There is a sizable literature of animal studies in which researchers increase or decrease intake of one specific dietary amino acid and observe the outcomes. Despite this, there are a lot of gaps and contradictory results in the understanding of the long term effects of increased intake of specific single amino acids, even for the smaller number of essential amino acids. Here, researchers find that increased cysteine intake can improve intestinal stem cell function in mice, and thus promote tissue health in the small intestine. While the context of the research is injury, such as the consequences of radiotherapy, this may be able to somewhat compensate for the loss of intestinal stem cell function that occurs with age.
A fundamental question in physiology is understanding how tissues adapt and alter their cellular composition in response to dietary cues. The mammalian small intestine is maintained by rapidly renewing LGR5+ intestinal stem cells (ISCs) that respond to macronutrient changes such as fasting regimens and obesogenic diets, yet how specific amino acids control ISC function during homeostasis and injury remains unclear.
Here we demonstrate that dietary cysteine, a semi-essential amino acid, enhances ISC-mediated intestinal regeneration following injury. Cysteine contributes to coenzyme A (CoA) biosynthesis in intestinal epithelial cells, which promotes expansion of intraepithelial CD8αβ+ T cells and their production of interleukin-22 (IL-22). This enhanced IL-22 signalling directly augments ISC reparative capacity after injury. The mechanistic involvement of the pathway in driving the effects of cysteine is demonstrated by several findings: CoA supplementation recapitulates cysteine effects, epithelial-specific loss of the cystine transporter SLC7A11 blocks the response, and mice with CD8αβ+ T cells lacking IL-22 or a depletion of CD8αβ+ T cells fail to show enhanced regeneration despite cysteine treatment.
These findings highlight how coupled cysteine metabolism between ISCs and CD8+ T cells augments intestinal stemness, providing a dietary approach that exploits ISC and immune cell crosstalk for ameliorating intestinal damage.
