Co-housing Alters Gut Microbiota and Disease Severity in Experimental Pemphigoid Disease

Pemphigoid diseases (PD) are autoimmune blistering disorders in which alterations of the skin and gut microbiota have been reported, yet how microbial variation relates to disease severity remains unclear. Using a bullous pemphigoid-like mouse model, we compared genetically identical C57BL/6J mice from two breeding facilities that differed in their baseline microbiota. Mice from Charles River developed markedly milder disease than in-house-bred animals. Co-housing partially homogenized their gut microbiota, shifting in-house mice asymmetrically toward the Charles River community, coinciding with reduced disease severity in co-housed in-house mice. The skin microbiota showed more modest and less consistent shifts, potentially reflecting its lower biomass and higher technical noise. Lower gut microbial diversity and enrichment of pro-inflammatory taxa like Turicimonas muris and Muribaculum intestinale were linked to more severe disease, whereas taxa such as Lactobacillus intestinalis and Parabacteroides distasonis correlated with protection. A gut taxon belonging to Scatocola was identified as a candidate negative predictor of disease severity in correlation and machine-learning analyses. Together, these findings support an association between natural variation in the gut microbiota and autoimmune skin inflammation and identify candidate microbial taxa that warrant further functional validation.