Gut Microbial-Derived Metabolomics of Asthma

Abstract

In this review, we discuss gut microbial-derived metabolites involved with the origins and pathophysiology of asthma, a chronic respiratory disease that is influenced by the microbiome. Although both gut and airway microbiomes may be important in asthma development, we focus here on the gut microbiome and metabolomic pathways involved in immune system ontogeny. Metabolite classes with existing evidence that microbial-derived products influence asthma risk include short chain fatty acids, polyunsaturated fatty acids and bile acids. While tryptophan metabolites and sphingolipids have known associations with asthma, additional research is needed to clarify the extent to which the microbiome contributes to the effects of these metabolites on asthma. These metabolite classes can influence immune function in one of two ways: (i) promoting growth or maturity of certain immune cell populations or (ii) influencing antigenic load by enhancing the number or species of specific bacteria. A more comprehensive understanding of how gut microbes and metabolites interact to modify asthma risk and morbidity will pave the way for targeted diagnostics and treatments.

Keywords: asthma; bile acids; metabolomics; microbiome; polyunsaturated fatty acids; short chain fatty acids; sphingolipids; tryptophan.

Figure 1

Schematic of mechanisms whereby polyunsaturated fatty acids may influence asthma pathophysiology. Pathways in which microbial metabolism is essential are highlighted by the microbe icon.

Figure 2

Schematic of mechanisms whereby tryptophan metabolic pathways influence asthma pathophysiology. As indicated by the microbe icon, microbial exposure induces interferon-γ production, and gut bacteria participate in metabolism of tryptophan to indole, tryptamine and other metabolites with activity at the aryl hydrocarbon receptor. Abbreviations: AHR = aryl hydrocarbon receptor; IDO = Indoleamine 2,3-dioxygenase-1.