Ecologically robust gut environment associated with personalized metabolic responses in a Japanese cohort

The gut microbiota produces numerous metabolites that affect host physiology. However, the effects of daily diet on human fecal metabolome profiles and their robustness are not well understood, and examinations of intra-individual stability over multiple time points are limited. Here, we investigated the robustness of the human intestinal environment through fecal metabolome and microbiome profiling in response to daily dietary fluctuations. We analyzed 176 fecal samples from 25 healthy Japanese individuals subjected to three dietary regimens, including heterogeneous and homogeneous diets. Fecal metabolome and microbiome profiles were unique to each individual. Further in-depth analyses of seven of these individuals showed that these profiles were stable despite daily dietary fluctuations in six individuals. In addition, random forest classification successfully predicted each subject’s identity based on their metabolome profile. The correlation analysis also revealed that the food-metabolite and food-microbiome relationships were highly personalized. The findings from this study suggest that individual diet prior to sample collection is unlikely to influence the fecal metabolome and microbiome data to an extent that is not representative of the individual’s “normal” condition, which may lower barriers to future research on the gut environment and its implications for host health.