A Subset of Roux-en-Y Gastric Bypass Bacterial Consortium Colonizes the Gut of Nonsurgical Rats without Inducing Host-Microbe Metabolic Changes

Liu, Zhigang; Coales, Isabelle; Penney, Nicholas; McDonald, Julie A. K.; Phetcharaburanin, Jutarop; Seyfried, Florian; Li, Jia V.

doi:10.1128/msystems.01047-20

Cited by 7 publications

(9 citation statements)

References 48 publications

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“…A potential explanation for these discrepancies could be the different frequencies of bacterial inoculations and/or the different duration of body weight measurements between studies. Nevertheless, our findings are consistent with the majority of studies showing no effect of gut microbiota transfer from RYGB-treated rats ( 22 ) or patients ( 14 , 23 , 24 ) on body weight in GF mice or mice with prior depletion of the gut microbiota from antibiotic treatment ( 14 , 23 ), rats with prior depletion of the gut microbiota from antibiotic treatment ( 22 ), or patients with obesity ( 24 ). The findings of the present study thus support the idea that members of the gut microbiota are important contributors to improved glycemic control rather than to weight loss after metabolic surgery, especially in humans ( 14 , 23 ).…”

Section: Observationsupporting

confidence: 91%

Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery

et al. 2023

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Section: Observationsupporting

confidence: 91%

Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery

et al. 2023

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“…9 There is evidence for a causal role for gut microbes in lowering fat mass after bariatric surgery in some preclinical models. [9][10][11] It is known that gut microbes influence host metabolism and can contribute to features of…”

Section: Introductionmentioning

confidence: 99%

“…Conserved shifts in gut microbiota after gastric bypass surgery in humans can promote weight loss and fat loss when transferred to germ-free mice 9. There is evidence for a causal role for gut microbes in lowering fat mass after bariatric surgery in some preclinical models 9–11. It is known that gut microbes influence host metabolism and can contribute to features of the metabolic syndrome beyond obesity, including insulin resistance and glycaemic control 12 13.…”

Section: Introductionmentioning

confidence: 99%

Human gut microbiota after bariatric surgery alters intestinal morphology and glucose absorption in mice independently of obesity

Anhê

Zhang

Choi

et al. 2022

Gut

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ObjectiveBariatric surgery is an effective treatment for type 2 diabetes (T2D) that changes gut microbial composition. We determined whether the gut microbiota in humans after restrictive or malabsorptive bariatric surgery was sufficient to lower blood glucose.DesignWomen with obesity and T2D had biliopancreatic diversion with duodenal switch (BPD-DS) or laparoscopic sleeve gastrectomy (LSG). Faecal samples from the same patient before and after each surgery were used to colonise rodents, and determinants of blood glucose control were assessed.ResultsGlucose tolerance was improved in germ-free mice orally colonised for 7 weeks with human microbiota after either BPD-DS or LSG, whereas food intake, fat mass, insulin resistance, secretion and clearance were unchanged. Mice colonised with microbiota post-BPD-DS had lower villus height/width and crypt depth in the distal jejunum and lower intestinal glucose absorption. Inhibition of sodium-glucose cotransporter (Sglt)1 abrogated microbiota-transmissible improvements in blood glucose control in mice. In specific pathogen-free (SPF) rats, intrajejunal colonisation for 4 weeks with microbiota post-BPD-DS was sufficient to improve blood glucose control, which was negated after intrajejunal Sglt-1 inhibition. Higher Parabacteroides and lower Blautia coincided with improvements in blood glucose control after colonisation with human bacteria post-BPD-DS and LSG.ConclusionExposure of rodents to human gut microbiota after restrictive or malabsorptive bariatric surgery improves glycaemic control. The gut microbiota after bariatric surgery is a standalone factor that alters upper gut intestinal morphology and lowers Sglt1-mediated intestinal glucose absorption, which improves blood glucose control independently from changes in obesity, insulin or insulin resistance.

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“…Fecal metabolomic profiles differentiate between responders and failures. We observed a clear difference in the fecal metabolomic profiles between trial responders (n = 19) and failures (n = 12) among all patients at all time points (R2 = 0.613, Q2 = 0.220, P < 0.0001). This OPLS-DA model and the correlations between metabolites and the primary trial outcome with a correlation coefficient (r) greater than or equal to 0.50 are presented in Figure 3A.…”

Section: Resultsmentioning

confidence: 85%

Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial

Kragsnaes,

Miguens Blanco,

Mullish

et al. 2023

ACR Open Rheumatology

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ObjectiveWe investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate‐treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT).MethodsThis exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate‐to‐high peripheral PsA disease activity, despite at least 3 months of methotrexate‐treatment, were included in a 26‐week, double‐blind, 1:1 randomized, sham‐controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose‐to‐mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1H Nuclear Magnetic Resonance.ResultsTrial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017‐0.33]) vs. 0.012 [0‐0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N‐acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02).ConclusionIntestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.

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A Subset of Roux-en-Y Gastric Bypass Bacterial Consortium Colonizes the Gut of Nonsurgical Rats without Inducing Host-Microbe Metabolic Changes

Abstract: Roux-en-Y gastric bypass (RYGB) surgery results in a long-term gut bacterial shift toward Gammaproteobacteria in both patients and rodents. The contribution of this compositional shift, or the RYGB bacterial consortium, to the metabolic benefit of the surgery remains debatable.

Cited by 7 publications

References 48 publications

Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery

Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery

Human gut microbiota after bariatric surgery alters intestinal morphology and glucose absorption in mice independently of obesity

Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial

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