AKKERMANSIA-ASSOCIATED METABOLIC REMODELING LINKS GUT MICROBIOTA CHANGES TO NEUROBEHAVIORAL RECOVERY FOLLOWING INVASIVE LASER ACUPUNCTURE

Parkinson’s disease (PD) is characterized by progressive neurodegeneration accompanied by neuroinflammation and gastrointestinal dysfunction, increasingly recognized to involve the gut–brain axis. Invasive laser acupuncture (ILA) has shown therapeutic potential in PD; however, the underlying microbiota- and metabolite-associated mechanisms remain unclear. Here, we investigated whether ILA improves neurobehavioral outcomes by remodeling gut microbiota and serum metabolomic profiles in a chronic MPTP-induced mouse model of PD.
ILA significantly ameliorated motor deficits and gastrointestinal dysmotility, while attenuating dopaminergic neuron loss and neuroinflammation in the substantia nigra and striatum. Gut histopathology and inflammatory signaling in the ileum were also markedly improved. Full-length 16S rRNA sequencing revealed that ILA selectively reshaped gut microbiota composition, with a prominent increase in Akkermansia muciniphila. Untargeted serum metabolomics further demonstrated that ILA induced a distinct metabolic profile, characterized by increased conjugated bile acids and acyl-carnitines, alongside reduced keto-type secondary bile acids.
To integrate microbiome, metabolome, and host phenotypes, we constructed an Akkermansia-aligned metabolic signature based on correlation-weighted metabolites. This composite signature showed strong associations with Akkermansia muciniphila abundance and neurobehavioral improvements, supporting a neurobehaviorally relevant gut–microbiota–metabolite axis. Triangulation analysis confirmed consistent relationships among Akkermansia abundance, the metabolic signature, and behavioral outcomes.
Collectively, these findings suggest that ILA promotes neurobehavioral recovery by remodeling gut microbiota and Akkermansia-associated metabolic pathways, highlighting a microbiota–metabolite–brain axis as a key mechanism underlying the therapeutic effects of ILA in Parkinsonian pathology.