A recent study published in Nature on March 13 sheds light on the protective role of gut bacteria and a diet rich in the amino acid tryptophan against pathogenic E. coli infections. The research, led by Pamela Chang, associate professor of immunology in the College of Veterinary Medicine and of chemical biology in the College of Arts and Sciences, reveals how dietary tryptophan can be broken down by gut bacteria into metabolites that bind to receptors on gut epithelial cells, ultimately reducing the production of proteins that E. coli use to attach to the gut lining and cause infection.
Tryptophan, an amino acid primarily found in animal products, nuts, seeds, whole grains, and legumes, is metabolized by gut bacteria into small molecules that can inhibit the attachment of E. coli to the gut lining. The study identifies a previously unknown role for the dopamine receptor DRD2 in the gut, which acts as a sensor for microbial metabolites and helps protect against infection.
Samantha Scott, a postdoctoral researcher in Chang’s lab, served as the first author of the study, titled “Dopamine Receptor D2 Confers Colonization Resistance via Microbial Metabolites.” The findings suggest that DRD2 plays a dual role, acting as both a neurotransmitter receptor in the central and peripheral nervous systems and as a microbial metabolite sensor in the gut.
The research team used mice infected with Citrobacter rodentium, a bacterium similar to E. coli, to conduct experiments demonstrating the protective effects of tryptophan and gut bacteria against infection. By supplementing the mice’s diet with tryptophan and depleting gut microbes with antibiotics, they confirmed that protection from E. coli infection was dependent on both tryptophan and gut bacteria.
Using mass spectrometry, the researchers identified three tryptophan metabolites that were significantly increased in the gut when mice were fed a tryptophan-supplemented diet. These metabolites, when fed to mice alone, exhibited the same protective effect against infection as a full tryptophan diet.
Bioinformatics analysis led to the identification of the dopamine receptor DRD2 as the receptor responsible for mediating the protective effects of tryptophan metabolites in the gut. Further experiments with human intestinal cells revealed that activation of the DRD2 pathway compromised the host’s ability to produce an actin regulatory protein, which is essential for E. coli attachment to gut epithelial cells.
The study concludes that the activation of the DRD2 pathway prevents pathogenic bacteria from colonizing the gut by disrupting their ability to attach to gut epithelial cells. These findings provide insights into potential therapeutic targets for preventing E. coli infections and highlight the intricate relationship between diet, gut bacteria, and host immunity.