The human gastrointestinal tract represents one of the largest interfaces (250–400 m2) between the host, environmental factors, and antigens in the human body. The collection of bacteria, archaea, and eukarya colonizing the gastrointestinal tract is termed the ‘gut microbiota’. The ratio of human to bacterial cells is close to 1:1. As a result of the vast number of bacterial cells in the body, the host and the microorganisms inhabiting it are often referred to as a ‘superorganism’.
The microbiota offers many benefits to the host, through a range of physiological functions such as strengthening gut integrity or shaping the intestinal epithelium, harvesting energy, protecting against pathogens, and regulating host immunity. Many human and animal studies suggest that the intestinal microbiome’s influence extends beyond the gut, and contributes to the function, and dysfunction, of distant organ systems. The skin has a particularly complex connection with the gut.
The mechanisms by which intestinal microbiota exert their influence on skin homeostasis appear to be related to the modulatory effect of gut commensals on systemic immunity. Certain gut microbes and metabolites – retinoic acid, polysaccharide A from Bacteroides fragilis, Faecalibacterium prausnitzii, and bacteria belonging to Clostridium promote the accumulation of regulatory T cells, lymphocytes which facilitate anti-inflammatory responses. Segmented filamentous bacteria, alternatively, promote the accumulation of pro-inflammatory Th17 and Th1 cells. Th1 and Th17 cells may contribute to the pathogenesis and development of psoriasis.
Psoriasis is a non-contagious chronic inflammatory skin condition with a complex etiology that is relatively common in the general population, affecting men and women of all ages, regardless of ethnic origin, in all countries. Psoriasis is a T cell mediated disease involving Th17 cells secreting IL-17A and IL-22 which are proinflammatory cytokines that cause the proliferation of keratinocyte and activation of synoviocyte.
In addition, there is new evidence that the intestinal microbiome may impact cutaneous physiology, pathology, and immune response more directly, through the metastasis of gut microbiota and their metabolites to the skin. In cases of disturbed intestinal barriers, intestinal bacteria as well as intestinal microbiota metabolites have been reported to gain access to the bloodstream, accumulate in the skin, and disrupt skin homeostasis. DNA of intestinal bacteria has been successfully isolated from the plasma of psoriatic patients.
The metabolites of pathogenic gut bacteria can access the circulation, preferentially accumulate in the skin, and impair epidermal differentiation and skin barrier integrity. Indeed, high p-cresol serum levels are associated with reduced skin hydration and impaired keratinization. Intestinal dysbiosis results in increased epithelial permeability which then triggers the activation of effector T cells, disrupting their balance with immunosuppressive regulatory T cells. Pro-inflammatory cytokines further enhance epithelial permeability and set up a vicious cycle of chronic systemic inflammation. Skin barrier dysfunction and altered immune responses are primary players in the pathogenesis of atopic dermatitis. A compromised barrier secondary to environmental or genetic causes is typically the preceding event in atopic dermatitis development.
This intestinal microbial dysbiosis poses an interesting field of investigation and application. Pre- and probiotics aimed at the intestinal microbiome may be used for targeting skin health. It was reported that Probiotic-fed mice with Lactobacillus reuteri demonstrated shinier and thicker fur mediated through IL-10. Several human studies showed that the consumption of probiotics or live bacteria that are beneficial for the gastrointestinal system has the potential to prevent and manage various skin diseases, such as acne vulgaris, atopic dermatitis, and psoriasis. However, specific diets such as caloric restriction and low-fat diets have also been associated with an improved intestinal epithelial barrier or with cutaneous improvements, including wound healing, skin cancer, and even skin aging.
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