Dietary tryptophan may offer protection against E. coli infection: Study

Dietary tryptophan – an amino acid found mostly in animal products, nuts, seeds, whole grains, and legumes – can be broken down by gut bacteria into small molecules called metabolites which can bind to a receptor on gut epithelial (surface) cells, triggering a pathway that ultimately reduces the production of proteins that E. coli uses to attach to the gut lining where they cause infection. When E. coli fail to attach and colonize the gut, the pathogen benignly moves through and passes out of the body.

Dopamine Receptor D2, or DRD2, present in peripheral tissues such as the gastrointestinal tract, plays a crucial role in gut function and helps regulate various gastrointestinal processes, including motility, secretion, and sensation.

“It’s actually two completely different areas that this receptor could play a role in, which was not appreciated prior to our findings,” said Pamela Chang, associate professor of immunology in the College of Veterinary Medicine and of chemical biology in the College of Arts and Sciences. “We essentially think that DRD2 is moonlighting in the gut as a microbial metabolite sensor, and then its downstream effect is to help protect against infection.”

In the study, researchers used mice infected with C. rodentium, similar to E. coli, to study the protective effects of tryptophan in the gut. They found that a tryptophan-supplemented diet reduced pathogen levels and inflammation in the mice. Depleting gut bacteria with antibiotics removed this protective effect, confirming the role of gut microbes. Mass spectrometry identified three tryptophan metabolites boosted by the diet, each replicating the protective effect. Activation of DRD2 in human gut cells disrupted actin production, preventing pathogens like C. rodentium and E. coli from causing infection.

The findings revealed a new role of dopamine receptor DRD2 in the gut that controls actin proteins and affects a previously unknown pathway for preventing a pathogenic bacteria’s ability to colonize the gut.

Reference: Samantha A. Scott, Jingjing Fu & Pamela V. Chang; Journal: Nature; DOI: 10.1038/s41586-024-07179-5