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A regimen abundant in the amino acid cysteine might possess revitalizing effects in the small intestine, as indicated by a recent investigation from MIT. The researchers uncovered that this amino acid can activate an immune signaling pathway that assists stem cells in regenerating new intestinal tissue.
This improved regeneration may facilitate the healing of injuries caused by radiation, which frequently occur in individuals undergoing radiation therapy for cancer. The study was performed on mice, but if forthcoming research reveals corresponding outcomes in humans, then administering heightened amounts of cysteine, through nutrition or supplements, could provide a novel approach to accelerate tissue recovery, the researchers assert.
“The study implies that if we provide these patients with a cysteine-rich nourishment or cysteine supplementation, perhaps we can mitigate some of the chemotherapy or radiation-induced damage,” remarks Omer Yilmaz, head 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 advantage here is that we’re not utilizing a synthetic compound; we’re leveraging a natural dietary substance.”
While earlier investigations have demonstrated that specific varieties of diets, like low-calorie regimens, can boost intestinal stem cell activity, this fresh study is the first to pinpoint a single nutrient that aids intestinal cells in rejuvenation.
Yilmaz is the senior author of the study, which was published today in Nature. Koch Institute postdoctoral researcher Fangtao Chi serves as the lead author of the paper.
Enhancing regeneration
It is widely acknowledged that diet can influence overall wellness: High-fat nutrition can result in obesity, diabetes, and other health concerns, while low-calorie diets have been shown to prolong lifespans in numerous species. Recently, Yilmaz’s laboratory has explored how various diets affect stem cell regeneration and discovered that high-fat regimens, along with brief intervals of fasting, can elevate stem cell activity in diverse manners.
“We understand that dietary patterns, such as those high in sugar, high in fat, and low in calories, have a notable effect on health. However, on a deeper level, we know considerably less regarding how individual nutrients influence stem cell fate choices, as well as tissue function and overall tissue health,” states Yilmaz.
In their updated examination, the researchers initiated by providing mice a diet rich in one of 20 distinct amino acids, the building blocks of proteins. For each cohort, they evaluated how the diet impacted intestinal stem cell regeneration. Among these amino acids, cysteine exhibited the most significant influence on stem cells and progenitor cells (immature cells that develop into adult intestinal cells).
Subsequent investigations indicated that cysteine starts a cascade of events leading to the activation of a group of immune cells known as CD8 T cells. When cells in the intestinal lining absorb cysteine from digested food, they convert it into CoA, a cofactor released into the mucosal lining of the intestine. There, CD8 T cells take in CoA, prompting them to initiate proliferation and produce a cytokine labeled IL-22.
IL-22 is a crucial element in regulating intestinal stem cell regeneration; however, it was previously unknown that CD8 T cells could produce it to enhance intestinal stem cells. Once stimulated, those IL-22-secreting T cells are prepared to assist in addressing any injury that might occur within the intestinal lining.
These T cells are inclined to gather within the intestinal lining, thus they are ideally positioned when needed. The researchers discovered that CD8 T cell stimulation primarily occurred in the small intestine, rather than any other section of the digestive system, which they attribute to the fact that the majority of the protein consumed is absorbed by the small intestine.
Restoring the intestine
In this research, the investigators demonstrated that regeneration induced by a cysteine-rich diet could assist in repairing radiation damage to the intestinal lining. Additionally, in research that has yet to be published, they found that a high-cysteine diet had a restorative effect following treatment with a chemotherapy agent known as 5-fluorouracil. This medication, used for colon and pancreatic cancers, can also harm the intestinal lining.
Cysteine is present in various high-protein foods, such as meat, dairy products, legumes, and nuts. The body can also generate its own cysteine by converting the amino acid methionine to cysteine — a process occurring in the liver. However, cysteine produced in the liver is circulated throughout the body and does not accumulate in the small intestine the same way that dietary cysteine consumption does.
“With our high-cysteine nourishment, the gut is the initial location that encounters a heightened amount of cysteine,” Chi notes.
Cysteine has previously been recognized for its antioxidant properties, which are also advantageous; yet this research is the first to reveal its impact on intestinal stem cell regeneration. The researchers now aim to explore whether it may also encourage other varieties of stem cells to regenerate new tissues. In an ongoing study, they are examining whether cysteine could stimulate hair follicle regeneration.
They also intend to further investigate some of the other amino acids that appear to affect stem cell rejuvenation.
“I believe we are going to unveil multiple new mechanisms by which these amino acids govern cell fate choices and gut health in the small intestine and colon,” concludes Yilmaz.
The study was partially supported 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.
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