Gut microbiome may reveal inflammation and future disease risk better than age

By Dr. Sanchari Sinha Dutta, Ph.D.Reviewed by Lauren HardakerSep 9 2026

Why do some young adults already show inflammatory patterns usually seen decades later? A large microbiome study traces striking differences in immune and metabolic health to distinct communities of gut bacteria.

Study: Gut microbiota composition outperforms chronological age in predicting systemic inflammation and incident disease risk. Image Credit: e-crow / Shutterstock

Human gut microbiota composition is more strongly associated with systemic inflammation and a range of physiological measures than chronological age, while specific microbiota profiles are also linked to future disease risk, according to a new study published in the journal Nature Communications.

Background

Inflammaging is chronic, low-grade inflammation that gradually develops throughout the body with aging. It is a common feature of various chronic diseases, such as cardiovascular disease, type 2 diabetes, and obesity.

Inflammaging, characterized by increased blood levels of a few biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6)-6, and tumor necrosis factor (TNF)-α, may be influenced by several factors, including lifestyle factors, metabolic factors, genetics, and gut microbiota composition.

The human gut microbiota has been proposed as a contributor to inflammaging, given its pivotal role in modulating metabolism and immune response. However, it largely remains unknown whether age itself, gut microbiota composition, or both play major roles in modulating inflammaging.

The current study aimed to address this gap in the literature by exploring how a person’s chronological age (actual age of a person) and gut microbiota composition relate to systemic inflammation and subsequent disease risk.

Using paired fecal and blood samples from 1,199 adults in a population-based cohort of 7,493 individuals, the researchers examined how age and gut microbiota composition are associated with 30 plasma cytokines and 19 biochemical and physiological measures relevant to the pathophysiology of age-related diseases.

Key findings

The correlation analysis indicated that age is associated with higher levels of most biochemical and physiological measures and with increased plasma levels of 40% of cytokines.

Regarding the relative contributions of age and gut microbiota composition to plasma cytokines and physiological measures, the analysis revealed that gut microbiota composition explained more variance than age for 97% of cytokines and 84% of physiological measures.

The assessment of predictive generalizability showed that gut microbiota composition provided robust and generalizable predictive power for most plasma cytokines and physiological measures. These patterns were also reproduced for available measures in the independent MetaCardis cohort.

Regarding the contribution of distinct gut microbial communities to systemic inflammation, the analysis revealed that individuals with the Bacteroides 2 enterotype have elevated levels of pro-inflammatory cytokines and adverse metabolic profiles as early as early adulthood. They displayed an inflammaging-like phenotype up to 37 years earlier than those carrying other enterotypes, such as Bacteroides 1 and Prevotella, based on modeled trajectories of several inflammatory and physiological markers.

Furthermore, the Bacteroides 2 enterotype was associated with an increased risk of future incident disease across multiple organ systems. The elevated inflammatory cytokine profile observed in individuals with Bacteroides 2 enterotype may partly explain their increased risk of disease development over a follow-up period of up to 9 years, with an average follow-up of 8 years.

In contrast to the Bacteroides 2 enterotype, the high-diversity Richness (R) enterotype, enriched in taxa including the Eubacterium siraeum group, Lachnotalea, Paludicola, and members of the Ruminococcaceae family, showed an association with reduced levels of early-onset inflammatory markers and reduced future disease risk.

Study significance

The study reveals that gut microbiota composition shows stronger associations with systemic inflammatory and physiological measures than chronological age does, while specific microbiota enterotypes are also associated with subsequent disease risk, supporting the view that age may not be the sole driver of inflammaging.

The stronger predictive power of gut microbiota composition for systemic inflammation and physiological measures likely reflects the capacity of its multidimensional profile to capture inter-individual differences in inflammatory tone beyond chronological age.

Notably, the study findings indicate that microbiota-associated inflammatory profiles may be detectable in the blood up to 9 years before subsequent hospital-associated diagnoses.

The study identified Bacteroides 2 enterotype as a specific microbiota structure that co-occurs with systemic inflammation and metabolic measures associated with increased disease risk. A high-diversity enterotype was also identified that exhibits lower systemic inflammation and reduced disease risk.

These findings are in accordance with previous studies linking high gut microbiota diversity to healthier aging. The healthier inflammatory profile associated with the high-diversity enterotype may reflect the metabolic capacity of some of its enriched taxa to produce short-chain fatty acids, microbial metabolites known to enhance intestinal barrier integrity and mitigate intestinal inflammation. These processes may help delay or prevent inflammation-driven acceleration of cellular senescence, thereby potentially reducing the risk of developing age-related diseases.

A higher prevalence of the high-diversity enterotype was observed among older participants, possibly because older individuals with lower systemic inflammation and reduced morbidity are more likely to participate in cohort studies. Such selective participation may lead to underrepresentation of less healthy individuals in the study population, a general limitation of population-based research. Residual confounding also cannot be excluded, particularly from dietary factors that may influence both gut microbiota composition and systemic inflammation.

Notably, the study reported that the relative abundance of bacterial taxa enriched in the Bacteroides 2 enterotype increased with age across all enterotypes. This finding indicates that individuals assigned to other enterotypes may still harbor B2-associated taxa, which may influence their systemic inflammation profiles. In other words, individuals harboring higher levels of inflammaging-linked gut bacterial taxa may be more likely to exhibit an inflammaging-like phenotype, independent of their assigned enterotype.

Taken together, these findings highlight robust associations between gut microbiota composition, systemic inflammation, host physiology, and subsequent disease risk across the adult lifespan, and underline the need for longitudinal and interventional studies to establish causality.