MIT researchers have discovered that a naturally occurring amino acid found in many protein-rich foods may help the intestine repair itself after damage. In a new study, scientists found that cysteine can activate an immune response that boosts intestinal stem cells and helps regenerate tissue in the small intestine.
The findings, which were observed in mice, could eventually lead to new ways to reduce intestinal damage caused by radiation therapy and chemotherapy. Researchers say cysteine-rich diets or supplements might one day help cancer patients recover more quickly from treatment-related injuries.
"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," says Omer Yilmaz, director of the MIT Stem Cell Initiative, an associate professor of biology at MIT, and a member of MIT's Koch Institute for Integrative Cancer Research. "The beauty here is we're not using a synthetic molecule; we're exploiting a natural dietary compound."
The study, published in Nature, is the first to identify a single nutrient capable of directly enhancing intestinal stem cell regeneration. Previous research had shown that broader dietary patterns, such as fasting or calorie restriction, can influence stem cell activity, but scientists had not pinpointed one specific nutrient responsible for this type of repair response.
Yilmaz and his team wanted to better understand how individual nutrients affect stem cells and tissue health. To investigate, the researchers fed mice diets enriched with one of 20 different amino acids, which are the building blocks of proteins. They then measured how each amino acid influenced regeneration in intestinal stem cells.
Among all the amino acids tested, cysteine produced the strongest regenerative effect on both stem cells and progenitor cells, which eventually mature into adult intestinal cells.
The researchers later uncovered the biological chain reaction behind the effect. When intestinal cells absorb cysteine from food, they convert it into a molecule called CoA. That molecule is then released into the intestinal lining, where it is absorbed by immune cells known as CD8 T cells.
Once activated, these T cells begin multiplying and producing IL-22, a signaling protein called a cytokine that plays a major role in intestinal repair and stem cell regeneration.
Until now, scientists did not know that CD8 T cells could produce IL-22 in a way that supports intestinal stem cells.
"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. "What happens in a cysteine-rich diet is that the pool of cells that make IL-22 increases, particularly the CD8 T-cell fraction."
The researchers found that these activated T cells gather in the lining of the small intestine, placing them in an ideal position to respond quickly when damage occurs. The effect was largely limited to the small intestine because that is where most dietary protein is absorbed.
In the study, mice fed a cysteine-rich diet showed improved recovery from radiation-related intestinal damage. The team also reports that unpublished experiments found similar regenerative benefits after treatment with the chemotherapy drug 5-fluorouracil, which is commonly used against colon and pancreatic cancers but can also injure the intestinal lining.
Cysteine occurs naturally in many high-protein foods, including meat, dairy products, legumes, and nuts. The human body can also produce cysteine on its own by converting another amino acid called methionine in the liver.
However, researchers say dietary cysteine appears to have a stronger effect on the intestine because it reaches the gut directly before being distributed throughout the body.
"With our high-cysteine diet, the gut is the first place that sees a high amount of cysteine," Chi says.
Cysteine has long been known for its antioxidant properties, but this is the first study showing that it can directly stimulate intestinal stem cell regeneration.
The MIT team is now exploring whether cysteine may also support regeneration in other tissues. One ongoing project is examining whether the amino acid can stimulate hair follicle repair and regrowth.
Researchers are also continuing to investigate the effects of other amino acids that showed signs of influencing stem cell behavior.
"I think we're going to uncover multiple new mechanisms for how these amino acids regulate cell fate decisions and gut health in the small intestine and colon," Yilmaz says.
The research was supported in part by the National Institutes of Health, the V Foundation, the Kathy and Curt Marble Cancer Research Award, the Koch Institute-Dana-Farber/Harvard Cancer Center Bridge Project, the American Federation for Aging Research, the MIT Stem Cell Initiative, and the Koch Institute Support (core) Grant from the National Cancer Institute.
