Abstract
Inflammatory bowel disease (IBD) is a chronic intestinal disorder threatening human health. Di-peptide alanyl-glutamine (Ala-Gln) has various beneficial effects on gut health. However, its role and functional mechanism in treating IBD are still not clear. Therefore, the protective effects of Ala-Gln and glutamine (Gln) on dextran sulfate sodium- (DSS-) induced colitic mice were investigated in this study. The results showed that oral supplementation of Ala-Gln or Gln significantly attenuated the colitis symptoms in mice, including body weight loss, colon length, disease activity index, histological scores, and tissue apoptosis. The concentrations of interleukin- (IL-) 1β, IL-6, tumor necrosis factor-α, and myeloperoxidase were significantly decreased, while the concentrations of immunoglobulins (IgA, IgG, and IgM) and superoxide dismutase were significantly increased by Ala-Gln or Gln supplementation. The expression of occludin and peptide transporter 1 (PepT1) was significantly increased by Ala-Gln or Gln. Interestingly, Ala-Gln had better beneficial effects than Gln in alleviating colitis. In addition, 16S rDNA sequencing showed that the DSS-induced shifts of the microbiome (community diversity, evenness, richness, and composition) in the mouse colon were restored by Gln and Ala-Gln, including Lactobacillus, Bacteroides_acidifaciens, Bacteroidales, Firmicutes, Clostridia, Helicobacter, and Bacteroides. Correspondingly, the functions of the microflora metabolism pathways were also rescued by Ala-Gln, including fatty acid metabolism, membrane transporters, infectious diseases, and immune system. In conclusion, the results revealed that Ala-Gln can prevent colitis through PepT1, enhancing the intestinal barrier and modulating gut microbiota and microflora metabolites.
Highlights
Inflammatory bowel disease (IBD, including ulcerative colitis) is a chronic gastrointestinal disorder caused by inflammation or oxidative stress in the colon, which has threatened the human health and has various colitis symptoms, such as gut bleeding, bloody diarrhea, body weight (BW) loss, epithelial cell loss, neutrophil infiltration, and the release of proinflammatory mediators (e.g., interleukin(IL-) 1β, IL-4, IL-5, IL-6, IL-8, and tumor necrosis factor(TNF-) α) [1]
The treatment of Gln did not significantly alleviate dextran sulfate sodium- (DSS-)induced mouse colitis. These results suggested that the DSS-induced colitis symptom was dramatically alleviated by Ala-Gln
This study reveals that the oral administration of Gln and Ala-Gln can protect against DSS-induced colitis through alleviating mucosa damage and inflammatory responses, upregulating the expression of tight junction (TJ) and peptide transporter 1 (PepT1) proteins and modulating gut microbiota in mice
Summary
Inflammatory bowel disease (IBD, including ulcerative colitis) is a chronic gastrointestinal disorder caused by inflammation or oxidative stress in the colon, which has threatened the human health and has various colitis symptoms, such as gut bleeding, bloody diarrhea, body weight (BW) loss, epithelial cell loss, neutrophil infiltration, and the release of proinflammatory mediators (e.g., interleukin(IL-) 1β, IL-4, IL-5, IL-6, IL-8, and tumor necrosis factor(TNF-) α) [1]. The application of bioactive peptides with the potential to manage chronic intestinal inflammation comes into people’s view [1]. Glutamine (Gln) is a well-studied amino acid with immune-modulating effects [2, 3], and it can alleviate intestinal inflammation [4]. Gln used in human and animal studies is often in the form of alanylglutamine (Ala-Gln) [3]. The difference of the effects between Ala-Gln and Gln is still not clear. Ala-Gln has a superior preventive effect on intestinal damage with more mucosal weight, protein content, and Oxidative Medicine and Cellular Longevity villus height than those in mice with alanine plus Gln mixture [7]. AlaGln may serve as a bioactive peptide and has better effects than Gln or alanine alone
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