{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:35:55Z","timestamp":1792089355572,"version":"4.4.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The therapeutic effects of Deg-AZM on intestinal motility were assessed in a cisplatin-induced CIC mouse model. The gut microbiota composition was analyzed using 16S rRNA sequencing, and metabolic changes were evaluated through untargeted metabolomics of fecal samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Deg-AZM significantly enhanced intestinal motility in the mice with cisplatin-evoked constipation. Gut microbiota analysis revealed that Deg-AZM altered the community composition by decreasing <jats:italic>Deferribacterota<\/jats:italic> and <jats:italic>Pseudomonadota<\/jats:italic> and increasing <jats:italic>Bacteroidota<\/jats:italic>, <jats:italic>Lactobacillus<\/jats:italic> and <jats:italic>Muribaculaceae<\/jats:italic>. 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1437662","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T21:30:51Z","timestamp":1747863051000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Deglycosylated azithromycin alleviates cisplatin-evoked constipation in mice by altering host metabolome and gut microbiota composition"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaoting","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixue","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohe","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyue","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conglu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honggang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Ai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0119137","DOI":"10.1371\/journal.pone.0119137","article-title":"Chemoprotective effect of taurine on potassium bromate-induced DNA damage, DNA-protein cross-linking and oxidative stress in rat intestine.","volume":"10","author":"Ahmad","year":"2015","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1007\/s00726-017-2467-5","article-title":"The effect of aspartate supplementation on the microbial composition and innate immunity on mice.","volume":"49","author":"Bin","year":"2017","journal-title":"Amino Acids"},{"key":"B3","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1111\/nmo.12795","article-title":"Electrophysiological and morphological changes in colonic myenteric neurons from chemotherapy-treated patients: A pilot study.","volume":"28","author":"Carbone","year":"2016","journal-title":"Neurogastroenterol. 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