Accumulating data suggest that remodeling aged gut microbiota improves aging-related imbalance in intestinal homeostasis. However, evidence in favor of the beneficial effect of remodeling gut microbiota on intestinal stress and immune responses during aging is scarce. The current study revealed that old mice presented impaired gut barrier integrity. Transcriptome sequencing coupled with bioinformatics analysis revealed that aging altered gene expression profiles of the colon and mesenteric lymph nodes, which are involved mainly in stress and immune responses, respectively. Notably, gut microbiota was closely related to the differentially expressed genes. Microbiota depletion in old mice ameliorated gut barrier integrity and partially reversed the inflammatory factors upregulated in aging mice. Furthermore, fecal microbiota transplantation from young mice to old mice resulted in a significant improvement in intestinal barrier integrity and immune homeostasis. These findings highlight the potential of microbiota-targeted interventions on aging-related physiological processes and call for further investigation.

© 2025. The Author(s).