Ampicillin drives gut dysbiosis and progressive depigmentation in a mouse model of vitiligo

As gut bacteria influence systemic immunity, we questioned whether vitiligo development is affected by microbial colonization of the developing gut. In arthritis-prone mice, neomycin but not ampicillin favors colonization of gut bacteria that activate Th17, enhancing antibody-mediated ankle thickening. Vitiligo, instead involves CD8 T cell-mediated depigmentation, therefor the same treatments might affect depigmentation differently. Pregnant vitiligo-prone FH mice received either ampicillin or neomycin-enriched drinking water, or normal water ad libitum. Depigmentation was measured bimonthly in treated pups. Total DNA quantities of fecal pellets and microbiome composition of the gut and skin were evaluated, accompanied by staining for T cell populations in the skin and ileum. Cytokine arrays were performed on gut tissue and serum, and peptide responses were assessed among splenocytes. Surprisingly, ampicillin (N=10), but not neomycin (N=8) or control treatment (N=10), resulted in 2.6-fold increased depigmentation of vitiligo-prone animals in 30 weeks. 16SrRNA sequencing revealed markedly decreased biodiversity in the gut, not the skin of antibiotic treatment groups, with dominant colonization by Pseudomonas in ampicillin treated, and Bacteroides in neomycin-treated mice. T-cell abundance was reduced in the gut and skin of ampicillin-treated mice. A trend towards reduced depigmentation after neomycin treatment was accompanied by increased cutaneous Treg abundance, while splenocytes displayed enhanced responses to cognate peptide. Meanwhile T cells from ampicillin treated mice were more refractory. High IL-1a levels suggest gut inflammation after ampicillin, accompanied by type 1 and type 17 cytokines in the serum. This prompts studies of the causative effects of individual microbes, and solidifies genetic predisposition as a disease determinant.