| Summary: | White button mushroom polysaccharide (WMP) has various health-promoting functions. However, whether these functions are mediated by gut microbiota has not been well explored. Therefore, this study evaluated the anti-aging capacity of WMP and its effects on the diversity and composition of gut microbiota in D-galactose-induced aging mice. WMP significantly improved locomotor activity and the spatial and recognition memory of the aging mice. It also alleviated oxidative stress and decreased the pro-inflammatory cytokine levels in the brain. Moreover, WMP increased α-diversity, the short-chain fatty acid (SCFA) level and the abundance of beneficial genera, such as <i>Bacteroides</i> and <i>Parabacteroides</i>. Moreover, its effect on <i>Bacteroides</i> at the species level was further determined, and the enrichments of <i>B. acidifaciens, B. sartorii</i> and <i>B. stercorirosoris</i> were found. A PICRUSt analysis revealed that WMP had a greater impact on the metabolism of carbon, fatty acid and amino acid, as well as the MAPK and PPAR signaling pathway. In addition, there was a strong correlation between the behavioral improvements and changes in SCFA levels and the abundance of <i>Bacteroides</i>, <i>Parabacteroides, Mucispirillum</i> and <i>Desulfovibrio</i> and <i>Helicobacter</i>. Therefore, WMP might be suitable as a functional foods to prevent or delay aging via the directed enrichment of specific species in <i>Bacteroides</i>.
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