Abstract: The present study focused on the association between Bifidobacterium bifidum and host aging, aiming to evaluate the role of B. bifidum CCFM1359 in mitigating D-galactose-induced aging of mice through behavioral experiments, immunological assays, gut microbiota characterization and metabolomic analysis. The results showed that the supplementation of B. bifidum CCFM1359 significantly ameliorated D-galactose-induced cognitive decline including learning and memory capacity in mice, increased the activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), and decreased the levels of malondialdehyde (MDA) and the pro-inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The 16S rRNA gene sequencing of the fecal bacterial community demonstrated that the mitigating effect of B. bifidum CCFM1359 on aging was associated with increased relative abundance of beneficial genera including Dubosiella and Faecalibaculum and decreased abundance of the pro-inflammatory genus Turicibacter. Fecal metabolomics revealed that CCFM1359 intervention increased the levels of anti-aging metabolites such as melatonin, taurine, and deoxycholic acid. Microbe-metabolite interaction network analysis revealed that differential genera such as Romboutsia were positively correlated with deoxycholic acid, while others such as Christensenellaceae_uncultured showed negative correlation with melatonin and deoxycholic acid. These results indicated that B. bifidum CCFM1359 effectively alleviated host aging through improved cognitive function, anti-inflammatory and antioxidant effects, and restoration of gut microbiota homeostasis and associated metabolic dysregulation.

Key words: aging, probiotic, gut microbiota, microbiota-associated metabolites, Bifidobacterium