Exploring the therapeutic potential of <i>Bifidobacterium longum subsp. longum</i> CCFM1029 in Parkinson's disease: Insights from behavioral, neurophysiological, gut microbiota, and microbial metabolites analysis

Abstract The pathogenesis of Parkinson's disease (PD) is closely related to the gut microbiota, and microecological therapies based on gut probiotics have received widespread attention, among which Bifidobacterium has been demonstrated to have a potential neuroprotective effect, but specific mechanisms have been lacking in the investigation. Here, we show that Bifidobacterium longum subsp. longum CCFM1029 significantly inhibited LPS‐induced inflammatory responses in microglia and alleviated 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced motor dysfunction, dopaminergic neuronal damage, and neuroinflammation in PD mice. Subsequently, the mechanism of action of CCFM1029 in PD was systematically elucidated by the neurochemical and biochemical analysis in PD mice, together with microbiomic and metabolomic analysis. It was found that CCFM1029 intervention restores dysbiosis in the gut microbiota linked to PD and reverses alterations in microbial metabolites. We established the interactions among the gut microbiota, metabolites, and brain by integrating behavioral and neurophysiological data with changes in the composition of the gut microbiota and metabolomic characteristics. We found that CCFM1029 intervention increases levels of the beneficial gut microbial metabolites indole‐3‐acrylic acid and short‐chain fatty acid (acetic and butyric acid) and decreases levels of the neuroinflammation‐associated metabolite N‐acetylhistamine. To summarize, our findings suggest CCFM1029 as a novel dietary supplement can prevent and mitigate the progression of PD through the microbiota‐gut‐brain axis.