## 6 Therapies Targeting Gut Microbiota's Composition
#### Therapies Targeting Microbiota Composition in Atopic Dermatitis
Nutritional products containing prebiotics and/or probiotics yield favorable effects on the skin by regulating the immune system and offering therapeutic advantages for conditions such as atopic diseases [153]. Probiotics modulate the overall microbiome and the immune system, potentially responsible for allergic reactions and the severity of atopic dermatitis. They inhibit the Th2-cell-mediated response, reducing pro-inflammatory cytokines, improving the Th1/Th2 ratio, decreasing INF-\(\gamma\), stimulating phagocytosis, and increasing IgA levels [152]. Probiotics also exert their effects on the surface of epithelial cells by influencing the strength of the epithelial cell barrier and controlling the function, protein expression, and mucin secretion [157]. Probiotic bacteria generate substantial quantities of short-chain fatty acids by fermenting dietary fiber, and these acids exhibit strong anti-inflammatory properties and support the health of epithelial tissues. Probiotics can also regulate both innate and adaptive immune responses [151]. The effectiveness relies on the assumption that these positive outcomes take place throughout the body, as probiotics produce targeted effects in the intestinal environment, as well as on epithelial and immune cells, which may possess anti-allergic properties [153]. The administration of _Lactobacillus_ and other probiotics in pregnant women has been shown to halve the risk of developing AD in children at 2 years of age [158]. Other recent study describes that administering probiotics during pregnancy and early childhood seems to have a positive effect in preventing the development of atopic dermatitis (AD) in infants [159]. However, the effectiveness of probiotics as a treatment is still unclear, needing further studies. Improving nutritional status, nutrient digestion, specific and nonspecific immune responses, and beneficial effects on the gastrointestinal tract and skin are arguments to support the use of prebiotics and probiotics in patients with atopic dermatitis (AD). However, there is still insufficient data in the literature to answer questions about the optimal dosage, the ideal timing to initiate treatment, and the necessary duration to demonstrate beneficial effects [152]. A direct consequence of improving nutritional status is the increase in short-chain fatty acids (SCFAs), which are a group of organic compounds that consist of fewer than six carbon atoms. They are primarily produced during the fermentation of dietary fiber by beneficial bacteria in the gut, particularly in the colon. Three of the most-common SCFAs are acetate (C2), propionate (C3), and butyrate (C4). These compounds play various essential roles in the body, including their notable anti-inflammatory effects, which can be particularly relevant in the context of atopic dermatitis, particularly for the following reasons: (i) Regulation of immune cells: SCFAs have been shown to modulate the function of immune cells, such as T cells and regulatory T cells (Tregs). Tregs play a crucial role in dampening excessive immune responses and inflammation. SCFAs can promote the development and activity of Tregs, thereby helping to suppress inflammation. (ii) Inhibition of pro-inflammatory cytokines: SCFAs can inhibit the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Elevated levels of these cytokines are often observed in inflammatory skin conditions such as atopic dermatitis, and their reduction can help alleviate inflammation. (iii) Barrier function improvement: Atopic dermatitis is characterized by a compromised skin barrier, which allows allergens and irritants to penetrate the skin more easily, leading to inflammation. SCFAs can enhance the integrity of the skin barrier by promoting the production of skin proteins such as filaggrin and involucrin, which play crucial roles in maintaining skin barrier function. (iv) Anti-microbial effects: SCFAs possess antimicrobial properties that can help regulate the skin microbiome.