Gut microbiota alterations associated with dietary inflammation and sarcopenia in humans and aged mice: insights from integrated metabolomic analysis.

Abstract

Objective: To investigate the association between the dietary inflammatory index (DII) and sarcopenia risk in older adults and identify cross-species microbial signatures linking dietary inflammatory burden with muscle phenotypes. Methods: A total of 1048 older adults were enrolled, and multivariable logistic regression models were applied to evaluate the association between the DII and sarcopenia risk. A sub-cohort of representative participants (n = 86) underwent fecal 16S rRNA gene sequencing. In parallel, a 10-week pro-inflammatory dietary intervention in naturally aged mice was conducted, followed by gut microbiome and skeletal muscle untargeted metabolomic profiling. Cross-species microbial signatures were identified by integrating human and mouse microbiome data. Results: Higher DII scores were associated with a greater prevalence of sarcopenia (OR = 1.305, 95% CI: 1.128-1.509). No significant difference in gut microbial α-diversity was observed between participants with and without sarcopenia, whereas β-diversity differed significantly between the two groups (p = 0.005). In aged mice, pro-inflammatory dietary intervention reduced grip strength and lean body mass and altered gut microbiota composition and skeletal muscle metabolic profiles. Group-by-time interaction effects for forelimb and all-limb grip strength remained significant after FDR correction (q < 0.05). Metabolomic changes were mainly enriched in lipid and amino acid metabolism pathways. Cross-species integration identified conserved microbial signatures, including the Family XIII AD3011 group, Akkermansia, and Fusobacterium. Conclusions: Higher dietary inflammatory burden is associated with increased sarcopenia risk and impaired muscle function in older adults. Gut microbiota alterations and skeletal muscle metabolic remodeling may contribute to this association. The identified cross-species microbial signatures provide potential targets for future mechanistic studies and nutritional interventions.