University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen 9713AV, the Netherlands; University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen 9713AV, the Netherlands.
Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen 6500HB, the Netherlands.
Cell Host Microbe. 2021 Dec 8;29(12):1802-1814.e5. doi: 10.1016/j.chom.2021.11.003. Epub 2021 Nov 29.
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 it remains largely unknown how the highly variable genomes of gut bacteria interact with host BA metabolism. We characterized 8,282 structural variants (SVs) of 55 bacterial species in the gut microbiomes of 1,437 individuals from two cohorts and performed a systematic association study with 39 plasma BA parameters. Both variations in SV-based continuous genetic makeup and discrete clusters showed correlations with BA metabolism. Metagenome-wide association analysis identified 809 replicable associations between bacterial SVs and BAs and SV regulators that mediate the effects of lifestyle factors on BA metabolism. This is the largest microbial genetic association analysis to demonstrate the impact of bacterial SVs on human BA composition, and it highlights the potential of targeting gut microbiota to regulate BA metabolism through lifestyle intervention.
胆汁酸（BAs）促进肠道脂肪吸收，并作为宿主-肠道微生物群相互作用中的重要信号分子。已经确定了微生物群落中的 BA 代谢途径，但肠道细菌高度可变的基因组如何与宿主 BA 代谢相互作用在很大程度上仍不清楚。我们对来自两个队列的 1437 个人的肠道微生物组中的 55 种细菌的 8282 个结构变异（SV）进行了表征，并对 39 个血浆 BA 参数进行了系统的关联研究。基于 SV 的连续遗传组成和离散簇的变化均与 BA 代谢相关。宏基因组关联分析鉴定了 809 个可复制的细菌 SV 和 BAs 之间的关联，以及调节生活方式因素对 BA 代谢影响的 SV 调节剂。这是最大的微生物遗传关联分析，证明了细菌 SV 对人类 BA 组成的影响，并强调了通过生活方式干预靶向肠道微生物群来调节 BA 代谢的潜力。
