Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption

Abstract

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.

Figures

Figure 1

Alterations in the main phyla Bacteroidetes and Firmicutes of the human intestinal microbiota after three and six months of weight loss therapy for morbid obesity: (a) laparoscopic sleeve gastrectomy (LSG) and (b) very low calorie diet (VLCD).

Figure 2

Human gut microbiota changes on the taxonomic species level induced by weight loss therapy for morbid obesity: (a) laparoscopic sleeve gastrectomy (LSG) and (b) very low calorie diet (VLCD). Shown are all bacterial species for which changes were significantly defined as a P(corr) > 0.75 or <−0.75 derived from OPLS-DA models.

Figure 3

KEGG orthologues representing the microbial metabolic capacity of the human gut microbiota for butyrate fermentation after weight loss therapy for morbid obesity: (a) laparoscopic sleeve gastrectomy (LSG) and (b) very low calorie diet (VLCD). Shown are three KEGG orthologues (K00074, K00929, and K00626) with key functions in the fermentation pathway denoted in the KEGG map extract on the right bottom corner.

Figure 4

Faecal excretion of middle- and long chain nonesterified fatty acids (NEFAs): (a) mean fold changes of NEFA excretion 6 months after weight loss therapy for morbid obesity (light grey: laparoscopic sleeve gastrectomy (LSG) and dark grey: very low calorie diet (VLCD)). (b) Summed faecal concentrations of NEFAs in the course after laparoscopic sleeve gastrectomy (LSG).

Figure 5

Faecal bile acids alterations six months after laparoscopic sleeve gastrectomy (LSG). OPLS-DA coefficient plot showing the increase or decrease in concentration for each of the bile acids identified by targeted profiling. The model compares 6 months post-LSG with preoperative values. The coefficient along the y-axis is a measure of both the magnitude and direction of change of bile acid concentrations. ∗ indicates which metabolites contribute significantly to class discrimination (pre- to post-LSG; P(corr) > 0.75 and P(corr) < −0.75) corresponding to the color scale code shown on the left hand. Error bars derived from calculation of Jack-knifing uncertainty measures. (b) Suggested impact of LSG on extrahepatic bile acid circulation based on the presented data.