Young gut microbiota transplantation improves the metabolic health of old mice.

Abstract

The gut microbiota evolves over a lifetime and significantly impacts the aging process. Targeting the gut microbiota represents a novel avenue to delay aging and aging-related physical and mental decline. However, the underlying mechanism by which the microbiota modulates the aging process, particularly age-related physical and behavioral changes is not completely understood. We conducted fecal microbiota transplantation (FMT) from young or old male donor mice to the old male recipients. Old recipients with young microbiota had a higher alpha diversity than the old recipients with old microbiota. Compared to FMT with old microbiota, FMT with young microbiota reduced body weight and prevented fat accumulation in the old recipients. FMT with young microbiota also lowered frailty, increased grip strength, and alleviated depression and anxiety-like behavior in the old recipients. Consistent with observed physical changes, untargeted metabolomic analysis of serum and stools revealed that FMT with young microbiota lowered age-related long-chain fatty acid levels and increased amino acid levels in the old recipients. Bulk RNAseq analysis of the amygdala of the brain showed that FMT with young microbiota downregulated inflammatory pathways and upregulated oxidative phosphorylation in the old recipients. Our results demonstrate that FMT with young microbiota has substantial positive influences on age-related body composition, frailty, and psychological behaviors. These effects are associated with changes in host lipid and amino acid metabolism in the periphery and transcriptional regulation of neuroinflammation and energy utilization in the brain.