Microbial Metabolites in Allergic Diseases: Beyond Short-Chain Fatty Acids

The gut microbiota contributes to host homeostasis through the production of bioactive metabolites that regulate immune function. Some of these microbial metabolites, called short-chain fatty acids (SCFA), have been extensively associated with allergic diseases. However, this review aims to focus on other families of microbial metabolites that are also involved in regulating the immune and inflammatory responses. These include branched SCFA (BCFA), tryptophan and tyrosine (and their derivatives), secondary bile acids (BA), sphingolipids (SL), histamine, polyamines, and odd-chain fatty acid (OCFA)-containing metabolites.

In addition to the canonical SCFA, BCFA are also important regulators of innate and adaptive immunity. Specifically, they appear to participate in the mechanisms underlying allergic resolution and tolerance development. Furthermore, microbial derivatives of tryptophan, such as indole-3-acetic acid and indole-3-propionic acid, have been shown to regulate T helper 17 (Th17) and regulatory T cell populations, thereby reducing the allergic response. Products of the bacterial metabolism of other aromatic amino acids, such as tyrosine, are also associated with pro- and anti-inflammatory properties. Regarding secondary BA, isolithocholic acid has recently emerged as a key inhibitor of the Th17 response. Additionally, SL help maintain epithelial integrity and modulate the inflammatory response by regulating the levels of bioactive lipids, including ceramides and sphingosine-1-phosphate. Lastly, alterations in the bacterial metabolism of polyamines, including spermidine, and OCFA-containing metabolites, including lysophosphatidylcholines (LCP), have also been reported in allergic diseases. The microbiota metabolism modulates the immune response of its host and represents a potential target for the implementation of personalized therapeutic strategies in allergic patients.