Akkermansia Muciniphila Ameliorates Imiquimod-Induced Skin Thickening, Colitis, and Gut Microbiota Alterations: A Metagenome Association Study.

A decreased abundance of fecal Akkermansia muciniphila (Akk) has been observed in patients with psoriasis and psoriatic arthritis. The potential beneficial effects of Akk in managing psoriasis have been proposed, yet results remain inconsistent and mechanisms unclear. Using imiquimod (IMQ)-treated C57BL/6 mice, we conducted a metagenomic association study of pasteurized Akk (pAkk) in the IMQ mice through whole-genome shotgun sequencing. We also performed a dextran sodium sulfate (DSS)-induced colitis experiment and an intestinal permeability test. The association among pAkk supplements, skin thickness, inflammatory profiles, fecal microbiota alterations, functional genetic predictions, intestinal epithelium inflammation, and barrier integrity was investigated. The study demonstrated that pAkk supplementation ameliorated IMQ-induced skin thickening, weight loss, spleen weight gain, serum IL-17A, TNF-α levels, and DSS-induced colitis. pAkk supplementation was linked to greater fecal microbial diversity and alterations in fecal microbiota composition, with increased prevalence of Muribaculaceae, Bifidobacterium pseudolongum, Desulfovirionaceae, Erysipelotrichaceae, and Alistipes ihumi, which have been implicated in the Gamma-Aminobutyric Acid (GABA) shunt, cholinergic synapse, cell cycle, and Mitogen-Activated Protein Kinase (MAPK) pathways. In conclusion, pAkk may mitigate IMQ-induced skin thickening and DSS-induced colitis, associated with reduced levels of TNF-α and IL-17A. pAkk supplementation alters fecal microbiota and metabolic pathways in IMQ-treated mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10753-025-02436-9.