The microbiome modulating activity of bile acids

TLDR

Bile acids are potent antibacterial compounds that shape gut microbial ecology. We combined flow cytometry, growth rate measurements, and metabolomics to systematically profile bile acid impacts on the microbiome in vitro and in vivo. The study found that unconjugated bile acids are more antibacterial than conjugated ones, Gram‑positive bacteria are more sensitive than Gram‑negative, certain probiotics and 7α‑dehydroxylating bacteria resist bile acids via glycolysis activation, lithocholic acid is less toxic in the cecal microbiome, bile acids rapidly disrupt bacterial metabolism and membrane integrity, and short‑term exposure alters host metabolism by shifting bacterial community structure, thereby validating prior observations and revealing new bile‑acid–microbiome interaction mechanisms.

Abstract

Bile acids are potent antibacterial compounds and play an important role in shaping the microbial ecology of the gut. Here, we combined flow cytometry, growth rate measurements (OD600), and NMR- and mass spectrometry-based metabolomics to systematically profile the impact of bile acids on the microbiome using in vitro and in vivo models. This study confirmed that (1) unconjugated bile acids possess more potent antibacterial activity than conjugated bile acids; (2) Gram-positive bacteria are more sensitive to bile acids than Gram-negative bacteria; (3) some probiotic bacteria such as Lactobacillus and Bifidobacterium and 7α-dehydroxylating bacteria such as Clostridium scindens show bile acid resistance that is associated with activation of glycolysis. Moreover, we demonstrated that (4) as one of most hydrophobic bile acids, lithocholic acid (LCA) shows reduced toxicity to bacteria in the cecal microbiome in both in vivo and in vitro models; (5) bile acids directly and rapidly affect bacterial global metabolism including membrane damage, disrupted amino acid, nucleotide, and carbohydrate metabolism; and (6) in vivo, short-term exposure to bile acids significantly affected host metabolism via alterations of the bacterial community structure. This study systematically profiled interactions between bile acids and gut bacteria providing validation of previous observation and new insights into the interaction of bile acids with the microbiome and mechanisms related to bile acid tolerance.