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 the gut microbes from the aromatic amino acid tryptophan. While I3A was mechanistically linked to antitumor activity, intestinal homeostasis, and metabolic syndrome, capacity of gut microbes to produce other ArAs and their associations with host health remains relatively unexplored.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 4HBA, 4IA, and I3A, but not BA were reduced in feces from mice on and off a cocktail of poorly absorbed antibiotics that suppressed gut microbiota. Further, we identified multiple commensals with capacity to produce selected ArAs in culture and showed that individuals with irritable bowel disease (IBD) have lower levels of I3A, 4HBA, and 4IA, in their feces when compared to non-IBD controls, with all three being significantly lower in individuals with Chron's disease, but not in those with ulcerative colitis