Intestinal Gluconeogenesis Shapes Gut Microbiota, Fecal and Urine Metabolome in Mice with Gastric Bypass Surgery

Abstract Background&Aims: Intestinal gluconeogenesis (IGN), gastric bypass (GBP) and gut microbiota positively regulate glucose homeostasis and diet-induced dysmetabolism. GBP modulates gut microbiota but whether IGN intensity could shape it has not been investigated. Methods: To this aim, we studied gut microbiota and microbiome in wild-type and IGN-deficient mice which underwent GBP and were fed on either a normal chow (NC) or a high-fat/high-sucrose (HFHS) diet. We also studied fecal and urine metabolome in NC-fed mice. Results: IGN and GBP had a peculiar effect on both gut microbiota and microbiome, on NC and HFHS diet. IGN inactivation induced Deltaproteobacteria on NC and higher Proteobacteria such as Helicobacter on HFHS diet. GBP induced higher Firmicutes and Proteobacteria on NC-fed WT mice and Firmicutes, Bacteroidetes and Proteobacteria on HFHS-fed WT mice. The combined effect of IGN inactivation and GBP induced higher Actinobacteria on NC and higher Enterococcaceae and Enterobacteriaceae on HFHS diet. A reduction was observed in short-chain fatty acids in fecal (by GBP) and in both fecal and urine (by IGN inactivation) metabolome. Conclusions: IGN and GBP, alone and in combination, shape gut microbiota and microbiome on NC- and HFHS-fed mice, together with a change in fecal and urine metabolome.

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Potential contribution of the gut microbiota to hypoglycemia after gastric bypass surgery

Chinese Medical Journal ◽

10.1097/cm9.0000000000000932 ◽

2020 ◽

Vol 133 (15) ◽

pp. 1834-1843

Author(s):

Li-Yuan Zhou ◽

Ming-Qun Deng ◽

Xin-Hua Xiao

Keyword(s):

Gastric Bypass ◽

Gut Microbiota ◽

Bypass Surgery ◽

Gastric Bypass Surgery ◽

Potential Contribution

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Microbiome transfer between IL-1RI-/- and wild-type mice during high or low-fat feeding alters metabolic tissue functionality but not glucose homeostasis.

Proceedings of The Nutrition Society ◽

10.1017/s0029665120000403 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Jessica C. Ralston ◽

Kathleen A.J. Mitchelson ◽

Gina M. Lynch ◽

Tam T.T. Tran ◽

Conall R. Strain ◽

...

Keyword(s):

Glucose Tolerance ◽

Gut Microbiota ◽

Glucose Homeostasis ◽

Gut Microbiome ◽

Short Chain Fatty Acids ◽

Microbiota Composition ◽

Wild Type ◽

Low Fat ◽

Unifrac Distance ◽

Gut Microbiota Composition

AbstractReduced inflammatory signaling (IL-1RI-/-) alters metabolic responses to dietary challenges (1). Inflammasome deficiency (e.g. IL-18-/-, Asc-/-) can modify gut microbiota concomitant with hepatosteatosis; an effect that was transferable to wild-type (WT) mice by co-housing (2). Taken together, this evidence suggests that links between diet, microbiota and IL-1RI-signaling can influence metabolic health. Our aim was to determine whether IL-1RI-mediated signaling interacted with the gut microbiome to impact metabolic tissue functionality in a diet-specific fashion. Male WT (C57BL/J6) and IL-1RI-/- mice were fed either high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for 24 weeks and were housed i) separately by genotype or ii) with genotypes co-housed together (i.e. isolated vs shared microbial environment; n = 8–10 mice per group). Glucose tolerance and insulin secretion response (1.5 g/kg i.p.), gut microbiota composition and caecal short-chain fatty acids (SCFA) were assessed. Liver and adipose tissue were harvested and examined for triacylglycerol (TAG) formation, cholesterol and metabolic markers (Fasn, Cpt1α, Pparg, Scd1, Dgat1/2), using histology, gas-chromatography and RT-PCR, respectively. Statistical analysis included 1-way or 2-way ANOVA, where appropriate, with Bonferroni post-hoc correction. Co-housing significantly affected gut microbiota composition, illustrated by clustering in PCoA (unweighted UniFrac distance) of co-housed mice but not their single-housed counterparts, on both HFD and LFD. The taxa driving these differences were primarily from Lachnospiraceae and Ruminococcaceae families. Single-housed WT had lower hepatic weight, TAG, cholesterol levels and Fasn despite HFD, an effect lost in their co-housed counterparts, who aligned more to IL-1RI-/- hepatic lipid status. Hepatic Cpt1α was lowest in co-housed WT. Adipose from IL-1RI-/- groups on HFD displayed increased adipocyte size and reduced adipocyte number compared to WT groups, but greater lipogenic potential (Pparg, Scd1, Dgat2) alongside a blunted IL-6 response to pro-inflammatory stimuli (~32%, P = 0.025). Whilst caecal SCFA concentrations were not different between groups, single-housed IL-1RI-/- adipocytes showed greatest sensitivity to SCFA-induced lipogenesis. Interestingly, differences in tissue functionality and gut microbiome occurred despite unaltered glucose tolerance; although there was a trend for phenotypic transfer of body weight via co-housing. For all endpoints examined, similar genotype/co-housing effects were observed for both HFD and LFD with the greatest impacts seen in HFD-fed mice. In conclusion, while the gut microbiome may be an important consideration in dietary interventions, these results question the magnitude of its impact in relation to the IL-1RI-dependent immunometabolism-glucose homeostasis axis.

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The Role of the Gut Microbiota in Sustained Weight Loss Following Roux-en-Y Gastric Bypass Surgery

Obesity Surgery ◽

10.1007/s11695-018-03653-y ◽

2019 ◽

Vol 29 (4) ◽

pp. 1259-1267 ◽

Cited By ~ 9

Author(s):

Farnaz Fouladi ◽

Amanda E. Brooks ◽

Anthony A. Fodor ◽

Ian M. Carroll ◽

Emily C. Bulik-Sullivan ◽

...

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Gut Microbiota ◽

Bypass Surgery ◽

Gastric Bypass Surgery ◽

Sustained Weight Loss

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Depletion of microbiome-derived molecules in the host using Clostridium genetics

10.1101/401489 ◽

2018 ◽

Cited By ~ 3

Author(s):

Chun-Jun Guo ◽

Breanna M. Allen ◽

Kamir J. Hiam ◽

Dylan Dodd ◽

Will van Treuren ◽

...

Keyword(s):

Fatty Acids ◽

Gut Microbiota ◽

Metabolic Pathways ◽

General System ◽

Short Chain Fatty Acids ◽

Wild Type ◽

Bacterial Strains ◽

High Concentrations ◽

Host Tissues ◽

Molecule Production

ABSTRACTThe gut microbiota produce hundreds of molecules that are present at high concentrations in circulation and whose levels vary widely among humans. In most cases, molecule production has not been linked to specific bacterial strains or metabolic pathways, and unraveling the contribution of each molecule to host biology remains difficult. A general system to ‘toggle’ molecules in this pool on/off in the host would enable interrogation of the mechanisms by which they modulate host biology and disease processes. Such a system has been elusive due to limitations in the genetic manipulability of Clostridium and its relatives, the source of many molecules in this pool. Here, we describe a method for reliably constructing clean deletions in a model commensal Clostridium, C. sporogenes (Cs), including multiply mutated strains. We demonstrate the utility of this method by using it to ‘toggle’ off the production of ten Cs-derived molecules that accumulate in host tissues. By comparing mice colonized by wild-type Cs versus a mutant deficient in the production of branched short-chain fatty acids, we discover a previously unknown IgA-modulatory activity of these abundant microbiome-derived molecules. Our method opens the door to interrogating and sculpting a highly concentrated pool of chemicals from the microbiome.

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Long-Term Overconsumption of Fat and Sugar Causes a Partially Reversible Pre-inflammatory Bowel Disease State

Frontiers in Nutrition ◽

10.3389/fnut.2021.758518 ◽

2021 ◽

Vol 8 ◽

Author(s):

Djésia Arnone ◽

Marie Vallier ◽

Sébastien Hergalant ◽

Caroline Chabot ◽

Ndeye Coumba Ndiaye ◽

...

Keyword(s):

Gut Microbiota ◽

Experimental Colitis ◽

High Fat ◽

Sucrose Diet ◽

Normal Chow ◽

Inflammatory Bowel ◽

High Sucrose Diet ◽

High Sucrose ◽

Gut Microbiota Dysbiosis

Nutrition appears to be an important environmental factor involved in the onset of inflammatory bowel diseases (IBD) through yet poorly understood biological mechanisms. Most studies focused on fat content in high caloric diets, while refined sugars represent up to 40% of caloric intake within industrialized countries and contribute to the growing epidemics of inflammatory diseases. Herein we aim to better understand the impact of a high-fat-high-sucrose diet on intestinal homeostasis in healthy conditions and the subsequent colitis risk. We investigated the early events and the potential reversibility of high caloric diet-induced damage in mice before experimental colitis. C57BL/6 mice were fed with a high-fat or high-fat high-sucrose or control diet before experimental colitis. In healthy mice, a high-fat high-sucrose diet induces a pre-IBD state characterized by gut microbiota dysbiosis with a total depletion of bacteria belonging to Barnesiella that is associated with subclinical endoscopic lesions. An overall down-regulation of the colonic transcriptome converged with broadly decreased immune cell populations in the mesenteric lymph nodes leading to the inability to respond to tissue injury. Such in-vivo effects on microbiome and transcriptome were partially restored when returning to normal chow. Long-term consumption of diet enriched in sucrose and fat predisposes mice to colitis. This enhanced risk is preceded by gut microbiota dysbiosis and transcriptional reprogramming of colonic genes related to IBD. Importantly, diet-induced transcriptome and microbiome disturbances are partially reversible after switching back to normal chow with persistent sequelae that may contribute to IBD predisposition in the general population.

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Indication of Bariatric Surgery (Roux-en-Y Gastric Bypass Surgery and Vertical Gastrectomy) in The Older Individuals and implications For Gut Microbiota

Journal of Gastroenterology Pancreatology & Liver Disorders ◽

10.15226/2374-815x/5/1/001111 ◽

2017 ◽

Vol 5 (1) ◽

pp. 1-3

Author(s):

Maria Gabriela Valle Gottlieb ◽

Vilma Maria Junges ◽

Vera Elizabeth Closs

Keyword(s):

Bariatric Surgery ◽

Gastric Bypass ◽

Gut Microbiota ◽

Bypass Surgery ◽

Gastric Bypass Surgery ◽

Older Individuals ◽

Vertical Gastrectomy

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Microbial Adaptation Due to Gastric Bypass Surgery: The Nutritional Impact

Nutrients ◽

10.3390/nu12041199 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1199 ◽

Cited By ~ 1

Author(s):

Silke Crommen ◽

Alma Mattes ◽

Marie-Christine Simon

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Gastric Bypass ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Bypass Surgery ◽

Gastric Bypass Surgery ◽

Liver Fat ◽

Microbial Composition ◽

The Impact

Bariatric surgery leads to sustained weight loss and the resolution of obesity-related comorbidities. Recent studies have suggested that changes in gut microbiota are associated with the weight loss induced by bariatric surgery. Several studies have observed major changes in the microbial composition following gastric bypass surgery. However, there are inconsistencies between the reported alterations in microbial compositions in different studies. Furthermore, it is well established that diet is an important factor shaping the composition and function of intestinal microbiota. However, most studies on gastric bypass have not assessed the impact of dietary intake on the microbiome composition in general, let alone the impact of restrictive diets prior to bariatric surgery, which are recommended for reducing liver fat content and size. Thus, the relative impact of bariatric surgery on weight loss and gut microbiota remains unclear. Therefore, this review aims to provide a deeper understanding of the current knowledge of the changes in intestinal microbiota induced by bariatric surgery considering pre-surgical nutritional changes.

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