Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b

Abstract

The renewal and repair of intestinal epithelium depend on the self-renewal of intestinal stem cells (ISCs) under physiological and pathological conditions. Although previous work has established that exogenous nutrients regulate adult stem cell activity, little is known about the regulatory effect of L-arginine on ISCs. In this study we utilize mice and small intestinal (SI) organoid models to clarify the role of L-arginine on epithelial differentiation of ISCs. We show that L-arginine increases expansion of ISCs in mice. Furthermore, CD90+ intestinal stromal cells augment stem-cell function in response to L-arginine in co-culture experiments. Mechanistically, we find that L-arginine stimulates Wnt2b secretion by CD90+ stromal cells through the mammalian target of rapamycin complex 1 (mTORC1) and that blocking Wnt2b production prevents L-arginine-induced ISC expansion. Finally, we show that L-arginine treatment protects the gut in response to injury. Our findings highlight an important role for CD90+ stromal cells in L-arginine-stimulated ISC expansion.

Drosophila Undigested Metabolite Profiling reveals age related loss of intestinal amino acid transport regulates longevity

“…Interestingly, whether proliferation was impaired or stimulated depended on glutamate concentration 40 . L-arginine has also been shown to stimulate ISC expansion in mice 54 . Elevated activity of the amino acid sensing Target of Rapamycin (TOR) pathway, an established regulator of longevity, as a result of elevated amino acid levels may also have a role in intestinal decline.…”

“…In addition to impacts on the microbiota, some amino acids may have specific roles in intestinal health maintenance. For example, increased glutamate concentration has been shown to stimulate intestinal stem cell (ISC) proliferation in Drosophila 40 and in mice 59 and L-arginine has also shown to stimulate ISC expansion in mice 60 . Beyond the gut arginine has been shown to have a positive association with lifespan in a study of fibroblasts taken from a range of primate, avian and rodent species 61 and its supplementation increases the lifespan of C. elegans 62 .…”

Untargeted metabolomics analysis reveals spatial metabolic heterogeneity in different intestinal segments of type 1 diabetic mice

“…37 Arginine supplementation has been reported to alleviate intestinal damage and enhance intestinal immunity. [38][39][40] Histidine deficiency can result in intestinal epithelial cell apoptosis 41 and inflammatory response. 42 He et al found that dietary lysine enhanced villus height and crypt depth in the jejunum of weaned piglets.…”

Enhancing Growth and Gut Health in Squabs: The Impact of Fermented Mixed Feed

“…Arginine, which was enriched in the fermented-feed-treated squabs, has been reported to be an important amino acid for poultry, especially those under stress [41]. Arginine participates in the restoration of intestinal epithelial cells [42], and L-arginine can reduce intestinal mucosal injury induced by Clostridium perfringens colonization in broiler chickens [43]. Additionally, the contents of 1-arachidonoylglycerophosphoinositol, estradiol-17-phenylpropionate, aminotriazole, 3-benzoyloxy-6-oxo-12-ursen-28-oic acid, and PE (22:6/0:0) were decreased in the FMF group.…”