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甘草泻心汤通过调节肠道菌群和代谢物改善小鼠溃疡性结肠炎
Authors Luo YT, Wu J, Zhu FY, Wu JQ, Wu P, Liu YC
Received 11 December 2021
Accepted for publication 25 April 2022
Published 9 May 2022 Volume 2022:16 Pages 1383—1405
DOI https://doi.org/10.2147/DDDT.S352467
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Georgios D. Panos
Purpose: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that starts with mucosal inflammation of the rectum and extends proximally in the colon in a continuous manner over a variable distance. Although it is more common in North America and Western Europe, its incidence is also increasing in Asia. Despite the introduction of several different classes of medications, the treatment options for UC may be insufficiently effective and burdened with significant side effects. In the present study, the therapeutic effects of Gancao Xiexin decoction (GCXX) were investigated on mice with dextran sulfate sodium (DSS)-induced colitis with exploration of the underlying mechanisms.
Methods: Colitis was induced in C57BL/6 mice by administering 3% DSS in drinking water for 7 days. GCXX and (or) the standard of care anti-inflammatory drug, mesalazine (5-aminosalicylic acid) were then administered for 7 days. The gut microbiota was characterized by 16S rDNA high-throughput gene sequencing and gut metabolites were detected by untargeted metabolomics. Germ-free mice were subsequently used to determine whether GCXX ameliorated UC principally through modulation of the gut microbiota.
Results: GCXX treatment was demonstrated to significantly reduce disease activity index (DAI) scores, prevent colonic shortening, ameliorate colonic tissue damage and reduce the levels of pro-inflammatory cytokines. Furthermore, analysis of the gut microbiota showed that GCXX-treated mice had higher relative quantity of Dubosiella (P< 0.05) and lower relative quantity of Escherichia-Shigella (P< 0.05). Metabolomics analysis indicated that GCXX could reduce the level of linoleic acid (P< 0.05) and regulate its metabolism pathway. Moreover, in germ-free mice, GCXX failed to increase body weight, reduce DAI scores, or alleviate either colonic shortening or colonic damage.
Conclusion: The present study demonstrated that GCXX ameliorated DSS-induced colitis principally through modulating the gut microbiota and metabolites. This information should be integrated into the overall mechanisms of GCXX treatment of UC.
Keywords: gancao xiexin decoction, ulcerative colitis, gut microbiota, metabolomics, germ-free mice, dubosiella , Escherichia-Shigella , linoleic acid