Generated by the breakdown of tryptophan, phenylalanine and tyrosine, indole and phenol metabolites play important roles in physiology, ranging from the maintenance of healthy body weight to immune regulation. They are also currently the focus of intense investigation for their roles in multiple diseases, including those of the liver and kidney, as well as their widely varying and even opposing influences on cancer pathogenesis and therapy. This species of metabolites is generally believed to be produced by gut bacteria, an assumption researchers led by Ludwig Princeton’s Jenna AbuSalim and Director Joshua Rabinowitz thought they’d put to the test. They reported in a June publication in Nature Metabolism that their isotope-tracing studies in mice, rats and human cells reveal that many indole and phenol metabolites—including such physiologically important ones as aryl-pyruvates, aryl-lactates, aryl-acetates, aryl-carboxylic acids and cinnamic acid—are, in fact, produced abundantly by mammalian metabolism. Circulating levels of the metabolites remained robust following treatment with antibiotics, which disrupt the microbiome. This finding was reflected in samples from patients on antibiotics, including cancer patients. Meanwhile, metabolites produced exclusively by microbes, such as indole-3-propionate and p-cresol sulfate, decreased following antibiotic treatment. Jenna, Josh and their colleagues also detailed the source of indole and phenol metabolites, information critical to understanding their physiological function and developing tools to manipulate their levels for therapy.
Host metabolism can produce many indoles and phenols independently of the microbiome
Nature Metabolism, 2026 June 23