Dietary cystine restriction increases the proliferative capacity of the small intestine of mice

Abstract

Over 88 million people are currently estimated to have adopted towards a vegan or vegetarian diet. Cysteine is a semi-essential amino acid, which availability is largely dependent on dietary intake of meat, eggs and whole grains. Vegan/vegetarian diets are therefore inherently low in cysteine concentrations. Sufficient uptake of cysteine is crucial, as it serves as substrate for protein synthesis and conversion to taurine and glutathione. In this study, we therefore investigate the effect of low dietary cystine, the oxidized derivative of cysteine, on intestinal epithelial layer function. Mice (8/group) received a high fat diet with normal or low cystine concentration 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 increased upon cystine restriction in the small intestine. In line with this, gene set enrichment analysis indicated enrichment of Wnt signaling in the small intestine of mice on the low cystine diet, indicative of proliferative cells. Increased proliferation was absent in the colon. In the colon, dietary cystine restriction results in an increase in goblet cells, but no significant changes in the thickness of the mucus barrier or in its protective capacity. Also the microbiome was not changed upon dietary restriction. In conclusion, we show that cystine restriction for two weeks does not seem to induce any systemic effects. The increased proliferative capacity and number of goblet cells observed in the intestine may be the effect of starting epithelial damage or a reaction of the epithelium to start enlarging the absorptive capacity.