Bariatric-induced microbiome changes alter MASLD development in association with changes in the innate immune system

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) affects nearly 25% of the population and is the leading cause for liver-related mortality. Bariatric surgery is a well-known treatment for MASLD and obesity. Understanding the fundamental mechanisms by which bariatric surgery can alter MASLD can lead to new avenues of therapy and research. Previous studies have identified the microbiome's role in bariatric surgery and in inflammatory immune cell populations. The host innate immune system modulates hepatic inflammation and fibrosis, and thus the progression of MASLD. The precise role of immune cell types in the pathogenesis of MASLD remains an active area of investigation. The aim of this study was to understand the interplay between microbiota composition post-bariatric surgery and the immune system in MASLD.MethodsEighteen morbidly obese females undergoing sleeve gastrectomy were followed pre-and post-surgery. Stool from four patients, showing resolved MASLD post-surgery with sustained weight loss, was transplanted into antibiotic treated mice. Mice received pre-or post-surgery stool and were fed a standard or high-fat diet. Bodyweight, food intake, and physiological parameters were tracked weekly. Metabolic parameters were measured post-study termination.ResultsThe human study revealed that bariatric surgery led to significant weight loss (p > 0.05), decreased inflammatory markers, and improved glucose levels six months post-surgery. Patients with weight loss of 20% or more showed distinct changes in blood metabolites and gut microbiome composition, notably an increase in Bacteroides. The mouse model confirmed surgery-induced microbiome changes to be a major factor in the reduction of markers and attenuation of MASLD progression. Mice receiving post-surgery fecal transplants had significantly less weight gain and liver steatosis compared to pre-surgery recipients. There was also a significant decrease in inflammatory cytokines interferon gamma, interleukin 2, interleukin 15, and mig. This was accompanied by alterations in liver immunophenotype, including an increase in natural killer T cells and reduction of Kupfer cells in the post-surgery transplant group.DiscussionOur findings suggest surgery induced microbial changes significantly reduce inflammatory markers and fatty liver progression. The results indicate a potential causal link between the microbiome and the host immune system, possibly mediated through modulation of liver NKT and Kupffer cells

Surgically Induced Changes in Gut Microbiome and Hedonic Eating as Related to Weight Loss

ObjectiveWeight loss surgery results in significant changes in the anatomy, function, and intraluminal environment of the gastrointestinal tract affecting the gut microbiome. Although bariatric surgery results in sustained weight loss, decreased appetite, and hedonic eating, it is unknown whether the surgery-induced alterations in gut microbiota play a role in the observed changes in hedonic eating. We explored the following hypotheses: (1) laparoscopic sleeve gastrectomy (LSG) results in changes in gut microbial composition; (2) alterations in gut microbiota are related to weight loss; (3) alterations in gut microbiome are associated with changes in appetite and hedonic eating.MethodsEight obese women underwent LSG. Their body mass index, body fat mass, food intake, hunger, hedonic eating scores, and stool samples were obtained at baseline and 1-month postsurgery. 16S ribosomal RNA gene sequencing was performed on stool samples. DESeq2 changes in microbial abundance. Multilevel-sparse partial least squares discriminant analysis was applied to genus-level abundance for discriminative microbial signatures.ResultsLSG resulted in significant reductions in body mass index, food intake, and hedonic eating. A microbial signature composed of five bacterial genera discriminated between pre- and postsurgery status. Several bacterial genera were significantly associated with weight loss (Bilophila, q = 3E-05; Faecalibacterium q = 4E-05), lower appetite (Enterococcus, q = 3E-05), and reduced hedonic eating (Akkermansia, q = .037) after surgery.ConclusionsIn this preliminary analysis, changes in gut microbial abundance discriminated between pre- and postoperative status. Alterations in gut microbiome were significantly associated with weight loss and with reduced hedonic eating after surgery; however, a larger sample is needed to confirm these findings

Improvement in Uncontrolled Eating Behavior after Laparoscopic Sleeve Gastrectomy Is Associated with Alterations in the Brain–Gut–Microbiome Axis in Obese Women

BackgroundBariatric surgery is proven to change eating behavior and cause sustained weight loss, yet the exact mechanisms underlying these changes are not clearly understood. We explore this in a novel way by examining how bariatric surgery affects the brain-gut-microbiome (BGM) axis.MethodsPatient demographics, serum, stool, eating behavior questionnaires, and brain magnetic resonance imaging (MRI) were collected before and 6 months after laparoscopic sleeve gastrectomy (LSG). Differences in eating behavior and brain morphology and resting-state functional connectivity in core reward regions were correlated with serum metabolite and 16S microbiome data.ResultsLSG resulted in significant weight loss and improvement in maladaptive eating behaviors as measured by the Yale Food Addiction Scale (YFAS). Brain imaging showed a significant increase in brain volume of the putamen (p.adj < 0.05) and amygdala (p.adj < 0.05) after surgery. Resting-state connectivity between the precuneus and the putamen was significantly reduced after LSG (p.adj = 0.046). This change was associated with YFAS symptom count. Bacteroides, Ruminococcus, and Holdemanella were associated with reduced connectivity between these areas. Metabolomic profiles showed a positive correlation between this brain connection and a phosphatidylcholine metabolite.ConclusionBariatric surgery modulates brain networks that affect eating behavior, potentially through effects on the gut microbiota and its metabolites

Microbial changes from bariatric surgery alters glucose-dependent insulinotropic polypeptide and prevents fatty liver disease.

Bariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes

Microbial changes from bariatric surgery alters glucose-dependent insulinotropic polypeptide and prevents fatty liver disease

ABSTRACTBariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes