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OC-063 Gut microbiota-host bile acid metabolism interactions in clostridium difficile infection: the explanation for the efficacy of faecal microbiota transplantation?
  1. BH Mullish1,
  2. JAK McDonald1,
  3. DH Kao2,
  4. JR Allegretti3,
  5. EO Petrof4,
  6. A Pechlivanis1,
  7. GF Barker1,
  8. SR Atkinson1,
  9. HRT Williams1,
  10. MR Thursz1,
  11. JR Marchesi1,5
  1. 1Centre for Digestive and Gut Health, Imperial College London, London, UK
  2. 2Division of Gastroenterology, University of Alberta, Edmonton, Canada
  3. 3Crohn’s and Colitis Centre, Brigham and Women’s Hospital, Massachusetts, USA
  4. 4Department of Medicine, Queen’s University, Kingston, Canada
  5. 5School of Biosciences, Cardiff University, Cardiff, UK

Abstract

Introduction Faecal microbiota transplantation (FMT) effectively treats recurrent Clostridium difficile infection (CDI), yet the mechanisms underlying its efficacy are poorly-defined. In vitro, conjugated primary bile salts (i.e. taurocholic acid) promote the germination of C. difficile, whilst secondary bile salts (i.e. deoxycholic acid) inhibit vegetative growth of the organism. As gut microbiota-derived enzymes (i.e. bile salt hydrolases (BSH)) are responsible for bile acid metabolism in vivo, we hypothesised that the efficacy of FMT may reflect transfer of BSH-producing bacteria, with restoration of a gut bile acid profile that inhibit germination/vegetative growth of C. difficile.

Method Faecal samples were collected from patients with recurrent CDI pre-FMT (n=26), at 8–12 weeks after successful FMT, and also from stool donors (n=17). Bacterial DNA was used for microbial profiling (via 16S rRNA gene sequencing) and for qPCR of BSH genes. Liquid chromatography-mass spectrometry was used for bile acid profiling. BSH enzyme activity was established using a plate-based precipitation assay.

Results Microbial and bile acid profiles from pre-FMT patients were markedly different to those found in the post-FMT and donor groups (p<0.001, PERMANOVA); qPCR confirmed enrichment of BSH-producing organisms post-FMT. Taurocholic acid levels were elevated (and deoxycholic acid levels reduced) pre-FMT compared to donors and post-FMT (p<0.001, Wilcoxon-Mann-Whitney test). By Spearman’s rank, abundance of BSH-producing bacteria negatively correlated with taurocholic acid and positively correlated with deoxycholic acid levels (Figure 1), with p<0.05 for this correlation for levels of both bile acids with Bacteroides vulgatus, Blautia obeum, Dorea longicatena, and Eubacterium rectale. Stool BSH activity was negligible pre-FMT, but was significantly increased post-FMT (p<0.002, Wilcoxon-Mann-Whitney).

Abstract OC-063 Figure 1

Heatmap demonstrating the correlation between abundance of BSH-secreting organisms and gut levels of taurocholic and deoxycholic acids (Spearman’s rank).

Conclusion The gut microbiota is enriched with BSH-producing bacterial species post-FMT for CDI, and these organisms are present within the gut microbiota of donors. The increased relative abundance of BSH-producing organisms post-FMT was negatively correlated with gut taurocholic acid levels, positively correlated with deoxycholic acid levels, and associated with increased BSH activity. These data collectively support a hypothesis of transfer of BSH-producing organisms during FMT linked to reconstitution of a gut bile acid profile unfavourable to the germination and growth of C. difficile.

Disclosure of Interest None Declared

  • clostridium difficile
  • Faecal Microbiota Transplant
  • gut microbiota
  • Microbiome

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