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 Mar 14. doi: 10.1021/acsinfecdis.3c00014.
Jing Liu  1 ,  Chengguo Zong  1 ,  Xin Yu  1 ,  Yan Ding  1 ,  Bing Chang  2 ,  Ruoyu Wang  3  4 ,  Lixuan Sang  5
Affiliations
  • 1. Clinical Laboratory, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Dalian 110006 Liaoning, China.
  • 2. Department of Gastroenterology, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning, China.
  • 3. Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Dalian 110006, Liaoning, China.
  • 4. The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian 116001, Liaoning, China.
  • 5. Department of Gastroenterology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang 110022, Liaoning, China.
PMID: 36917734 DOI: 10.1021/acsinfecdis.3c00014
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.
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