Dietary cystine restriction increases the proliferative capacity of the small intestine of mice
Cysteine is a semi-essential amino acid, because although cells can produce cysteine from methionine, its availability is largely dependent on dietary intake of cysteine, cystine and methionine present in meat, eggs and whole grains. The majority of dietary cystine is absorbed in the small intestine and used for protein synthesis or conversion to taurine and glutathione. Since there is a trend towards adopting a vegetarian/vegan diet, which is inherently low in cysteine, we investigate the effect of dietary cystine restriction on intestinal epithelial layer function. Mice (8/group) received a high fat diet or this diet low in cystine for 2 weeks. We observed no changes in plasma methionine, cysteine, taurine or glutathione levels after 2 weeks. Stem cell markers as well as the proliferation marker Ki67 were or tended to be significantly increased upon cystine restriction in the small intestine. Gene set enrichment analysis reveals enrichment of Wnt signaling in the small intestine of mice on the low cystine diet. These proliferative effects were not observed in the colon. In the colon, dietary cystine restriction results in an increased number of goblet cells, but no significant changes in the thickness of the mucus barrier or in its protective capacity. There was no difference in the microbiome between the normal and low cystine diet. Overall, we cannot conclude if dietary cystine restriction is beneficial, since increased proliferation and goblet cells may be an indication of damage repair or absorptive surface enlargement for more efficient cysteine uptake.