Gut microbiome and bile acid changes after male rodent sleeve gastrectomy: what comes first?

Abstract

Understanding how a sleeve gastrectomy (SG) achieves metabolic improvement is challenging due to the complex relationship between the liver, bile acid (BA) pool, and gut microbiome. We hypothesized that SG alters the gut microbiome, which then increases the BA pool, leading to metabolic efficacy. We performed fecal material transfer (FMT) from SG or sham mice to surgically naïve mice with an intact microbiome. We evaluated the effect of surgery and FMT on BA-related liver enzymes, BA concentrations, and gut microbiome composition via 16S and metagenomic analysis. SG significantly deflected weight gain compared with sham surgery, 5 ± 2 g versus 10 ± 3 g, respectively (P = 0.004). SG significantly increased the BA pool and decreased liver transcription of slc10a1 (P = 0.04) and cyp8b1 (P = 0.03). Random forest analysis identified several features with significantly increased relative abundance in SG compared with sham mice, including Lactobacillus. Examination of metabolic profiles with metagenomic analysis revealed a BA salt hydrolase produced by the Ligilactobacillus species. FMT of SG stool to surgically naïve mice significantly decreased the BA pool compared with sham FMT (P = 0.034). Unlike SG surgery, we found no effect of SG or sham FMT on bile acid-related enzymes in the liver after 14 wk of treatment. Overall, we propose that the metabolic benefits of SG surgery are related to decreased liver transcription of cyp8b1 and slc10a1 with subsequent increases in the systemic and enterohepatic BA pool, including lithocholic acid. The gut microbiome adapts to the altered BA pool with associated increases in Ligilactobacillus and bile salt hydrolase production.NEW & NOTEWORTHY We propose that the metabolic benefits of sleeve gastrectomy are initiated by decreased liver transcription of cyp8b1 and slc10a1. A notable downstream effect includes changes in systemic bile acid composition and circulation, including increased LCA. An altered gut microbiome after surgery includes increases in Ligilactobacillus that was shown to express a bile salt hydrolase, which could be a contributor to the post-sleeve gastrectomy gut microbiome changes.