Gut microbial structural variations as determinants of human bile acid metabolism

Abstract

Bile acids (BAs) facilitate intestinal fat absorption and act as important signaling molecules in host-gut microbiota crosstalk. BA-metabolizing pathways in the microbial community have been identified, but how the highly variable genomes of gut bacteria interact with host BA metabolism remains largely unknown. We characterized 8,282 structural variants (SVs) of 55 bacterial species in the gut microbiomes of 1,437 individuals from two Dutch cohorts and performed a systematic association study with 39 plasma BA parameters. Both variations in SV-based continuous genetic makeup and discrete subspecies showed correlations with BA metabolism. Metagenome-wide association analysis identified 797 replicable associations between bacterial SVs and BAs and SV regulators that mediate the effects of lifestyle factors on BA metabolism. This is the first large-scale microbial genetic association analysis to demonstrate the impact of bacterial SVs on human BA composition, and highlights the potential of targeting gut microbiota to regulate BA metabolism through lifestyle intervention.

Antibiotic‐Induced Gut Microbiota Dysbiosis Modulates Host Transcriptome and m6A Epitranscriptome via Bile Acid Metabolism

“…The diversity and composition of the gut microbiome have been studied for over a decade, but their precise roles in influencing host physiology and maintaining tissue homeostasis are still under intense investigation. [32,33] In this study, we found that ampicillin-induced gut dysbiosis led to unbalanced Firmicutes/Bacteroidetes ratios and reduced production of secondary bile acids. Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids to exert biological functions.…”

Discovery, diversity and functional associations of crAss-like phages in human gut metagenomes from four Dutch cohorts

“…Next, we explored associations between the abundance of crAss-like phages and structural variants (SVs) in bacterial genomes (Wang et al, 2021; Zeevi et al, 2019). Based on the collection of samples from the three independent cohorts LLD, 300OB and IBD, we detected 7,999 deletion structural variants (dSVs, genome segments absent in 25% to 75% samples) and 3,559 variable structural variants (vSVs, genome segments absent in < 25% samples).…”