Department of Microbiome Science, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Department of Microbiome Science, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
Cell Host Microbe. 2019 Apr 10;25(4):553-564.e7. doi: 10.1016/j.chom.2019.03.001.
Host genetic variation influences microbiome composition. While studies have focused on associations between the gut microbiome and specific alleles, gene copy number (CN) also varies. We relate microbiome diversity to CN variation of the AMY1 locus, which encodes salivary amylase, facilitating starch digestion. After imputing AMY1-CN for ∼1,000 subjects, we identified taxa differentiating fecal microbiomes of high and low AMY1-CN hosts. In a month-long diet intervention study, we show that diet standardization drove gut microbiome convergence, and AMY1-CN correlated with oral and gut microbiome composition and function. The microbiomes of low-AMY1-CN subjects had enhanced capacity to break down complex carbohydrates. High-AMY1-CN subjects had higher levels of salivary Porphyromonas; their gut microbiota had increased abundance of resistant starch-degrading microbes, produced higher levels of short-chain fatty acids, and drove higher adiposity when transferred to germ-free mice. This study establishes AMY1-CN as a genetic factor associated with microbiome composition and function.
宿主遗传变异会影响微生物组的组成。虽然已有研究集中于肠道微生物组与特定等位基因之间的关联，但基因拷贝数 (CN) 也存在差异。我们将微生物组多样性与编码唾液淀粉酶的 AMY1 基因座的 CN 变异相关联，该酶有助于淀粉消化。在对约 1000 名受试者进行 AMY1-CN 推断后，我们鉴定出区分高和低 AMY1-CN 宿主粪便微生物组的分类群。在为期一个月的饮食干预研究中，我们表明饮食标准化驱动了肠道微生物组的趋同，而 AMY1-CN 与口腔和肠道微生物组的组成和功能相关。低 AMY1-CN 受试者的微生物组具有更强的分解复杂碳水化合物的能力。高 AMY1-CN 受试者唾液中普氏菌水平更高；他们的肠道微生物群中具有更高含量的抗性淀粉降解微生物，产生更高水平的短链脂肪酸，并在转移到无菌小鼠时导致更高的肥胖程度。本研究确立 AMY1-CN 为与微生物组组成和功能相关的遗传因素。
