Microbiota network modules-derived tryptophan metabolites improve cognition via microglial AhR/Sirpα signaling

ABSTRACT:

Gut microbiota dysbiosis has emerged as one of the hallmarks of aging, highlighting the need to identify microbial network modules as new biomarkers rooted in microbiota interactions and develop targeted nutritional interventions. The current research, integrating data from Alzheimer's disease (AD) patient cohorts, meta-analysis and animal experiments, identified 4 core bacterial genera modules associated with aging and cognition. The combination of Bacteroides thetaiotaomicron, Lachnospiraceae bacterium and Roseburia intestinalis was positively correlated with neurofunction and significantly improved cognitive performance in LPS-induced and AD mice. Metabolomic profiling revealed disrupted tryptophan metabolism in aging mice, which was restored upon intervention with the core bacterial strains. Mechanistically, tryptophan metabolites activated the aryl hydrocarbon receptor (AhR) in the hippocampus, modulating microglial phagocytosis via Sirpα and Trem2 signaling. Moreover, sesaminol enhanced cognitive function by modulating specific modules. These findings elucidated the role of the microbiota-tryptophan metabolites-microglia axis in anti-aging and provided new directions for microbiota-targeted interventions.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS12508 | MetaboLights | 2026-08-08

REPOSITORIES: MetaboLights