Probiotics: insights and new opportunities for Clostridioides difficile intervention

Rusha Pal¹, Ahmad I M Athamneh², Riddhi Deshpande³, Jose A R Ramirez⁴, Kayode T Adu^{4

5}, Pushpanathan Muthuirulan⁶, Shrikant Pawar⁷, Manuele Biazzo⁸, Yiorgos Apidianakis⁹, Ulrik Kraemer Sundekilde¹⁰, Cesar de la Fuente-Nunez^{11

12

13}, Mark G Martens^{3

14}, George P Tegos¹⁴, Mohamed N Seleem^{1

15}

Affiliations

¹ Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
² Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
³ Reading Hospital, Tower Health, West Reading, PA, USA.
⁴ ProbioWorld Consulting Group, James Cook University, Queensland, Australia.
⁵ Cann Group, Walter and Eliza Hall Institute, La Trobe University, Victoria, Australia.
⁶ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
⁷ The Anlyan Center Yale Center for Genomic Analysis, Yale School of Medicine, New Haven, CT, USA.
⁸ The Bioarte Ltd Laboratories at Life Science Park, San Gwann, Malta.
⁹ Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
¹⁰ Department of Food Science, Aarhus University, Aarhus, Denmark.
¹¹ Departments of Psychiatry and Microbiology, Machine Biology Group, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹² Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.
¹³ Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA, USA.
¹⁴ Drexel University College of Medicine, Philadelphia, PA, USA.
¹⁵ Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.

PMID: 35574602
PMCID: PMC9743071
DOI: 10.1080/1040841X.2022.2072705

Review

Probiotics: insights and new opportunities for Clostridioides difficile intervention

Rusha Pal et al. Crit Rev Microbiol. 2023 May.

. 2023 May;49(3):414-434.

doi: 10.1080/1040841X.2022.2072705. Epub 2022 May 15.

Authors

Affiliations

¹ Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
² Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
³ Reading Hospital, Tower Health, West Reading, PA, USA.
⁴ ProbioWorld Consulting Group, James Cook University, Queensland, Australia.
⁵ Cann Group, Walter and Eliza Hall Institute, La Trobe University, Victoria, Australia.
⁶ Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
⁷ The Anlyan Center Yale Center for Genomic Analysis, Yale School of Medicine, New Haven, CT, USA.
⁸ The Bioarte Ltd Laboratories at Life Science Park, San Gwann, Malta.
⁹ Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
¹⁰ Department of Food Science, Aarhus University, Aarhus, Denmark.
¹¹ Departments of Psychiatry and Microbiology, Machine Biology Group, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹² Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.
¹³ Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA, USA.
¹⁴ Drexel University College of Medicine, Philadelphia, PA, USA.
¹⁵ Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.

PMID: 35574602
PMCID: PMC9743071
DOI: 10.1080/1040841X.2022.2072705

Abstract

Clostridioides difficile infection (CDI) is a life-threatening disease caused by the Gram-positive, opportunistic intestinal pathogen C. difficile. Despite the availability of antimicrobial drugs to treat CDI, such as vancomycin, metronidazole, and fidaxomicin, recurrence of infection remains a significant clinical challenge. The use of live commensal microorganisms, or probiotics, is one of the most investigated non-antibiotic therapeutic options to balance gastrointestinal (GI) microbiota and subsequently tackle dysbiosis. In this review, we will discuss major commensal probiotic strains that have the potential to prevent and/or treat CDI and its recurrence, reassess the efficacy of probiotics supplementation as a CDI intervention, delve into lessons learned from probiotic modulation of the immune system, explore avenues like genome-scale metabolic network reconstructions, genome sequencing, and multi-omics to identify novel strains and understand their functionality, and discuss the current regulatory framework, challenges, and future directions.

Keywords: C. difficile; Probiotics; discovery informatics; genomic exploration; immunomodulatory; inhibition; metabolomics; multi-omics; regulatory requirements; virulence.

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Conflict of interest statement

Disclosure statement: The authors report no competing interest.

Figures

**Fig.1:**
Schematic depiction of the effect of probiotics in the context of treating/preventing CDI. Probiotics can have several effects that can be useful for treating/preventing *C. difficile* including competition for nutrients, resulting in inhibition of pathogen outgrowth through conversion of bile acids, improved barrier function, abundance of microbiome, and modulation of the immune system. Probiotics an also play a potential role in inhibition of *C. difficile* virulence factors (toxins and spores).

See this image and copyright information in PMC

References

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Probiotics: insights and new opportunities for Clostridioides difficile intervention

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Probiotics: insights and new opportunities for Clostridioides difficile intervention

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Conflict of interest statement

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