The Effects of Dietary Glycine on the Acetic Acid-Induced Mouse Model of Colitis

Abstract

Inflammatory bowel disease, a gut disease that is prevalent worldwide, is characterized by chronic intestinal inflammation, such as colitis, and disorder of the gut microbiome. Glycine (Gly) is the simplest amino acid and functions as an anti-inflammatory immune-nutrient and intestinal microbiota regulator. This study aimed at investigating the effect of Gly on colitis induced in mice by intrarectal administration of 5% acetic acid (AA). Bodyweight and survival rates were monitored, and colonic length and weight, serum amino acid concentrations, intestinal inflammation-related gene expression, and colonic microbiota abundances were analyzed. The results showed that Gly dietary supplementation had no effect on the survival rate or the ratio of colonic length to weight. However, Gly supplementation reversed the AA-induced increase in serum concentrations of amino acids such as glutamate, leucine, isoleucine, and valine. Furthermore, Gly inhibited colonic gene expression of interleukin- (IL-) 1β and promoted IL-10 expression in colitis mice. Gly supplementation also reversed the AA-induced reduction in the abundance of bacteria such as Clostridia, Ruminococcaceae, and Clostridiales. This change in the intestinal microbiota was possibly attributable to the changes in colonic IL-10 expression and serum concentrations of valine and leucine. In sum, Gly supplementation regulated the serum concentrations of amino acids, the levels of colonic immune-associated gene expression, and the intestinal microbiota in a mouse model of colitis. These findings enhance our understanding of the role of Gly in regulating metabolism, intestinal immunity, and the gut microbiota in animals afflicted with colitis.

Glycine Attenuates Citrobacter rodentium‐Induced Colitis by Regulating ATF6‐Mediated Endoplasmic Reticulum Stress in Mice

“…Consistent with previous studies, [ 30,32 ] we found that Gly administration alleviated C. rodentium ‐induced colitis. Mechanistically, this beneficial effect may be associated with the inhibition of epithelial cell apoptosis mediated by the ATF6α/CHOP signaling, inactivation of colonic inflammatory responses, and increased Lactobacillus in the colon.…”

“…The protective effects of Gly against experimental colitis may be associated with suppressing the secretion of pro‐inflammatory cytokines. [ 30,32 ] In agreement with previous findings, the increase in pro‐inflammatory cytokines in serum was abolished by Gly. As pro‐inflammatory cytokines could facilitate inflammatory responses through the recruitment of inflammatory cells and contribute to tissue damage, the reduced infiltration of inflammatory cells was also observed in the colon tissues of mice supplemented with Gly.…”

“…Consistently, Gly has been reported to regulate the intestinal microbiota in chemical reagent‐induced colitis and an animal model of nonalcoholic fatty liver disease. [ 30,31 ] Gly has also been reported to alleviated TNBS‐induced and DSS‐induced colitis in rats, as well as acetic acid‐induced colitis in mice. [ 30,32 ] However, the protective effects of Gly against C. rodentium ‐induced colitis in mice and the underlying mechanisms remain elusive.…”

“…[ 30,31 ] Gly has also been reported to alleviated TNBS‐induced and DSS‐induced colitis in rats, as well as acetic acid‐induced colitis in mice. [ 30,32 ] However, the protective effects of Gly against C. rodentium ‐induced colitis in mice and the underlying mechanisms remain elusive. In the present study, we hypothesized that Gly may alleviate C. rodentium ‐induced colitis by suppressing ER stress and inflammatory responses, and restoring the intestinal microbial community.…”

Responses of Intestinal Microbiota and Immunity to Increasing Dietary Levels of Iron Using a Piglet Model

“…16S rDNA sequencing of cecal and colonic microbiota was used for intestinal microbiota analysis according to our previous study (Wu et al, 2020). Briefly, the DNA was extracted from cecal and colonic digesta by Qiagen QIAamp DNA Stool Mini kit (Qiagen, Hilden, Germany) according to the manufacturer's recommendation.…”