Potential roles of gut microbial tryptophan metabolites in the complex pathogenesis of acne vulgaris

Abstract

Acne vulgaris is a chronic inflammatory skin disease in which the influence of gut microbiota has been implicated but without clarification of mechanisms. Gut microbiota may exert such an influence via metabolites, particularly those of tryptophan. End metabolites of tryptophan activate receptors, including aryl hydrocarbon, G protein-coupled, and pregnane X receptors to stabilize the immune microenvironment and intestinal mucosal homeostasis. Any impact on the pathogenesis of acne vulgaris remains unclear. The current review collates recent advances concerning potential roles of tryptophan metabolism in mediating skin inflammation, follicular sebaceous gland function and intestinal permeability, all of which influence the pathogenesis of acne vulgaris. The aim was to improve understanding of the pathogenesis of acne vulgaris and to expose therapeutic opportunities.

Keywords: acne vulgaris; aryl hydrocarbon receptors; gut microbiota (GM); metabolite; tryptophan.

FIGURE 1

Potential role of microbial Trp metabolites in the pathogenesis of acne vulgaris. Patients with acne vulgaris on a long-term Western diet may develop GM dysbiosis, which could result in a decrease in beneficial bacteria (e.g., Bifidobacterium, Lactobacillus), an essential metabolic link in the dietary Trp metabolism, and a reduction in potentially beneficial metabolites such as IAId, IAA, and ILA. In the local skin, Trp metabolites not only inhibit the production of pro-inflammatory factors such as IL-1β, IL-6, IL-8, and TNF-α by Mφ differentiating to M1 type through AhR but also promote the secretion of anti-inflammatory factors such as IL-10 and IL-22 by LC and ILC through AhR, and induce the differentiation of CD4+T cells to FoxP3+Treg and inhibit Th17 cells. On the other hand, Trp metabolites may also reduce sebum synthesis by inhibiting mTORC1, thus alleviating acne vulgaris. The “gut-skin” link may be caused by the disruption of the intestinal barrier caused by GM dysbiosis. Increased LPS in the gut may also enter the local skin through the peripheral circulation and aggravate the occurrence of acne vulgaris.