Akkermansia muciniphila ameliorates imiquimod-induced skin thickening, colitis, and gut microbiota alterations: A metagenome association study

Summary: Abstract Body: A decreased abundance of fecal Akkermansia muciniphila (Akk) has been observed in patients with psoriasis and psoriatic arthritis. The potential beneficial effect of Akk in managing psoriasis has been proposed. We aimed to examine the impact of Akk on skin and systemic inflammation, intestinal barrier integrity, and gut microbiota profiles in psoriasis. We conducted a metagenomic association study of the Akk in the imiquimod (IMQ)-mice using whole-genome shotgun sequencing. A dextran sodium sulfate (DSS)- induced colitis experiment and intestinal permeability test were also performed. The association among Akk supplements, skin thickness, circulating inflammatory profiles, fecal microbiota alterations, intestinal epithelium inflammation, and barrier integrity was investigated. The microbiome study was performed using pipelines of phylogenetic analysis, functional gene analysis, and pathway analysis. In IMQ-treated mice, there were increases in skin thickness, splenic weight, and unique fecal microbial profiles compared to controls. Akk supplement ameliorated the IMQ-induced skin thickening, weight loss, spleen weight gain, serum IL-17A and TNF-α levels, and DSS-induced colitis. Akk supplement was associated with a greater fecal microbial diversity and an alteration in the fecal microbiota composition, with the increased prevalence of Muribaculaceae, Bifidobacterium pseudolongum, Desulfovirionaceae, Erysipelotrichaceae, and Alistipes ihumi, which have been involved in Gamma-Aminobutyric Acid (GABA) shunt, cholinergic synapse, cell cycle, and Mitogen-Activated Protein Kinase (MAPK) pathways. Akk may mitigate IMQ-induced skin thickening and DSS-induced colitis associated with reduced IL-17A levels. Akk supplement alters fecal microbiota and metabolism pathways in IMQ-treated mice. Yi-Ju Chen¹, Hsiu J. Ho², Yu-Feng Chen², Chun-Ying Wu² 1. Dermatology, Taichung Veterans General Hospital, Taichung, Taichung City, Taiwan. 2. National Yang Ming Chiao Tung University, Taipei, Taiwan Province, Taiwan. Innate Immunity, Microbiology, and Microbiome