Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection.

Gut
Benjamin H MullishJulian R Marchesi

Abstract

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. 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. 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 p...Continue Reading

References

Jun 1, 2000·Applied and Environmental Microbiology·H TanakaI Mierau
Apr 15, 2003·Clinica Chimica Acta; International Journal of Clinical Chemistry·James E WellsPhillip B Hylemon
Nov 22, 2005·Journal of Lipid Research·Jason M RidlonPhillip B Hylemon
Feb 5, 2008·Journal of Bacteriology·Joseph A Sorg, Abraham L Sonenshein
Sep 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Brian V JonesJulian R Marchesi
Sep 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jonathan R SwannElaine Holmes
Nov 29, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Alexa R WeingardenAlexander Khoruts
May 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Susan A JoyceCormac G M Gahan
Nov 21, 2015·BMJ : British Medical Journal·Benjamin H Mullish, Horace R T Williams
Apr 19, 2016·Alimentary Pharmacology & Therapeutics·J R AllegrettiJ R Korzenik
Oct 13, 2017·International Journal for Quality in Health Care : Journal of the International Society for Quality in Health Care·Alice KingPaul Aylin
Apr 29, 2018·Methods : a Companion to Methods in Enzymology·Benjamin H MullishJulie A K McDonald

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Citations

Sep 17, 2020·Clinical Medicine : Journal of the Royal College of Physicians of London·Charlotte WoodhouseVishal C Patel
Sep 22, 2020·Future Microbiology·Gianluca IaniroGiovanni Cammarota
Aug 19, 2020·Journal of Crohn's & Colitis·Scott W Olesen, Ylaine Gerardin
Mar 7, 2019·Nature Reviews. Gastroenterology & Hepatology·Clemens Thoma
Jul 1, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Xi QianCheleste M Thorpe
Jan 11, 2020·Frontiers in Microbiology·Xianping LiZhihong Ren
Apr 17, 2020·AAPS PharmSciTech·Hala M Fadda
Mar 5, 2020·BMC Microbiology·Thierry ChénardEric Massé
Jul 6, 2020·Nature Communications·Yandong XiaoYang-Yu Liu
Sep 22, 2020·Therapeutic Advances in Gastroenterology·Jonathan P SegalHarry Sokol
Feb 13, 2020·F1000Research·Eamonn M M Quigley, Prianka Gajula
Aug 28, 2020·Nature Reviews. Gastroenterology & Hepatology·Alexander KhorutsMichael J Sadowsky
Jul 15, 2020·Critical Care : the Official Journal of the Critical Care Forum·Daosheng WangYibing Peng
May 28, 2020·International Journal of Molecular Sciences·Pamela VernocchiLorenza Putignani
Feb 27, 2020·Cell Host & Microbe·Sidhartha R SinhaAida Habtezion
Mar 26, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Zi-Wei YuHui-Ling Hu
Mar 23, 2021·Therapeutic Advances in Gastroenterology·Kanika Sehgal, Sahil Khanna
Apr 4, 2021·International Journal of Molecular Sciences·Negin KazemianSepideh Pakpour
Apr 4, 2021·Microorganisms·Jack W DalyCormac G M Gahan
Apr 17, 2021·Environmental Science and Pollution Research International·Amr El-SayedMohamed Kamel
Apr 29, 2021·Nature Reviews. Gastroenterology & Hepatology·Camille DanneHarry Sokol

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Methods Mentioned

BETA
chip
bile acid profiling
bile
PCA

Software Mentioned

rCCA
DA
Piphillin
OPLS

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Bacteriotherapy, also known as fecal transplantation, involves the transfer of stool from a healthy donor into the gastrointestinal tract for the purpose of treating recurrent C. difficile colitis. Here is the latest on bacteriotherapy.

Bacteriotherapy

Bacteriotherapy, also known as fecal transplantation, involves the transfer of stool from a healthy donor into the gastrointestinal tract for the purpose of treating recurrent C. difficile colitis. Here is the latest on bacteriotherapy.