Immunological and genetic features of pathogenetic association between psoriasis and colonic dysbiosis
Psoriasis is a multifactorial systemic immune-associated disease. It is assumed that colonic dysbiosis may contribute to its development. In this review we provide the data on colonic dysbiosis in induction and progression of psoriatic inflammation assessing a role for bacterial species: Akkermansia muciniphila, Faecalibacterium prausnitzii and Escherichia coli. On one hand, these bacterial species indicate at state of dysbiotic bacterial communities, whereas on the other hand, they are functionally associated with triggering a chain of events inducing impaired intestinal barrier transforming into chronic inflammation in the colonic mucosa and systemic inflammation. Such a scenario leads to the altered systemic reactivity of innate and adaptive immune cells, impaired function of regulatory immune cells resulting in expansion of the autoreactive skin T-cells and induction of psoriatic inflammation due to molecular mimicry between persistent Streptococcus pyogenes and cutaneous antigens. The psoriatic process is envisioned as a comorbidity with inflammatory bowel diseases. Since dysbiotic changes in psoriasis and inflammatory bowel diseases (e.g. Crohn's disease) display similar features, these diseases might potentially proceed via a similar pathogenetic chain resulting from dysbiotic changes in intestinal microbiota towards impaired intestinal barrier, chronic systemic inflammation and altered anti-inflammatory immune arm. Therefore, the data on pathogenetic pathways of the diseases comorbid with psoriasis are able to uncover yet-unknown pathogenetic components for the latter. Psoriasis as a genetically-determined disease is currently believed to be associated with single nucleotide polymorphisms (SNP) in more than four hundred genes. A role for diverse SNPs in candidate genes involved in psoriasis pathogenetic chain in antigen processing and presentation, migration of immune cells, pro-inflammatory cytokine ligation and production is discussed. Crohn's disease is associated with single nucleotide polymorphisms of the genes encoding intestinal barrier proteins potentially underlying its functional deficiency. In connection with comorbidity and similarity between microbiota-associated pathogenetic psoriasis chain and inflammatory bowel diseases, it is possible to assume that such SNPs accounting for genetic defects in the intestinal barrier are manifested as dysbiotic changes in colonic bacterial community and contribute to progression not only of inflammatory bowel diseases, but psoriasis as well.