ORIGINAL RESEARCH article
Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 13 - 2025 | doi: 10.3389/fchem.2025.1635781
This article is part of the Research TopicMedicinal and edible TCMs: Extraction and Isolation, Structural Elucidation, Pharmacological Evaluation, Structural Modification, and Quality ControlView all 9 articles
Preclinical evaluation of 6-Gingerol in modulating gut microbiota and SCFAs to mitigate Clostridium difficile-associated diarrhea in mice
Provisionally accepted
- 1Beijing Ditan Hospital, Capital Medical University, Beijing, China
- 2Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
- 3Yunnan University of Chinese Medicine, Kunming, China
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Clostridium difficile-associated diarrhea (CDAD) is a growing healthcare concern with limited effective treatments. 6-Gingerol, a major bioactive compound in ginger, exhibits notable antibacterial and anti-inflammatory properties, making it a potential alternative therapy. This study combines in vitro and in vivo approaches to evaluate its efficacy against CDAD. In vitro assays determined the half-maximal inhibitory concentration (IC₅₀) and minimum inhibitory concentration (MIC) of 6-Gingerol against C. difficile, which were 61.99 μM and 173.3 μM, respectively, indicating direct antibacterial activity. In vivo, a mouse model of CDAD was used to assess the therapeutic effects of 6-Gingerol. Outcomes included clinical symptoms, C. difficile load, inflammation, intestinal barrier integrity, gut microbiota composition, and short-chain fatty acids (SCFAs) levels. The results showed that in the CDAD mouse model, high-dose 6-Gingerol significantly alleviated CDAD symptoms, reduced C. difficile load (P<0.001), improved gut barrier function, and suppressed intestinal inflammation. Although it did not notably increase microbial diversity, 6-Gingerol modulated gut microbiota structure—markedly increasing beneficial bacteria such as Lactobacillus acidophilus (P<0.01) and Bacteroides thetaiotaomicron, while reducing harmful bacteria including Klebsiella pneumoniae and Proteus mirabilis. Targeted quantification revealed restored levels of key SCFAs, particularly acetate (P<0.001), butyrate (P<0.01), and valerate (P<0.001), which are closely linked to gut health and recovery from CDAD. In summary, 6-Gingerol exerts therapeutic effects against CDAD through direct inhibition of C. difficile, regulation of gut microbiota, restoration of SCFA levels, and protection of the intestinal barrier, highlighting its potential as a novel natural treatment for CDAD.
Keywords: ：6-Gingerol, Clostridium difficile-associated diarrhea, Pharmacodynamic evaluation, Gut Microbiota, Short-chain fatty acids (SCFAs)
Received: 27 May 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Ma, Zhu, Li, Yu, Tang, Zhang and Ma. 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:
Cong-En Zhang, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
Zhijie Ma, Beijing Ditan Hospital, Capital Medical University, Beijing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.