Sanjoy Roychowdhury1, Jennifer Cadnum2, Bryan Glueck1, Mark Obrenovich2, Curtis Donskey2,3, Gail A M Cresci1,4,5. 1. Lerner Research Institute, Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio, USA. 2. Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA. 3. Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio, USA. 4. Pediatric Institute, Department of Gastroenterology, Cleveland Clinic, Cleveland, Ohio, USA. 5. Digestive Disease & Surgery Institute, Department of Gastroenterology & Hepatology, Cleveland Clinic, Cleveland, Ohio, USA.
Abstract
BACKGROUND: Clostridium difficile (CD) infection (CDI) increases patient morbidity, mortality and healthcare costs. Antibiotic treatment induces gut dysbiosis and is both a major risk factor for CD colonization and treatment of CDI. Probiotics have been trialed to support commensal gut microbiota and reduce CDI. This study investigated commensal microbe Faecalibacterium prausnitzii (FP) and a prebiotic, both known to yield butyrate and be anti-inflammatory and immunomodulatory, on CD colonization and gut integrity in mice. METHODS: Mice were randomly grouped and supplemented daily with FP, prebiotic, FP + prebiotic, FP/prebiotic supernatant, or saline throughout the entire study. Following treatment with clindamycin for 3 days, mice were exposed to CD. Feces were collected at baseline, the day after antibiotic, and 1, 3, and 5 days after CD exposure and cultured for bacterial overgrowth and CD colonization. On days 1 and 5 after CD exposure, mice were randomly euthanized, and proximal colon was dissected for histological analysis and preparation of RNA for analysis of proinflammatory and anti-inflammatory cytokines. RESULTS: Although all mice exhibited bacterial overgrowth and CD colonization, bacterial burden resolved quicker in the FP + prebiotic group. This was associated with induction and resolution of innate immune responses, anion exchanger, and tight junction protein preservation in proximal colon. CD toxin virulence potential was questionable as expression of CD toxin B receptor was depleted in the FP + prebiotic group. CONCLUSION: Supplementation with anti-inflammatory butyrate-supporting commensal bacteria and prebiotic may support innate immune responses and minimize bacterial burden and negative effects during antibiotic and CD exposure.
BACKGROUND:Clostridium difficile (CD) infection (CDI) increases patient morbidity, mortality and healthcare costs. Antibiotic treatment induces gutdysbiosis and is both a major risk factor for CD colonization and treatment of CDI. Probiotics have been trialed to support commensal gut microbiota and reduce CDI. This study investigated commensal microbe Faecalibacterium prausnitzii (FP) and a prebiotic, both known to yield butyrate and be anti-inflammatory and immunomodulatory, on CD colonization and gut integrity in mice. METHODS:Mice were randomly grouped and supplemented daily with FP, prebiotic, FP + prebiotic, FP/prebiotic supernatant, or saline throughout the entire study. Following treatment with clindamycin for 3 days, mice were exposed to CD. Feces were collected at baseline, the day after antibiotic, and 1, 3, and 5 days after CD exposure and cultured for bacterial overgrowth and CD colonization. On days 1 and 5 after CD exposure, mice were randomly euthanized, and proximal colon was dissected for histological analysis and preparation of RNA for analysis of proinflammatory and anti-inflammatory cytokines. RESULTS: Although all mice exhibited bacterial overgrowth and CD colonization, bacterial burden resolved quicker in the FP + prebiotic group. This was associated with induction and resolution of innate immune responses, anion exchanger, and tight junction protein preservation in proximal colon. CD toxin virulence potential was questionable as expression of CD toxin B receptor was depleted in the FP + prebiotic group. CONCLUSION: Supplementation with anti-inflammatory butyrate-supporting commensal bacteria and prebiotic may support innate immune responses and minimize bacterial burden and negative effects during antibiotic and CD exposure.
Authors: Susan E Pryde; Sylvia H Duncan; Georgina L Hold; Colin S Stewart; Harry J Flint Journal: FEMS Microbiol Lett Date: 2002-12-17 Impact factor: 2.742
Authors: Colin Hill; Francisco Guarner; Gregor Reid; Glenn R Gibson; Daniel J Merenstein; Bruno Pot; Lorenzo Morelli; Roberto Berni Canani; Harry J Flint; Seppo Salminen; Philip C Calder; Mary Ellen Sanders Journal: Nat Rev Gastroenterol Hepatol Date: 2014-06-10 Impact factor: 46.802
Authors: Lawrence J Brandt; Olga C Aroniadis; Mark Mellow; Amy Kanatzar; Colleen Kelly; Tina Park; Neil Stollman; Faith Rohlke; Christina Surawicz Journal: Am J Gastroenterol Date: 2012-03-27 Impact factor: 10.864
Authors: Melinda A Engevik; Kristen A Engevik; Mary Beth Yacyshyn; Jiang Wang; Daniel J Hassett; Benjamin Darien; Bruce R Yacyshyn; Roger T Worrell Journal: Am J Physiol Gastrointest Liver Physiol Date: 2014-12-31 Impact factor: 4.052
Authors: Christopher Staley; Colleen R Kelly; Lawrence J Brandt; Alexander Khoruts; Michael J Sadowsky Journal: MBio Date: 2016-12-20 Impact factor: 7.867
Authors: Mark Obrenovich; Hayden Jaworski; Tara Tadimalla; Adil Mistry; Lorraine Sykes; George Perry; Robert A Bonomo Journal: Microorganisms Date: 2020-05-23
Authors: Anthony M Buckley; Ines B Moura; Norie Arai; William Spittal; Emma Clark; Yoshihiro Nishida; Hannah C Harris; Karen Bentley; Georgina Davis; Dapeng Wang; Suparna Mitra; Takanobu Higashiyama; Mark H Wilcox Journal: Front Cell Infect Microbiol Date: 2021-07-02 Impact factor: 5.293