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.
Seeding and development of the gut ecosystem are crucial for health, both in childhood and later in life. While the composition of infant gut bacterial communities has been described, the composition and origin of the infant gut virome remains under-studied. Here, we explore mother-to-infant transmission of bacteria and viruses in 30 mother–infant pairs in a longitudinal collection of faecal samples taken during pregnancy and the first 3 months after birth. We demonstrate that infant bacterial strains resemble maternal strains more than those of unrelated mothers. We quantify viromes using a complementary approach examining both total metagenomes and viral metagenomes. The virome composition is highly consistent between viral and total metagenomes. The infant gut viromes are dominated by active temperate bacteriophages, which are more abundant in infants than mothers (p-value=7.2e-06). We observe that the proportion of shared viruses between maternal and infant gut is only 11.3% when considering the active virome fraction alone, but increases to 37.6% when taking into account temperate phages in the form of prophages. These findings indicate that viruses are vertically transmitted from mothers to infants early in life and that pioneering phages can reach the infant gut via vertical transmission of their bacterial hosts.
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