Crucial Role of Microbiota in Experimental Psoriasis Revealed by a Gnotobiotic Mouse Model

Abstract

Psoriatic patients have altered microbiota, both in the intestine and on the skin. It is not clear, however, whether this is a cause or consequence of the disease. In this study, using an experimental mouse model of psoriasis induced by imiquimod (IMQ), we show that oral treatment with a broad spectrum of antibiotics (MIX) or metronidazole (MET) alone mitigates the severity of skin inflammation through downregulation of Th17 immune response in conventional mice. Since some antibiotics, including MET, can influence immune system reactivity, we also evaluated the effect of MIX in the same model under germ-free (GF) conditions. GF mice treated with MET did not show milder signs of imiquimod-induced skin inflammation (IISI) which supports the conclusion that the therapeutic effect is mediated by changes in microbiota composition. Moreover, compared to controls, mice treated with MIX had a significantly higher abundance of the genus Lactobacillus in the intestine and on the skin. Mice treated with MET had a significantly higher abundance of the genera Bifidobacterium and Enterococcus both on the skin and in the intestine and of Parabacteroides distasonis in the intestine. Additionally, GF mice and mice monocolonized with either Lactobacillus plantarum or segmented filamentous bacteria (SFB) were more resistant to IISI than conventional mice. Interestingly, compared to GF mice, IMQ induced a higher degree of systemic Th17 activation in mice monocolonized with SFB but not with L. plantarum . The present findings provide evidence that intestinal and skin microbiota directly regulates IISI and emphasizes the importance of microbiota in the pathogenesis of psoriasis.

Gut Microbiome in Psoriasis: An Updated Review

“…Another proposed mechanism underlying the link between gut dysbiosis and skin changes implies the modulation of T cells differentiation and function with an imbalance between Th17 and T regulatory (Treg) cells. In experimental model of psoriasis, it has been shown that alterations in the intestinal microbiota may promote Th17-mediated skin inflammation [12,13]. In this context, the study by Yeh et al [19] provides very interesting results, showing significantly greater changes in the gut microbiome of patients with psoriasis treated with secukinumab (interleukin-17 inhibitor) compared to ustekinumab (inhibitor of interleukin-12 and -23).…”

“…Preclinical investigations provide evidence for the role of the gut microbiome in psoriasis pathogenesis. In mice with an experimental model of psoriasis induced by imiquimod, oral treatment with broad-spectrum antibiotic reduces the severity of skin inflammation through downregulation of Th17 immune response [ 12 , 13 ]. These results are supported by clinical observations based on a case series showing improvement in psoriatic skin lesions after antibiotic treatment [ 14 ], modulation of gut microbiota by probiotics [ 15 ] or fecal microbial transplantation [ 16 ].…”

Metagenomic analysis of gut microbiota in non-treated plaque psoriasis patients stratified by disease severity: development of a new Psoriasis-Microbiome Index

“…The adhesion of specific members of gut microbiome to intestinal epithelial cells is found to be essential for the induction of Th17 cells 20 – 22 . Mice exposed to antibiotics showed inhibition of psoriasis induction by a dysregulation of gut and skin microbiota 23 – 25 .…”

Pathogenesis of psoriasis in the “omic” era. Part III. Metabolic disorders, metabolomics, nutrigenomics in psoriasis in psoriasis

“…The increased intake of ω-3 PUFA, folic acid, vitamins A, D and E may play a significant role due to their antiinflammatory properties [130][131][132]. Moreover, diet may modify gut microbiota by regulating the activity of Th17 and Treg.…”

“…Moreover, diet may modify gut microbiota by regulating the activity of Th17 and Treg. The importance of the gut-skin axis in pathogenesis of psoriasis has been recently documented [131].…”