The role of gut microbes in production of aromatic carboxaldehydes

Gut microbes play an important role in maintaining our health through the alteration of available nutrients and by the production of small molecules/metabolites. Indole-3-carboxaldehyde (I3A) is an aromatic carboxaldehyde (ArA) synthesized by gut microbes from the aromatic amino acid tryptophan, and has been mechanistically linked to antitumor activity, intestinal homeostasis, and metabolic syndrome. However, the capacity of gut microbes to produce other ArAs and their associations with host health remains largely unexplored due to a lack of methods for their detection and quantification. A stable isotope dilution mass spectrometry method for quantifying ArAs from all four aromatic amino acids (benzaldehyde (BA), 4-hydroxybenzaldehyde (4HBA), and 4-imidazolecarboxaldehyde (4IA) in addition to I3A) based on derivatization with 3-methoxyphenylhydrazine was developed and validated. Fecal levels of I3A and 4HBA were reduced in both human and mouse feces after a cocktail of nonabsorbable antibiotics depleted the gut microbiota, while the same treatment reduced BA in humans and 4IA in mice. Further, we identified multiple commensals with the capacity to produce selected ArAs in culture and showed that individuals with Crohn's disease, but not in those with ulcerative colitis, have lower fecal levels of I3A and 4HBA, relative to non-inflammatory bowel disease controls.