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

PLoS One. 2024 Jan 5;19(1):e0290493. doi: 10.1371/journal.pone.0290493. eCollection 2024.

Abstract

Currently, over 88 million people are estimated to have adopted 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. Sufficient uptake of cysteine is crucial, as it serves as substrate for protein synthesis and can be converted to taurine and glutathione. We found earlier that intermolecular cystine bridges are essential for the barrier function of the intestinal mucus layer. Therefore, we now investigate the effect of low dietary cystine on the intestine. Mice (8/group) received a high fat diet with a normal or low cystine concentration for 2 weeks. We observed no changes in plasma methionine, cysteine, taurine or glutathione levels or bile acid conjugation after 2 weeks of low cystine feeding. In the colon, dietary cystine restriction results in an increase in goblet cell numbers, and a borderline significant increase mucus layer thickness. Gut microbiome composition and expression of stem cell markers did not change on the low cystine diet. Remarkably, 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 increased epithelial proliferation. In conclusion, 2 weeks of cystine restriction did not result in apparent systemic effects, but the low cystine diet increased the proliferative capacity specifically of the small intestine and induced the number of goblet cells in the colon.

MeSH terms

  • Animals
  • Cysteine*
  • Cystine*
  • Glutathione
  • Humans
  • Intestine, Small
  • Mice
  • Taurine

Substances

  • Cystine
  • Cysteine
  • Glutathione
  • Taurine

Grants and funding

This work was financially supported by DSM Nutritional Products and the Dutch Technology Foundation STW (grant number 14940), which is the Applied Science Division of NWO (https://www.nwo.nl/), and Technology Programme of the Ministry of Economic Affairs. NI is further financially supported by the MLDS (https://www.mlds.nl/) Career Development Grant (CDG16-04) and by the Wilhelmina Children’s Hospital Research Fund (https://www.hetwkz.nl/nl/career-development). SvM is further financially supported by the Netherlands Organisation for Health Research and Development (ZonMW (https://www.zonmw.nl/nl); VICI grant, no: 09150181910029 and Aspasia grant, no: 015.015.013). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.