A new study from MIT suggests that eating foods rich in the amino acid cysteine could help renew and repair the small intestine. Researchers found that cysteine can activate an immune signaling process that stimulates stem cells to form new intestinal tissue. This enhanced regenerative ability could help the body heal damage from radiation, which is a common side effect of cancer treatments. Although the study was conducted on mice, scientists say that if similar results are observed in humans, cysteine from food or supplements could provide a new way to regenerate the gut more quickly after injury.
Nutrition and Regeneration
“The study suggests that by providing a cysteine-rich diet or cysteine supplementation to these patients, we may be able to mitigate some of the damage caused by chemotherapy or radiation,” says Omer Yilmaz, director of the MIT Stem Cell Initiative, associate professor of biology at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research. “The beauty of this is that we’re not using a synthetic molecule, we’re using a natural food composition.” Previous studies have shown that certain types of diet, including calorie restriction, can improve intestinal stem cell function. However, this research is the first to identify a single nutrient that directly promotes the gut’s regenerative capacity. Yilmaz is the lead author of the study, which was recently published in Nature. The lead author of the paper is Fangtao Chi, a postdoctoral fellow at the Koch Institute.
It is well known that diet plays an important role in health. A high-fat diet can contribute to obesity, diabetes and other chronic diseases, while a low-calorie diet is associated with a longer lifespan in many species. Yilmaz’s lab has long studied how different diets affect stem cell regeneration and has already shown that both a high-fat diet and short-term fasting can increase stem cell activity in different ways. “We know that macro diets such as high-sugar, high-fat and low-calorie diets have a clear impact on health. However, at a granular level, we know much less about how individual nutrients influence stem cell fate decisions as well as tissue function and overall tissue health,” says Yilmaz.
The Role of Cysteine
In their latest work, the MIT team fed mice a diet rich in one of 20 amino acids, the building blocks of proteins. They then analyzed how each amino acid affected the growth of stem cells in the intestine. Cysteine had the strongest effect, significantly increasing the number of both stem cells and progenitor cells (immature cells that develop into adult intestinal cells). Further experiments showed that cysteine triggers a chain reaction that activates immune cells known as CD8 T cells. When intestinal cells absorb cysteine from food, they convert it into CoA, a cofactor that enters the intestinal mucosa. There, CD8 T cells take up CoA, which triggers them to proliferate and release a signaling molecule called IL-22. IL-22 plays an important role in regulating the regeneration of intestinal stem cells, but until now scientists did not know that CD8 T cells could produce it. Once activated, these IL-22-releasing T cells help to protect and repair the intestinal mucosa when it is injured.
“What’s really exciting is that a cysteine-containing diet in mice leads to an increase in an immune cell population that we don’t normally associate with IL-22 production and regulation of intestinal stem cells,” says Yilmaz. “A cysteine-rich diet increases the pool of cells that produce IL-22, especially the proportion of CD8 T cells.” These T cells tend to accumulate in the intestinal mucosa, which puts them in the right place to respond quickly to damage. The researchers observed that the activation of CD8 T cells occurred mainly in the small intestine and not elsewhere in the digestive tract, probably because this is where most of the dietary proteins are absorbed.
Repairing Damage Caused by Radiotherapy and Chemotherapy
In the study, mice fed a cysteine-rich diet showed improved repair of radiation damage to the intestinal mucosa. In additional unpublished work, the team found that the same diet supported regeneration after treatment with 5-fluorouracil, a chemotherapeutic agent commonly used for colon and pancreatic cancer that can also damage intestinal tissue. Cysteine occurs naturally in many protein-rich foods, including meat, dairy products, legumes and nuts. The body can also produce cysteine itself by converting another amino acid, methionine, in the liver. However, the cysteine produced internally circulates throughout the body and does not concentrate in the intestines like the cysteine ingested through food.
“In our cysteine-rich diet, the gut is the first place where a high amount of cysteine arrives,” says Chi. Cysteine has long been known for its antioxidant properties, but this study is the first to show that it also supports the regeneration of intestinal stem cells. The researchers are now investigating whether cysteine can also stimulate the regeneration of other tissues. An ongoing project is testing whether cysteine can promote the regrowth of hair follicles. They also plan to investigate other amino acids that may influence stem cell regeneration and intestinal health.