*3.3.2 Dyshomeostasis due to dysbiosis*

*Parasitology and Microbiology Research*

cardiovascular diseases.

psoriasis [92, 93].

**3.3 Microbiota and integumentary system**

*3.3.1 Role of the gut microbiota in skin homeostasis*

In some earlier research studies, a significantly low synthetic capacity to produce TMA and TMAO from dietary L-carnitine as well as a subsequent lower plasma levels of TMAO have been observed in vegetarians as compared to omnivores. Likewise, significant variations in microbial communities have also been reported in vegetarians as compared to omnivores [88, 89] suggesting that chronic dietary exposure, i.e., omnivores vs. vegetarians, leads to shift of microbial composition with a selective advantage for bacterial species having potential for increased TMA production, and, thus, may interfere with treatment of atherosclerotic

The gastrointestinal (GI) system and skin are highly vascularized and densely innervated organs with crucial neuroendocrine and immune roles which are uniquely related to the normal function of skin [90]. Evidence of bidirectional and intimate connection between the gut and skin health as well as a close link between GI health to skin allostasis and homeostasis has been established [91]. GI disturbances resulted often in cutaneous manifestations and the GI system, especially the gut microbiota, appears to participate in the pathophysiology

The mechanism by which GI flora exert their effect on skin homeostasis is still unknown; however it is postulated that probably such effect may be related to the modulatory influence of gut commensals on the systemic immunity [94]. Certain gut microbiota and their metabolites, i.e., polysaccharide A, retinoic acid from *Faecalibacterium prausnitzii*, *Bacteroides fragilis,* and bacteria belonging to the *Clostridium* cluster IV and XI potentiate the accumulation of the lymphocytes and regulatory T cells which assist in the anti-inflammatory responses [90]. In addition to this immunomodulatory effect there is recent evidence that the intestinal microbiota may influence cutaneous pathology, physiology and more directly the modification of the immune response by the

In cases of disturbance in intestinal barriers, it was found that intestinal bacteria and their metabolites may have the propensity to accumulate in the skin and have also access to the bloodstream which ultimately disrupts skin homeostasis. In fact, DNA of intestinal microbes has been separated from the plasma of psoriatic patients, thus showing a direct connection between the gut microbiota and skin homeostasis [90]. The short chain fatty acids (SCFAs), i.e., acetate, butyrate and propionate resulting from the fermentation of the fibers in GIT are believed to play an important role in the maintenance of certain skin microbiota which consequently affect cutaneous immune defense system. For example, propionic acid has an antimicrobial effect against the most common communityacquired methicillin-resistant *Staphylococcus aureus* (MRSA). Previous literature also demonstrates that SCFAs in skin play an important role in affecting the predominant residence of bacteria on normal human skin. It has been found that *P. acnes* and *S. epidermidis* have higher ability to tolerate the propionic acid than other pathogens. Thus, *P. acnes* and *S. epidermis* fermentation may have a low risk of disrupting the balance of skin microbiome. Altogether, these findings may provide supportive evidence for a functional interactive mechanistic approach

of many inflammatory diseases, i.e., acne, atopic dermatitis and

metastasis of gut microbiome and their metabolic activity [95].

**182**

between the skin and gut [96].

Intestinal dysbiosis may have the negative potential to affect the skin function since gut microbial flora has a huge potential to produce molecules, both harmful and beneficial, that could then reach the circulation and influence skin. Metabolic products of aromatic amino acids, i.e., *p*-cresol and free-phenols are considered biomarkers of a disturbed gut environment as their production is due to pathogenic bacteria such as *Clostridium difficile*. These metabolites may preferentially accumulate in the skin, enter the circulation blood and disrupt the epidermal differentiation and integrity of the skin barrier [90]. Indeed, high level of *p*-cresol and free-phenols is associated with impaired keratinization and decreased skin hydration [97]. Also, the intestinal dysbiosis is responsible for the increased permeability of epithelium which ultimately modulate the immune response by disrupting their balance with immunosuppressive regulatory T cells and thereby triggers the activation of T cells effectors. It has also been observed that epithelial permeability is further enhanced by the pro-inflammatory cytokines and result in chronic systemic inflammation [98].
