ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1437662
Deglycosylated azithromycin Alleviates cisplatin-evoked Constipation in Mice by Altering Host Metabolome and Gut Microbiota Composition
Provisionally accepted
Xiaoyu Ai*
Xiaoting Gu
Shuwen Zhu
Weixue Tian
Xiaohe LiYutian CaiChaoyue ZhengXiang XuConglu ZhaoHongting LiuYao SunZhilin Luo
Honggang ZhouCheng Yang- College of Pharmacy, Nankai University, Tianjin, China
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Chemotherapy induced constipation (CIC) is a gastrointestinal side effect that occurs in patients receiving chemotherapy, which can further deteriorate the living quality of cancer patients. Deglycosylated azithromycin (Deg-AZM), a newly developed Class I drug with good therapeutic effects on chronic constipation, has been approved for clinical trials in 2024.However, it is unclear whether Deg-AZM has any impact on gut microbiota of CIC mice. The purpose of this study was to explore the role of Deg-AZM in treating CIC by modulating the gut microbiota. The results showed that Deg-AZM significantly enhanced intestinal motility in the mice with cisplatin-evoked constipation. Additionally, the regulation of intestinal microbiota by Deg-AZM was analyzed through 16S rRNA sequencing, and changes in metabolites were examined using untargeted metabolomics. The results of gut microbiota showed that Deg-AZM altered the community composition by decreasing Deferribacterota and Pseudomonadota and increasing Bacteroidota, Lactobacillus and Muribaculaceae. The feces metabolomics revealed that alanine, aspartate and glutamate metabolism, citrate cycle (TCA cycle), purine metabolism, primary bile acid biosynthesis and taurine and hypotaurine metabolism in CIC model were modulated by Deg-AZM. In conclusion, Deg-AZM could alleviate cisplatin-evoked constipation in mice by reshaping the structure of gut microbial community, which may provide a potential basis for the use and clinical development of Deg-AZM for CIC treatment.
Keywords: 38 Tongyan Road, Jinnan District, Tianjin, P.R.China 300350 Deg-AZM, Pharmacodynamic, 16S rRNA, Untargeted metabolomics chemotherapy induced constipation, CIC, deglycosylated Azithromycin, Deg-AZM, human metabolome database, HMDB, Kyoto Encyclopedia of Genes and Genomes database, KEGG, Lipid metabolites and pathways strategy database, LIPID MAPS, fold change, FC, variable importance in the projection, VIP, operational taxonomic units, OTUs
Received: 24 May 2024; Accepted: 15 Apr 2025.
Copyright: © 2025 Ai, Gu, Zhu, Tian, Li, Cai, Zheng, Xu, Zhao, Liu, Sun, Luo, Zhou and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoyu Ai, College of Pharmacy, Nankai University, Tianjin, China
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