Short-chain Fatty Acids Ameliorate Imiquimod-induced Skin Thickening and IL-17 Levels and Alter Gut Microbiota in Mice: a Metagenomic Association Analysis

Short-chain fatty acids (SCFAs) have been proposed to have anti-inflammatory effects and improve immune homeostasis. We aimed to examine the effects of SCFAs on skin phenotype, systemic inflammation, and gut microbiota in mice with psoriasis-like inflammation. Imiquimod (IMQ)-treated C57BL/6 mice served as the study model. We conducted a metagenomic association study of IMQ-mice treated with SCFAs or anti-IL-17 antibody using whole-genome shotgun sequencing. The associations among SCFA supplements, skin thickness, circulating inflammatory profiles, and fecal microbiota profiles were investigated. The microbiome study was performed using pipelines for phylogenetic analysis, functional gene analysis, and pathway analysis. In IMQ-treated mice, there were increases in skin thickness and splenic weight, as well as unique fecal microbial profiles. SCFAs ameliorated IMQ-induced skin thickening, splenic weight gain, and serum IL-17F levels, with results that were comparable with those receiving anti-IL-17 treatment. IMQ-treated mice receiving SCFAs had greater microbial diversity than mice treated with IMQ alone. SCFAs and anti-IL17 treatment were associated with alteration of gut microbiota, with increased prevalences of Oscillospiraceae and Lachnopiraceae and decreased prevalences of Muribaculaceae and Bacteroides, which have been predicted to be associated with increased glycan degradation, phenylalanine metabolism, and xylene degradation. SCFAs may mitigate IMQ-induced skin thickening and IL-17F levels and alter fecal microbiota profiles in IMQ-treated mice.