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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Infectious Agents and Disease

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1555220

Non-invasive treatment of Clostridioides difficile infection with a human-origin probiotic cocktail through gut microbiome-gut metabolome modulations

Provisionally accepted
  • 1 Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, United States
  • 2 Department Of Biomedical And Chemical Engineering And Sciences, College Of Engineering And Science, Florida Institute of Technology, Melbourne, Florida, United States
  • 3 Ohio University, Athens, United States

The final, formatted version of the article will be published soon.

    Clostridioides difficile (C. difficile) is a leading cause of hospital-associated diarrhea, primarily due to gut dysbiosis following antibiotic use. Probiotics have been found to provide several benefits to hosts via modulation of the gut microbiota and their metabolites. However, till now, no conventional probiotics have been clearly proven to be an effective prophylactic option for CDI prevention. Therefore, more studies on developing specific probiotic candidates targeting CDI and improving diversity of probiotics administrated are needed. In this study, a humanorigin highly diverse and highly targeted probiotic cocktail (Pro11) containing 11 various probiotic species was developed against C. difficile. Pro11 protected mice against CDI with lower clinical scores and higher survival rates, and inhibited C. difficile in vivo with less C. difficile burden and toxins production determined in colon. Histological analysis demonstrated that Pro11 strengthened gut barrier, reducing gut permeability (less secreted sCD14 in serum) and gut inflammation. In addition, gut microbiome analysis demonstrated that Pro11 increased gut microbiome diversity and beneficial species. Along with gut microbiome modulation, gut metabolites including butyrate, were significantly increased in the probiotics-fed group. Results from this study highlighted probiotics as a promising CDI therapy as gut microbiota modulators, which will lay the foundation for translating probiotics in mitigating CDI and other intestinal pathogens for clinical use.

    Keywords: hospital-associated diarrhea, Clostridioides difficile, Probiotics, gut microbiome, gut metabolites

    Received: 03 Jan 2025; Accepted: 10 Feb 2025.

    Copyright: © 2025 Gurung, Courreges, Wang, Malgor and Wang. 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: Shaohua Wang, Ohio University, Athens, United States

    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.

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