Alanyl-Glutamine (Ala-Gln) Ameliorates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by Regulating the Gut Microbiota, PI3K-Akt/NF-κB/STAT3 Signaling, and Associated Pulmonary Injury

ACS Infect Dis. 2023 Apr 14;9(4):979-992. doi: 10.1021/acsinfecdis.3c00014. Epub 2023 Mar 14.

Abstract

The aim of this study was to investigate the protective effect of alanyl-glutamine (Ala-Gln) on acute colitis complicated by pulmonary injury induced by dextran sulfate sodium (DSS) in C57BL/6 mice. The results showed that Ala-Gln intervention alleviated weight loss, the disease activity index (DAI), colon shortening, and pathological injury and regulated the absolute number of CD4+T-cell subsets in mesenteric lymph nodes (MLNs). In addition, Ala-Gln intervention significantly ameliorated the composition of the gut microbiota in mice with DSS- induced acute colitis, significantly decreasing the relative abundance of Desulfovibrionaceae and increasing the abundances of Gastranaerophilales, Clostridia-vadinBB60, and Alistipes. Moreover, Ala-Gln treatment significantly inhibited the activation of the PI3K-Akt/NF-κB/STAT3 inflammatory signaling pathways in the colon of mice with DSS-induced acute colitis. Notably, Ala-Gln intervention also alleviated the pulmonary injury as well as the imbalance in levels of CD4+T-cell subsets in pulmonary tissue in mice with DSS-induced acute colitis. In conclusion, Ala-Gln alleviates DSS-induced acute colitis by regulating the gut microflora and PI3K-Akt/NF-κB/STAT3 signaling pathways, as well as by alleviating accompanying pulmonary injury.

Keywords: alanyl-glutamine (Ala-Gln); colitis; gut microbiota; pulmonary injury; signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Colitis* / metabolism
  • Cytokines / metabolism
  • Dextran Sulfate / toxicity
  • Gastrointestinal Microbiome*
  • Lung Injury*
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • NF-kappa B / pharmacology
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt

Substances

  • alanylglutamine
  • Cytokines
  • Dextran Sulfate
  • NF-kappa B
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Stat3 protein, mouse