Lychee Fermented by Mixed Probiotic Strains Alleviates D-Galactose-Induced Skeletal Muscle and Intestinal Aging in Mice

Aging-associated skeletal muscle and intestinal dysfunction is largely driven by chronic inflammation, oxidative stress, and microbiota imbalance. This study investigated the protective effects of a lychee fermentate (LF) in a D-galactose-induced aging mouse model. LF was prepared using a mixed microbial fermentation approach with <i>Lactiplantibacillus plantarum</i>, <i>Lacticaseibacillus casei</i>, <i>Saccharomyces cerevisiae</i>, and <i>Acetobacter pasteurianus SP021</i>. LF administration significantly improved muscle strength and endurance and restored muscle fiber morphology. Meanwhile, LF alleviated colonic transit impairment and downregulated senescence markers p16 and p21. H&E and AB-PAS staining showed that intervention with LF ameliorated the colonic tissue damage, preserved goblet cell populations and promoted MUC2-mediated mucus secretion, which was further confirmed by the upregulation of intestinal barrier-related proteins MUC2, ZO-1, Claudin-1, and Occludin through immunofluorescence analysis. In addition, LF reduced colonic inflammation by suppressing IL-1β, IL-6, TNF-α, CXCL1, and MCP1 expression, and mitigated oxidative stress by lowering malondialdehyde levels to 24.65 ± 3.84 nmol/mL while enhancing glutathione peroxidase and superoxide dismutase activities. Moreover, the LF restored intestinal health by modulating microbiota homeostasis, such as adjusting the Firmicutes/Bacteroidetes ratio and increasing the abundance of beneficial bacteria like Clostridia_UCG-014 and Alistipes. Metabolomic profiling indicated that the enhanced bioactivity of the LF was primarily attributed to the enrichment of phenolic acids, flavonoids and their derivatives postfermentation, including ethyl caffeate, gallic acid, kaempferol and isorhamnetin. In summary, these findings provided new insights into the potential application of LF as a functional food for mitigating skeletal muscle and intestinal aging.