MIT study finds cysteine boosts gut repair in mice

Researchers at MIT have discovered that the amino acid cysteine can enhance the small intestine's ability to heal itself. In experiments with mice, a cysteine-rich diet activated immune cells to promote tissue regeneration after damage from radiation or chemotherapy. The findings, published in Nature, suggest potential dietary strategies to mitigate treatment side effects.

A new study from the Massachusetts Institute of Technology reveals that cysteine, a common amino acid found in protein-rich foods, plays a key role in intestinal repair. Led by Omer Yilmaz, director of the MIT Stem Cell Initiative and associate professor of biology, the research focused on how individual nutrients affect stem cell regeneration in the gut.

The team fed mice diets high in one of 20 amino acids and found cysteine had the strongest effect, increasing both stem cells and progenitor cells in the small intestine. This process involves intestinal cells absorbing cysteine, converting it to CoA, which then activates CD8 T cells in the mucosal lining. These immune cells multiply and release IL-22, a signaling molecule that regulates stem cell regeneration and protects the intestinal lining from injury.

"What's really exciting here is that feeding mice a cysteine-rich diet leads to the expansion of an immune cell population that we typically don't associate with IL-22 production and the regulation of intestinal stemness," Yilmaz says. The activation was specific to the small intestine, where most dietary protein is absorbed.

In practical tests, mice on a cysteine-rich diet showed faster repair of radiation-induced damage to the gut lining. Unpublished work also indicated benefits after treatment with 5-fluorouracil, a chemotherapy drug used for colon and pancreatic cancers. "The study suggests that if we give these patients a cysteine-rich diet or cysteine supplementation, perhaps we can dampen some of the chemotherapy or radiation-induced injury," Yilmaz adds.

Cysteine is abundant in foods like meat, dairy, legumes, and nuts. While the body produces it from methionine in the liver, dietary sources deliver it directly to the gut. "With our high-cysteine diet, the gut is the first place that sees a high amount of cysteine," says lead author Fangtao Chi, a postdoctoral researcher at the Koch Institute.

The study, published in Nature in 2025, builds on prior work showing diets influence stem cell function but is the first to identify a single nutrient driving gut regeneration. Researchers plan to explore cysteine's effects on other tissues, such as hair follicles, and investigate additional amino acids for gut health.

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