Antibiotics in neonatal life increase murine susceptibility to experimental psoriasis

Abstract

Psoriasis is an inflammatory skin disease affecting ∼2% of the world's population, but the aetiology remains incompletely understood. Recently, microbiota have been shown to differentially regulate the development of autoimmune diseases, but their influence on psoriasis is incompletely understood. We show here that adult mice treated with antibiotics that target Gram-negative and Gram-positive bacteria develop ameliorated psoriasiform dermatitis induced by imiquimod, with decreased pro-inflammatory IL-17- and IL-22-producing T cells. Surprisingly, mice treated neonatally with these antibiotics develop exacerbated psoriasis induced by imiquimod or recombinant IL-23 injection when challenged as adults, with increased IL-22-producing γδ+ T cells. 16S rRNA gene compositional analysis reveals that neonatal antibiotic-treatment dysregulates gut and skin microbiota in adults, which is associated with increased susceptibility to experimental psoriasis. This link between neonatal antibiotic-mediated imbalance in microbiota and development of experimental psoriasis provides precedence for further investigation of its specific aetiology as it relates to human psoriasis.

Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity

“…Here, we demonstrate that the microbiome also plays a key role in the regulation of cytokine production. This conclusion is supported by studies showing that perturbations such as antibiotic treatment greatly impact development of autoimmune diseases such as psoriasis (Zanvit et al, 2015) and are associated with allergic asthma susceptibility (Russell et al, 2012). In addition, the use of antibiotics is associated with a more pronounced dysbiosis in children with Crohn’s disease, implicating perturbations of the gut microbiota in disease (Gevers et al, 2014).…”

How colonization by microbiota in early life shapes the immune system

“…Further, the accumulation of activated T reg cells during this early-life period appears to be specific to the skin and is not observed in the intestinal lamina propria. Antibiotic treatment in neonatal mice can induce long-term modification of microbial composition of the skin and susceptibility to psoriasis development in adulthood, which is associated with increased IL-22–producing γδ T cells (71). Regulation of thymically derived and induced T reg cells by microbiota during early life therefore appears to be tissue-specific, suggesting that even the same cell type (such as T reg ) is under the influence of distinct organ-specific mechanisms.…”

The Snowballing Literature on Imiquimod-Induced Skin Inflammation in Mice: A Critical Appraisal

“…Grooming and scratching behaviors can also result in significant excoriation and thickening of the epidermis, as it does in humans. Further, how oral ingestion of IMQ alters the gut microbiome and the inflammatory skin phenotype of this particular mouse model is largely unknown (Zanvit et al, 2015). Therefore, restraint must be exercised before drawing definitive conclusions about the cause of systemic inflammation (e.g., splenomegaly and lymphadenopathy) or phenotypic differences observed in this model.…”