The role of gut microbes in production of aromatic carboxaldehydes.

A stable isotope dilution mass spectrometry method based on derivatization with 3-methoxyphenylhydrazine was developed and validated for quantifying four aromatic carboxaldehydes (BA, 4HBA, 4IA, and I3A) derived from all four aromatic amino acids.

• The four aromatic carboxaldehydes measured were benzaldehyde (BA), 4-hydroxybenzaldehyde (4HBA), 4-imidazolecarboxaldehyde (4IA), and indole-3-carboxaldehyde (I3A).
• The method uses derivatization with 3-methoxyphenylhydrazine prior to mass spectrometry detection.
• The method was developed and validated for quantification from fecal samples.

Fecal levels of I3A and 4HBA were reduced in both human and mouse feces after treatment with a cocktail of nonabsorbable antibiotics that depleted the gut microbiota.

• The antibiotic treatment used was a cocktail of nonabsorbable antibiotics designed to deplete gut microbiota.
• Reductions in I3A and 4HBA were observed in both human and mouse fecal samples.
• BA was additionally reduced in humans following antibiotic treatment.
• 4IA was additionally reduced in mice following antibiotic treatment.

Multiple gut commensals were identified with the capacity to produce selected aromatic carboxaldehydes in culture.

• Commensal bacteria were tested for their ability to produce ArAs in culture conditions.
• Production capacity was identified for selected ArAs among multiple commensal species.
• This finding supports the gut microbial origin of fecal aromatic carboxaldehydes.

Individuals with Crohn's disease have lower fecal levels of I3A and 4HBA relative to non-inflammatory bowel disease controls, but this reduction was not observed in individuals with ulcerative colitis.

• The comparison was made between Crohn's disease patients, ulcerative colitis patients, and non-IBD controls.
• Both I3A and 4HBA were specifically reduced in Crohn's disease but not ulcerative colitis.
• This finding suggests disease-specific alterations in gut microbial aromatic carboxaldehyde production.
• I3A has been previously mechanistically linked to antitumor activity, intestinal homeostasis, and metabolic syndrome.

I3A is an aromatic carboxaldehyde synthesized by gut microbes from tryptophan and has been mechanistically linked to antitumor activity, intestinal homeostasis, and metabolic syndrome.

• I3A is derived from the aromatic amino acid tryptophan.
• Prior to this study, the capacity of gut microbes to produce other ArAs beyond I3A was largely unexplored.
• The lack of methods for detection and quantification of other ArAs had limited prior research in this area.