refeeding for 24 days. Three different diets were used for refeeding: regular vegetarian protein chow or chow in which the sole source of protein was casein or whey. In the control group, the composition of the microbiota remained stable. Food restriction for 60 days led to a significant change in the gut microbiota at the phylum level, with a reduction in the abundance of Firmicutes and an increase in Bacteroidetes and Proteobacteria. Rats refed with the vegetarian protein diet had a different microbiota composition than rats refed the casein- or whey-based diet. Similarities in the bacterial population were found between rats refed vegetarian protein or a whey-based diet and control rats, and between rats refed a casein-based diet and rats on continued restriction. There was a significant strong correlation between the gut microbiota and growth parameters: humerus length, epiphyseal growth plate height, and levels of insulin-like growth factor 1 and leptin. In conclusion, the type of protein in the diet significantly affects the gut microbiota and, thereby, may affect animal's health. 10.1016/j.jnutbio.2017.08.014
    In vitro modulation of gut microbiota by whey protein to preserve intestinal health. Sánchez-Moya T,López-Nicolás R,Planes D,González-Bermúdez C A,Ros-Berruezo G,Frontela-Saseta C Food & function The effect of several types of whey milk - cow, sheep, goat and a mixture of them (60 : 20 : 20, respectively) - was assessed in the human gut microbiota. The prebiotic potential of these substrates was evaluated through in vitro gastrointestinal digestion following faecal batch culture fermentations (mimicking colonic fermentation) for 48 hours, using faeces from normal-weight (NW) and obese (OB) donors. Throughout the fermentation process, pH, gas production, short chain and branched fatty acids (SCFA-BCFA) were measured, as well as the changes of microbiota using qPCR. The pH decreased in all whey samples during the fermentation process. Gas production was higher in all whey samples than in controls, especially at 12 hours (p < 0.05). The diversity of SCFA and BCFA production was significantly different between the donors, in particular cow and mixed whey. Whey milk had a strong prebiotic effect on the gut microbiota of NW and OB donors, showing a significant increase of Bifidobacterium (p < 0.05) with cow, sheep and mixed whey and increase in the Lactobacillus group, particularly in OB donors. Bacteria associated with obesity did not show an increase in any of the groups of donors. Therefore, supplementing a diet with these types of whey can selectively stimulate the growth of probiotic bacteria, enhancing SCFA production, which could improve intestinal disorders. In addition, it may be an interesting approach to the prevention of overweight and obesity and related diseases. Whey milk has a potent prebiotic effect. It can selectively stimulate desirable bacteria and SCFA profile, in both OB and NW donors, contributing to improved intestinal health and reducing obesity. 10.1039/c7fo00197e
    Impact of whey proteins on the systemic and local intestinal level of mice with diet induced obesity. Swiątecka D,Złotkowska D,Markiewicz L H,Szyc A M,Wróblewska B Food & function Obesity is a serious public health problem and being multifactorial is difficult to tackle. Since the intestinal ecosystem's homeostasis is, at least partially, diet-dependent, its modulation may be triggered by food components that are designed to exert a modulatory action leading to a health-promoting effect. Milk whey proteins, are considered as such promising factors since they influence satiation as well as body weight and constitute the source of biologically active peptides which may modulate health status locally and systemically. This way, whey proteins are associated with obesity. Therefore, this paper is aimed at the estimation of the impact of whey proteins using a commercially available whey protein isolate on the physiological response of mice with diet-induced obesity. The physiological response was evaluated on the local-intestinal level, scrutinizing intestinal microbiota as one of the important factors in obesity and on the systemic level, analyzing the response of the organism. Whey proteins brought about the decrease of the fat mass with a simultaneous increase of the lean mass of animals with diet induced obesity, which is a promising, health-promoting effect. Whey proteins also proved to act beneficially helping restore the number of beneficial bifidobacteria in obese animals and decreasing the calorie intake and fat mass as well as the LDL level. Overall, supplementation of the high fat diet with whey proteins acted locally by restoration of the intestinal ecosystem, thus preventing dysbiosis and its effects and also acted systemically by strengthening the organism increasing the lean mass and thus hindering obesity-related detrimental effects. 10.1039/c6fo01311b
    Inulin-type fructans and whey protein both modulate appetite but only fructans alter gut microbiota in adults with overweight/obesity: A randomized controlled trial. Reimer Raylene A,Willis Holly J,Tunnicliffe Jasmine M,Park Heekuk,Madsen Karen L,Soto-Vaca Adriana Molecular nutrition & food research SCOPE:Independently, prebiotics and dietary protein have been shown to improve weight loss and/or alter appetite. Our objective was to determine the effect of combined prebiotic and whey protein on appetite, body composition and gut microbiota in adults with overweight/obesity. METHODS AND RESULTS:In a 12 week, placebo-controlled, double-blind study, 125 adults with overweight/obesity were randomly assigned to receive isocaloric snack bars of: (1) Control; (2) Inulin-type fructans (ITF); (3) Whey protein; (4) ITF + Whey protein. Appetite, body composition and gut microbiota composition/genetic potential were assessed. Compared to Control, body fat was significantly reduced in the Whey protein group at 12 wks. Hunger, desire to eat and prospective food consumption were all lower with ITF, Whey protein and ITF + Whey protein compared to Control at 12 wks. Microbial community structure differed from 0 to 12 wks in the ITF and ITF +Whey Protein groups (i.e. increased Bifidobacterium) but not Whey Protein or Control. Changes in microbial genetic potential were seen between Control and ITF-containing treatments. CONCLUSION:Adding ITF, whey protein or both to snack bars improved several aspects of appetite control. Changes in gut microbiota may explain in part the effects of ITF but likely not whey protein. 10.1002/mnfr.201700484