Imperial College London
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Dr Benjamin Mullish

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

IPPRF Research Fellow
 
 
 
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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 <i>Clostridioides difficile</i> infection},
url = {http://dx.doi.org/10.1136/gutjnl-2018-317842},
volume = {68},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:sec><jats:title>Objective</jats:title><jats:p>Faecal microbiota transplant (FMT) effectively treats recurrent <jats:italic>Clostridioides difficile</jats:italic> infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect <jats:italic>C. difficile</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>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 <jats:italic>bsh</jats:italic>/<jats:italic>bai</jats:italic>CD genes involved in bile metabolism. Human data were validated in <jats:italic>C. difficile</jats:italic> batch cultures and a C57BL/6 mouse model of rCDI.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 <jats:italic>C. difficile</jats:italic> germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and <jats:italic>bsh</jats:italic>/<jats:italic>bai</jats:italic>CD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered <jats:italic>bsh</jats:italic>-expressing <jats:italic>E
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 <i>Clostridioides difficile</i> infection
T2  - Gut
UR  - http://dx.doi.org/10.1136/gutjnl-2018-317842
UR  - http://hdl.handle.net/10044/1/67139
VL  - 68
ER  -
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