Credit: iScience (2026). DOI: 10.1016/j.isci.2026.114680

Many biological processes exhibit daytime differences governed by rhythmic exposure to sunlight, termed circadian rhythms. Researchers at Penn State recently found, in mice, that a protein critical to intestinal barrier function—helping the gut absorb nutrients while blocking harmful pathogens—is rhythmically controlled by nighttime liver metabolism of the molecule tryptophan.

In this study, published in the journal iScience, researchers found that when tryptophan—an amino acid needed to synthesize vital proteins—is ingested, it travels to the liver. There, tryptophan produces metabolites—molecular byproducts of metabolism—that activate a protein called the aryl hydrocarbon receptor (Ah receptor), which then works to improve barrier function in the gut.

Gary Perdew, the H. Thomas and Dorothy Willits Hallowell Chair in Agricultural Sciences and lead author on the paper, said that the findings provide clues as to how diet can be used to improve intestinal barrier function.

"Ingesting tryptophan, which is plentiful in protein-rich foods, kickstarts this process that results in better barrier function in the gut, suggesting that protein is a really important part of your diet," he said, explaining that, even though this work was conducted in mice, the Ah receptor is abundant in humans. "We also observed that this process increases during waking hours, indicating it might be even more important to have protein at breakfast."

The Ah receptor is found in many types of tissues in the human body, the researchers said, but it is more plentiful in the lungs, liver, skin and intestinal tract.

Previous research from the team found that when Ah receptor is blocked in the intestinal tract, negative effects followed, including altered transit time of food in the small intestine and decreased amounts of protective mucus.

While their previous study found that cruciferous vegetables like broccoli had a positive effect on this process and resulted in better gut health, the researchers said they suspected that there were other ways the body activates Ah receptor to help maintain overall health.

"It’s clear that this receptor is very important for maintaining barrier homeostasis in our intestinal tract," Perdew said. "And we hypothesized that if this receptor is important for barrier function, especially in your intestinal tract, there’s probably a process within the body that isn’t completely dependent on the right diet."

For this study, the researchers fed the mice on a schedule meant to mimic how humans usually eat. They restricted food from the mice during the hours of the day, when they’re typically sleeping, and reintroduced food during the evening, when mice are more active. This approach mirrors how humans fast overnight and then eat breakfast in the morning.

The researchers analyzed mouse liver and serum every four hours, which allowed them to observe the effect of tryptophan ingestion in mice. They discovered that the period of an animals’ circadian rhythm during which active eating occurs leads to an increase in tryptophan metabolites produced in the liver and are present in serum.

"This, in turn, leads to an increase in Ah receptor activity," Perdew said. "And based on our previous findings of the role of the Ah receptor, this would likely lead to enhanced barrier tissue function."

Publication details

Ethan W. Morgan et al, Circadian tryptophan metabolism contributes to systemic aryl hydrocarbon receptor activity, iScience (2026). DOI: 10.1016/j.isci.2026.114680

Journal information: iScience

Citation: Liver metabolism of an essential amino acid may play a key role in gut health (2026, February 2) retrieved 2 February 2026 from https://medicalxpress.com/news/2026-02-liver-metabolism-essential-amino-acid.html

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