Amuc_1100

Although diet has been regarded as a potential environmental risk factor for psoriasis, the precise contribution of specific dietary components, such as sugar, to its pathogenesis remains uncertain. Metformin, a primary medication for type II diabetes mellitus, has been documented to yield improvements in psoriasis. Earlier research indicates that the antihyperglycemic impact of metformin is associated with changes in gut microbiota. Nonetheless, the role of gut microbiota in the antipsoriatic effects of metformin remains unclear. In this study, we showed that 4 weeks of glucose intake exacerbated psoriasiform dermatitis (PsD) in mice, which resolved with oral metformin treatment. The exacerbation and resolution of PsD were mediated through effects on the gut microbiota. Supplementation with Akkermansia muciniphila, enriched by metformin, or Amuc_1100 improved PsD in glucose-fed mice but not in the control mice. Glucose intake resulted in reduced serum levels of indole-3-acetic acid, a microbial tryptophan metabolite, which were reversed by A muciniphila and Amuc_1100 treatment. Oral administration and intradermal injection of indole-3-acetic acid protected mice from glucose-promoted PsD with suppressed expression of antimicrobial peptides, specifically S100A8, in the epidermis. Collectively, increases of A muciniphila through metformin treatment led to reversal of glucose-promoted PsD in mice, possibly through production of the microbial tryptophan metabolite indole-3-acetic acid.

The gut microbiota-derived protein Amuc_1100, a key outer membrane component of Akkermansia muciniphila, has emerged as a groundbreaking therapeutic agent with unique structural and functional properties. Amuc_1100 exerts multifaceted immune-metabolic effects through novel mechanisms, including modulation of TLR2/4 and JAK/STAT pathways. This review highlights its unique multi-component structure that enables synergistic biological activity, and its pharmacological properties, which underlies its ability to enhance intestinal barrier integrity, restore microbiota balance, and suppress systemic inflammation. Crucially, Amuc_1100 demonstrates unprecedented therapeutic versatility across both intestinal disorders (e.g., inflammatory bowel disease, antibiotic-associated diarrhea) and extraintestinal conditions-notably improving neuropsychiatric symptoms via gut-serotonin axis regulation, combating cancer through CD8+ T cell activation, and mitigating cardiotoxicity via gut-heart immune crosstalk. Emerging innovations in targeted delivery systems, including gut-retentive nano-formulations and engineered probiotic vectors, further amplify its clinical potential. We critically evaluate recent advances distinguishing Amuc_1100's mechanisms from live bacterial interventions. By synthesizing evidence from preclinical models, this work positions Amuc_1100 as a prototype for next-generation microbiome-derived therapeutics, bridging microbial ecology with precision medicine.