Fecal metagenomics and metabolomics reveal gut microbial changes after bariatric surgery

Abstract

Background: Evidence from longitudinal patient studies regarding gut microbial changes after bariatric surgery is limited.

Objective: To examine intraindividual changes in fecal microbiome and metabolites among patients undergoing Roux-en-Y gastric bypass or vertical sleeve gastrectomy.

Setting: Observational study.

Methods: Twenty patients were enrolled and provided stool samples before and 1 week, 1 month, and/or 3 months after surgery. Shallow shotgun metagenomics and untargeted fecal metabolomics were performed. Zero-inflated generalized additive models and linear mixed models were applied to identify fecal microbiome and metabolites changes, with adjustment for potential confounders and correction for multiple testing.

Results: We enrolled 16 women and 4 men, including 16 white and 4 black participants (median age = 45 years; presurgery body mass index = 47.7 kg/m²). Ten patients had Roux-en-Y gastric bypass, 10 had vertical sleeve gastrectomy, and 14 patients provided postsurgery stool samples. Of 47 samples, median sequencing depth was 6.3 million reads and 1073 metabolites were identified. Microbiome alpha-diversity increased after surgery, especially at 3 months. Significant genus-level changes included increases in Odoribacter, Streptococcus, Anaerotruncus, Alistipes, Klebsiella, and Bifidobacterium, while decreases in Bacteroides, Coprocosccus, Dorea, and Faecalibacterium. Large increases in Streptococcus, Akkermansia, and Prevotella were observed at 3 months. Beta-diversity and fecal metabolites were also changed, including reduced caffeine metabolites, indoles, and butyrate.

Conclusions: Despite small sample size and missing repeated samples in some participants, our pilot study showed significant postsurgery changes in fecal microbiome and metabolites among bariatric surgery patients. Future large-scale, longitudinal studies are warranted to investigate gut microbial changes and their associations with metabolic outcomes after bariatric surgery.

Keywords: Bariatric surgery; Fecal metabolomics; Gut microbiota; Longitudinal patient cohort; Metagenomics.

Fig. 1.

Fecal microbiome alpha- and beta-diversity indices before and after bariatric surgery. (a) Shannon index (0 = presurgery; 7 = 1 wk; 30 = 1 mo; 90 = 3 mo after surgery; linear mixed model, P = .004 for pre versus 1 wk; .54 for pre versus 1 mo; .04 for pre versus 3 mo). (b) Bray-Curtis distance (principle co-ordinates analysis plot; red = presurgery; blue = postsurgery; permutation multivariate analysis of variance P = .015)