Imperial College London

Dr Benjamin Mullish

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

NIHR Clinical Lecturer
 
 
 
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Contact

 

b.mullish

 
 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mullish:2019:10.1136/gutjnl-2018-317842,
author = {Mullish, BH and McDonald, JAK and Pechlivanis, A and Allegretti, JR and Kao, D and Barker, GF and Kapila, D and Petrof, EO and Joyce, SA and Gahan, CGM and Glegola-Madejska, I and Williams, HRT and Holmes, E and Clarke, TB and Thursz, MR and Marchesi, JR},
doi = {10.1136/gutjnl-2018-317842},
journal = {Gut},
pages = {1791--1800},
title = {Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection},
url = {http://dx.doi.org/10.1136/gutjnl-2018-317842},
volume = {68},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Objective Faecal microbiota transplant (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect C. difficile germination or vegetative growth. We hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT’s efficacy in treating the condition.Design Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of bsh/baiCD genes involved in bile metabolism. Human data were validated in C. difficile batch cultures and a C57BL/6 mouse model of rCDI.Results From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent C. difficile germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and bsh/baiCD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered bsh-expressing E. coli and naturally BSH-producing organisms (Bacteroides ovatus, Collinsella aerofaciens, Bacteroides vulgatus and Blautia obeum) reduced TCA-mediated C. difficile germination relative to culture supernatant of wild-type (BSH-negative) E. coli. C. difficile total viable counts were ~70% reduced in an rCDI mouse model after administration of E. coli expressing highly active BSH relative to mice administered BSH-negative E. coli (p<0.05).Conclusion Restoration of gut BSH functionality contributes to the efficacy of FMT in treating rCDI.
AU - Mullish,BH
AU - McDonald,JAK
AU - Pechlivanis,A
AU - Allegretti,JR
AU - Kao,D
AU - Barker,GF
AU - Kapila,D
AU - Petrof,EO
AU - Joyce,SA
AU - Gahan,CGM
AU - Glegola-Madejska,I
AU - Williams,HRT
AU - Holmes,E
AU - Clarke,TB
AU - Thursz,MR
AU - Marchesi,JR
DO - 10.1136/gutjnl-2018-317842
EP - 1800
PY - 2019///
SN - 0017-5749
SP - 1791
TI - Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection
T2 - Gut
UR - http://dx.doi.org/10.1136/gutjnl-2018-317842
UR - http://hdl.handle.net/10044/1/67139
VL - 68
ER -