Study maps microbiome links between lifestyle and chronic disease

Researchers analyzed fecal shotgun metagenomic data from 6,803 adults in Japan’s 4D cohort, assessing 28 lifestyle factors alongside physician-confirmed general health and 15 chronic diseases. Analyses adjusted for age, sex, body mass index and microbiome-modulating medications. Fecal short-chain fatty acids and plasma cytokines were also measured in subsets of 1,713 and 1,740 participants, respectively.

The analysis identified two opposing microbiome-mediated patterns. A health-associated axis, enriched for microbial metabolism of dietary components, was linked to plant-based, soy and dairy intake. A disease-associated axis, enriched for oral-derived bacteria and pathobionts, was linked to refined carbohydrates and sedentary behavior. Alcohol was associated with both patterns. Fermentation starter-culture microorganisms did not show statistically significant mediation. The axes were supported by short-chain fatty acid and cytokine profiles, and microbiome-based prediction scores distinguished diseases in 13 external cohorts from five countries.

The findings provide a framework for studying links among lifestyle, microbiota and disease, but mediation analyses in an observational cohort cannot establish causality or demonstrate that microbiome-targeted interventions improve outcomes. The authors’ proposed use of microbiome-based assessment to guide lifestyle interventions remains a potential application, not a validated clinical strategy.