Introduction
The intestinal microbiome has emerged as a major regulator of metabolic health, inflammation and healthy aging. Dietary patterns strongly influence microbial diversity and metabolite production, with fiber-rich and plant-based diets generally promoting beneficial microbial ecosystems. The Dietary Index for Gut Microbiota (DI-GM) was developed to quantify the impact of habitual diet on gut microbial health and has previously been associated with favorable metabolic outcomes in selected disease populations.
Problem Statement
Although microbiota-supportive dietary patterns may influence longevity, the relationship between DI-GM and premature mortality in the general population has not previously been established. Furthermore, whether biological aging mediates the association between gut microbiota–oriented dietary patterns and survival outcomes remains unclear.
Summary
This large longitudinal NHANES-based cohort study evaluated more than 15,000 U.S. adults and demonstrated a strong inverse relationship between DI-GM scores and both premature and all-cause mortality. Each one-point increase in DI-GM was associated with approximately 9% lower premature mortality risk and 10% lower overall mortality risk after multivariable adjustment. Individuals with the highest DI-GM scores had substantially lower mortality risk compared with those with the poorest microbiota-associated dietary patterns. Kaplan–Meier analyses and smooth curve modeling further demonstrated a consistent linear relationship between higher DI-GM scores and improved survival outcomes across multiple demographic subgroups.
Importantly, the study identified biological aging as a major mediator of this protective association. Measures including PhenoAge acceleration, Klemera–Doubal biological age acceleration and homeostatic dysregulation partially explained the relationship between DI-GM and mortality. Among these, PhenoAge acceleration demonstrated the strongest mediating effect, accounting for more than one-third of the association with premature mortality. Higher DI-GM scores were consistently associated with lower biological age acceleration and reduced physiologic dysregulation.
Mechanistically, diets associated with higher DI-GM scores emphasized fiber-rich plant foods, whole grains, legumes, fermented dairy products, tea and coffee while minimizing processed meats, refined grains and high-fat dietary patterns. These dietary profiles likely promote short-chain fatty acid production, improved metabolic homeostasis and reduced chronic inflammation through favorable modulation of gut microbial diversity. Conversely, lower-quality diets may increase production of harmful microbial metabolites such as trimethylamine N-oxide, which has been linked to cardiovascular disease and mortality.
Overall, this study strengthens the concept that microbiota-oriented dietary patterns may influence longevity partly through modulation of biological aging processes. The findings support growing interest in gut microbiome–targeted nutritional strategies as scalable public health interventions for promoting healthy aging and reducing premature mortality.