The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals. We observed substantial daily fluctuations, with intra-individual variations in gut microbiome and metabolism associated with changes in stool moisture and faecal pH, and inter-individual variations accounted for by whole-gut and segmental transit times and pH. Metabolites derived from microbial carbohydrate fermentation correlated negatively with the gut passage time and pH, while proteolytic metabolites and breath methane showed a positive correlation. Finally, we identified associations between segmental transit time/pH and coffee-, diet-, host- and microbial-derived metabolites. Our work suggests that gut physiology and environment are key to understanding the individuality of the human gut microbial composition and metabolism.

人类肠道微生物组是高度个人化的。然而，肠道生理学和环境对肠道微生物组变化的贡献仍未得到充分研究。在这里，我们使用多组学进行了一项观察性试验，以连续 9 天分析 61 名健康成年人的微生物组组成和代谢。我们评估了肠道环境因素的日常变化，并使用无线运动胶囊在 50 个个体的子集中测量了全肠道和节段性肠道转运时间和 pH 值。我们观察到大量的每日波动，肠道微生物组和新陈代谢的个体内变化与粪便水分和粪便 pH 值的变化有关，而个个间差异则由整个肠道和节段的转运时间和 pH 值解释。微生物碳水化合物发酵衍生的代谢物与肠道通过时间和 pH 值呈负相关，而蛋白水解代谢物和呼吸甲烷呈正相关。最后，我们确定了节段性转运时间/pH 值与咖啡、饮食、宿主和微生物衍生代谢物之间的关联。我们的研究表明，肠道生理学和环境是了解人类肠道微生物组成和新陈代谢个体性的关键。