Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
School of BioSciences, The University of Melbourne, Melbourne, Victoria, Australia.
Nat Genet. 2022 Feb;54(2):134-142. doi: 10.1038/s41588-021-00991-z. Epub 2022 Feb 3.
Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.
人类遗传变异通过环境和宿主因素的复杂组合影响肠道微生物群。在这里，我们在一个包含 5959 名个体的大型基于人群的队列中对与微生物丰度相关的遗传变异进行了特征描述，这些个体具有匹配的肠道微生物宏基因组、饮食和健康记录（现患和随访）。我们鉴定出了 567 个独立的 SNP-分类群关联。位于 LCT 基因座的变异与双歧杆菌和其他分类群相关，但它们因乳制品摄入而异。此外，Faecalicatena lactaris 的水平与 ABO 相关，并提示在肠道中优先利用分泌的血液抗原作为能量来源。肠球菌粪肠球菌的水平与 MED13L 基因座的变异相关，该基因座已与结直肠癌相关。孟德尔随机化分析表明，Morganella 对重度抑郁症有潜在的因果影响，这与观察性疾病发病分析一致。总体而言，我们鉴定并描述了宿主-微生物群相互作用的复杂性质及其与疾病的关联。
