scholarly journals Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota

2020 ◽  
Vol 7 (9) ◽  
Author(s):  
Stéphane Isnard ◽  
John Lin ◽  
Brandon Fombuena ◽  
Jing Ouyang ◽  
Thibault V Varin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Polycystic Ovary ◽  
Pilot Trial ◽  
Metformin Treatment ◽  
Microbiota Composition ◽  
Markers Of Inflammation ◽  
Increased Risk ◽  
Stool Samples ◽  
Anti Inflammatory ◽  
Gut Microbiota Composition

Abstract Background People with HIV (PWH) taking antiretroviral therapy (ART) may experience weight gain, dyslipidemia, increased risk of non-AIDS comorbidities, and long-term alteration of the gut microbiota. Both low CD4/CD8 ratio and chronic inflammation have been associated with changes in the gut microbiota of PWH. The antidiabetic drug metformin has been shown to improve gut microbiota composition while decreasing weight and inflammation in diabetes and polycystic ovary syndrome. Nevertheless, it remains unknown whether metformin may benefit PWH receiving ART, especially those with a low CD4/CD8 ratio. Methods In the Lilac pilot trial, we recruited 23 nondiabetic PWH receiving ART for more than 2 years with a low CD4/CD8 ratio (<0.7). Blood and stool samples were collected during study visits at baseline, after a 12-week metformin treatment, and 12 weeks after discontinuation. Microbiota composition was analyzed by 16S rDNA gene sequencing, and markers of inflammation were assessed in plasma. Results Metformin decreased weight in PWH, and weight loss was inversely correlated with plasma levels of the satiety factor GDF-15. Furthermore, metformin changed the gut microbiota composition by increasing the abundance of anti-inflammatory bacteria such as butyrate-producing species and the protective Akkermansia muciniphila. Conclusions Our study provides the first evidence that a 12-week metformin treatment decreased weight and favored anti-inflammatory bacteria abundance in the microbiota of nondiabetic ART-treated PWH. Larger randomized placebo-controlled clinical trials with longer metformin treatment will be needed to further investigate the role of metformin in reducing inflammation and the risk of non-AIDS comorbidities in ART-treated PWH.

Changes in the gut microbiota of morbidly obese patients after laparoscopic sleeve gastrectomy

2021 ◽  
Author(s):  
Alev Kural ◽  
Imran Khan ◽  
Hakan Seyit ◽  
Tuba R Caglar ◽  
Pınar Toklu ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Gut Microbiota ◽  
Laparoscopic Sleeve Gastrectomy ◽  
Amplicon Sequencing ◽  
Morbidly Obese ◽  
Microbiota Composition ◽  
16S Amplicon Sequencing ◽  
Before And After ◽  
Stool Samples ◽  
Gut Microbiota Composition

Aims: Permanent treatment of morbid obesity with medication or diet is nearly impossible. Laparoscopic sleeve gastrectomy (LSG) is becoming a widely accepted treatment option. This study profiled and compared gut microbiota composition before and after LSG. Methods & results: A total of 54 stool samples were collected from 27 morbidly obese individuals before and after LSG. The gut microbiota was profiled with 16S amplicon sequencing. After LSG, patients demonstrated a significant decrease (p < 0.001) in BMI and an increase in bacterial diversity. An increased Firmicutes/Bacteroidetes ratio was also noticed after LSG. The families Prevotellaceae and Veillonellaceae predominated in preoperative samples but were markedly lowered after LSG. A marked increase in Akkermansia, Alistipes, Streptococcus, Ruminococcus and Parabacteroides was observed after LSG. Conclusion: In addition to lowering BMI, LSG remodeled gut microbiota composition.

scholarly journals Comparative Analysis of Fecal Microbiota Composition Between Rheumatoid Arthritis and Osteoarthritis Patients

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 748 ◽  
Author(s):  
Jin-Young Lee ◽  
Mohamed Mannaa ◽  
Yunkyung Kim ◽  
Jehun Kim ◽  
Geun-Tae Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Stool Samples ◽  
Gut Microbiota Composition

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.

scholarly journals Metformin Exerts Anti-inflammatory and Mucus Barrier Protective Effects by Enriching Akkermansia muciniphila in Mice With Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Haoran Ke ◽  
Fang Li ◽  
Wenlin Deng ◽  
Zitong Li ◽  
Siqi Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Treated Group ◽  
Protective Effects ◽  
Microbiota Composition ◽  
16S Rrna Analysis ◽  
Akkermansia Muciniphila ◽  
Anti Inflammatory ◽  
Mucus Barrier ◽  
Gut Microbiota Composition

The present study aimed to determine if metformin exerts anti-inflammatory and mucus-protective effects via the gut microbiota. Metformin has extensive benefits including anti-inflammatory effects. Previous studies showed that metformin changed the gut microbiota composition and increases the number of goblet cells. Intestinal dysbiosis and goblet cell depletion are important features of ulcerative colitis (UC). The underlying mechanism and whether metformin can improve the mucus barrier in UC remain unclear. Metformin (400 mg/kg/day) was administered to mice with dextran sulfate sodium (DSS)-induced UC for 2 wk to investigate the effects of metformin on the intestinal mucus barrier. The gut microbiota was depleted, using antibiotics, to explore its role in the mucus-protecting effects of metformin. Akkermansia muciniphila (A. muciniphila), which was enriched in metformin-treated mice, was administered to mice to investigate the effects of the bacteria on UC and the mucus barrier. Metformin attenuated DSS-induced UC in mice, as evidenced by the alleviation of diarrhea, hematochezia, and the decrease in body weight. The expression of mucin2, a prominent mucus barrier protein, was increased in the metformin-treated group compared to the DSS-treated group. Furthermore, fecal 16S rRNA analysis showed that metformin treatment changed the gut microbiota composition by increasing the relative abundance of Lactobacillus and Akkermansia species while decreasing Erysipelatoclostridium at the genus level. Antibiotic treatment partly abolished the anti-inflammatory and mucus-protecting effects of metformin. Administration of A. muciniphila alleviated the colonic inflammation and mucus barrier disruption. Metformin alleviated DSS-induced UC in mice and protected against cell damage via affecting the gut microbiota, thereby providing a new mechanism for the therapeutic effect of metformin in patients with UC. This study also provides evidence that A. muciniphila as a probiotic has potential benefits for UC.

Gut microbiota dysbiosis in polycystic ovary syndrome: association with obesity — a preliminary report

2020 ◽  
Vol 98 (11) ◽  
pp. 803-809 ◽  
Author(s):  
Yuanjiao Liang ◽  
Qi Ming ◽  
Jinlan Liang ◽  
Yan Zhang ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Gut Microbiota ◽  
Polycystic Ovary ◽  
Alpha Diversity ◽  
Shannon Index ◽  
Normal Weight ◽  
Microbiota Composition ◽  
Ovary Syndrome ◽  
Gut Microbiota Dysbiosis ◽  
Gut Microbiota Composition

The objective was to explore if and how the microbiota changed in polycystic ovary syndrome (PCOS) women compared with healthy women. Eight obese PCOS (PO group), 10 nonobese PCOS (PN group), and nine healthy normal weight women (control) (C group) were enrolled. Insulin (INS), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), and dehydroepiandrosterone (DHEA) were detected with radioimmunoassay. Antimullerian hormone (AMH), fasting glucose, and hemoglobin A1c (HbA1c) were determined by a chemiluminescence immunoassay, glucose oxidase method, and HPLC, respectively. Gut microbiota composition was evaluated by PCR. Alpha diversity was assessed using Chao1 and the Shannon index. PCOS women showed significantly higher T, LH, and LH/FSH and lower FSH levels than the C group (p < 0.05). The AMH level was significantly higher in the PO than in the PN group (p < 0.05). The PO group presented a significantly higher fasting INS level and HMOA-IR scores than the other groups, lower observed SVs and alpha diversity than the C group, higher beta diversity than the PN group (p < 0.05), and decreased abundances of genera (mainly butyrate producers). Regression analysis showed that decreased abundances of several genera were correlated with higher circulating T and impaired glucose metabolism. PCOS is associated with changes in the gut microbiota composition. Obesity has a driving role in the development of dysbiotic gut microbiota in PCOS.

Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322599
Author(s):  
Hsin-Chih Lai ◽  
Tzu-Lung Lin ◽  
Ting-Wen Chen ◽  
Yu-Lun Kuo ◽  
Chih-Jung Chang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Chronic Obstructive ◽  
Microbiota Composition ◽  
Active Components ◽  
Toll Like Receptor 4 ◽  
Obstructive Pulmonary Disease ◽  
Anti Inflammatory ◽  
Gut Microbiota Composition

ObjectiveChronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.DesignA murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.ResultsGut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.ConclusionThe gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

scholarly journals Gut microbiota composition strongly correlates to peripheral insulin sensitivity in obese men but not in women

2017 ◽  
Vol 8 (4) ◽  
pp. 557-562 ◽  
Author(s):  
J. Most ◽  
G.H. Goossens ◽  
D. Reijnders ◽  
E.E. Canfora ◽  
J. Penders ◽  
...  
Keyword(s):  
Body Composition ◽  
Insulin Sensitivity ◽  
Gut Microbiota ◽  
Saturated Fat ◽  
Microbiota Composition ◽  
Peripheral Insulin Sensitivity ◽  
Markers Of Inflammation ◽  
Obese Subjects ◽  
And Gender ◽  
Gut Microbiota Composition

Gut microbiota composition may play an important role in the development of obesity-related comorbidities. However, only few studies have investigated gender-differences in microbiota composition and gender-specific associations between microbiota or microbial products and insulin sensitivity. Insulin sensitivity (hyperinsulinemic-euglycemic clamp), body composition (dual energy X-ray absorptiometry), substrate oxidation (indirect calorimetry), systemic inflammatory markers and microbiota composition (PCR) were determined in male (n=15) and female (n=14) overweight and obese subjects. Bacteroidetes/Firmicutes-ratio was higher in men than in women (P=0.001). Bacteroidetes/Firmicutes-ratio was inversely related to peripheral insulin sensitivity only in men (men: P=0.003, women: P=0.882). This association between Bacteroidetes/Firmicutes-ratio and peripheral insulin sensitivity did not change after adjustment for dietary fibre and saturated fat intake, body composition, fat oxidation and markers of inflammation. Bacteroidetes/Firmicutes-ratio was not associated with hepatic insulin sensitivity. Men and women differ in microbiota composition and its impact on insulin sensitivity, implying that women might be less sensitive to gut microbiota-induced metabolic aberrations than men. This trial was registered at clinicaltrials.gov as NCT02381145.

scholarly journals Alleviative Effects of Exopolysaccharide Produced by Lactobacillus helveticus KLDS1.8701 on Dextran Sulfate Sodium-Induced Colitis in Mice

2021 ◽  
Vol 9 (10) ◽  
pp. 2086
Author(s):  
Yin Liu ◽  
Shujuan Zheng ◽  
Jiale Cui ◽  
Tingting Guo ◽  
Jingtao Zhang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Lactobacillus Helveticus ◽  
Mucosal Barrier ◽  
Microbiota Composition ◽  
Mucosal Barrier Function ◽  
Anti Inflammatory ◽  
Gut Microbiota Composition

Ulcerative colitis (UC) is a non-specific chronic inflammatory disease with lesions located in the colon and rectum. The aim of this study was to evaluate the anti-inflammatory effects of exopolysaccharide-1 (EPS-1) isolated by L. helveticus KLDS1.8701 on UC. The anti-inflammatory effects of EPS-1 were studied using dextran sulphate sodium (DSS)-induced UC model. In vivo results showed that EPS-1 administration significantly ameliorated weight loss, colon shortening, disease activity index (DAI) score, myeloperoxidase (MPO) activity, and colon tissue damage. In addition, EPS-1 administration significantly decreased the levels of pro-inflammatory cytokines and increased levels of anti-inflammatory cytokines. Meanwhile, EPS-1 administration significantly up-regulated the expression of tight junction proteins and mucin. Furthermore, EPS-1 administration modulated gut microbiota composition caused by DSS and increased the short-chain fatty acids (SCFAs) levels. Collectively, our study showed the alleviative effects of EPS- isolated by L. helveticus KLDS1.8701 on DSS-induced UC via alleviating intestinal inflammation, improving mucosal barrier function, and modulating gut microbiota composition.

scholarly journals Chlorogenic Acid Alleviates Colon Mucosal Damage Induced by a High-Fat Diet via Gut Microflora Adjustment to Increase Short-Chain Fatty Acid Accumulation in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
M. Gui Xie ◽  
Y. Quan Fei ◽  
Y. Wang ◽  
W. Yan Wang ◽  
Z. Wang
Keyword(s):  
Gut Microbiota ◽  
Chlorogenic Acid ◽  
Butyric Acid ◽  
High Fat Diet ◽  
Intestinal Inflammation ◽  
Short Chain ◽  
Microbiota Composition ◽  
High Fat ◽  
Anti Inflammatory ◽  
Gut Microbiota Composition

A high-fat diet (HFD) has been previously associated with the development of diseases such as chronic colitis. While chlorogenic acid (CGA) is known to exhibit potent antioxidant, antibacterial, and anti-inflammatory properties, little is known about its effects on intestinal inflammation. In this study, we investigated the effects of CGA on intestinal inflammation in an HFD-induced obesity rat model and assessed whether these effects were related to changes in gut microbiota composition. This was achieved by examining physiological and biochemical indicators, the liver transcriptome, and the structure of the fecal microflora. CGA treatment significantly reduced HFD-induced internal organ weight gain, promoted colon tissue repair, downregulated the expression of inflammatory cytokines, and promoted the accumulation of the tight junction protein. KEGG enrichment analysis of differentially expressed genes, applied to data from the RNA-seq of rat liver tissue, revealed that CGA treatment significantly affected amino acid and lipid metabolism in the liver. Furthermore, CGA decreased the abundance of bacteria belonging to the genera Blautia, Sutterella, and Akkermansia and increased butyric acid levels, which were positively correlated with the abundance of Ruminococcus (butyric acid producer). Moreover, the beneficial changes observed in the HFD group were not as pronounced as those in the CGA treatment group. In summary, CGA can alleviate colitis in HFD-induced obesity through its anti-inflammatory effects associated with changes in gut microbiota composition and an increase in the production of short-chain fatty acids and thus can be used as a potential drug for the treatment of this pathology.

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