Antibiotics Drive Microbial Imbalance and Vitiligo Development in Mice

Abstract

Vitiligo is impacted by environmental triggers. We studied the contribution of the microbiome in FH mice, in which depigmentation is mediated by tyrosinase-reactive T cells. The mice received oral antibiotics and were monitored for depigmentation. The microbiome was studied in fecal and skin samples using 16S rRNA analysis. The resulting T-cell distributions were evaluated. In untreated mice, pigment loss did not expand to the pelage, whereas mice in the ampicillin group were approximately 1/3 depigmented at 30 weeks. In contrast to models of autoimmunity that are less dependent on IFN-g, ampicillin but not neomycin treatment correlated with accelerated disease and reduced bacteria in the fecal pellets. Modified cytokine patterns in the tissue and serum suggest a response that transcends the gut. Ampicillin-induced depigmentation was accompanied by gut but not skin dysbiosis, and reduced T cell numbers in both sites. Neomycin induced a redistribution of gut T cells and an accumulation of skin regulatory T cells. This treatment spurred a Bacteroides-dominated population of fecal bacteria. Reduced diversity is prominent particularly after ampicillin treatment, when the gut is dominated by Pseudomonas species. In line with current concepts relating the microbiome and the immune system, we predict that dietary measures might promote skin health and delay vitiligo onset.

Host–microbiota interactions in immune-mediated diseases

“…Vitiligo is a T cell-mediated autoimmune disease that leads to loss of cutaneous melanocytes and subsequent depigmentation. In a mouse model of vitiligo, accelerated onset and expansion of depigmented skin and hair was observed in response to treatment with the oral antibiotic ampicillin, but not neomycin, suggesting that alteration of specific gut bacterial communities influences disease activity 101 . The antibiotics had little effect on the cutaneous microbiota but altered the gut microbiota and reduced T cell populations in the skin.…”

Mechanisms of skin autoimmunity: Cellular and soluble immune components of the skin

“…Systemic treatment with antibiotics altered the gut microbiome and with it the clinical course of vitiligo development in a murine model of vitiligo. 75 Similarly, high diversity of the skin microbiome of mice before disease induction protected mice from developing experimental epidermolysis bullosa acquisita. 76 An altered microbiome has also been described for blistering autoimmune diseases such as BP 77 or pemphigus.…”

Extrinsic Factors Shaping the Skin Microbiome

“…Dellacecca et al [ 61 ] studied the influence of oral ampicillin treatment on the microbiome of vitiligo skin. Upon antibiotic administration, treated animals were monitored for skin depigmentation.…”