Faecalibacterium prausnitzii and a Prebiotic Protect Intestinal Health in a Mouse Model of Antibiotic and Clostridium difficile Exposure

JPEN J Parenter Enteral Nutr. 2018 Sep;42(7):1156-1167. doi: 10.1002/jpen.1053. Epub 2018 Jan 31.

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.

Keywords: antibiotics; butyrate, Clostridium difficile, innate immunity, intestine, microbiome, prebiotic, probiotics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anion Transport Proteins / metabolism
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Butyrates / metabolism
  • Butyrates / pharmacology
  • Clindamycin / adverse effects
  • Clostridioides difficile / drug effects
  • Clostridioides difficile / growth & development*
  • Clostridioides difficile / metabolism
  • Clostridioides difficile / pathogenicity
  • Clostridium Infections / drug therapy*
  • Clostridium Infections / immunology
  • Clostridium Infections / metabolism
  • Clostridium Infections / microbiology
  • Colon / drug effects
  • Colon / metabolism
  • Colon / microbiology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dysbiosis / etiology
  • Faecalibacterium prausnitzii* / growth & development
  • Faecalibacterium prausnitzii* / metabolism
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome* / drug effects
  • Immunity, Innate / drug effects
  • Prebiotics*
  • Probiotics / therapeutic use*
  • Rats, Sprague-Dawley
  • Receptors, Immunologic / metabolism
  • Solanum tuberosum / chemistry
  • Starch / pharmacology
  • Starch / therapeutic use
  • Tight Junction Proteins / metabolism

Substances

  • Anion Transport Proteins
  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Butyrates
  • Clostridium difficile enterotoxin B receptor
  • Cytokines
  • Prebiotics
  • Receptors, Immunologic
  • Tight Junction Proteins
  • Clindamycin
  • Starch