Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection
| Autor: | Mullish, Benjamin H., McDonald, Julie A. K., Pechlivanis, Alexandros, Allegretti, Jessica R., Kao, Dina, Barker, Grace F., Kapila, Diya, Petrof, Elaine O., Joyce, Susan A., Gahan, Cormac G., Glegola-Madejska, Izabela, Williams, Horace R. T., Holmes, Elaine, Clarke, Thomas B., Thursz, Mark R., Marchesi, Julian R. |
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| Přispěvatelé: | Medical Research Council, Medical Research Council (MRC), Imperial College London Joint Translational Fund, Imperial College Healthcare NHS Trust- BRC Funding, Wellcome Trust, Imperial College Healthcare NHS Trust: Research Capability Funding (RCF) |
| Rok vydání: | 2019 |
| Předmět: |
DNA
Bacterial COLONOSCOPY METABOLISM Amidohydrolases Mice Recurrence Tandem Mass Spectrometry Animals Humans Faecal microbiota transplant (FMT) bile acids Science & Technology Gastroenterology & Hepatology gut microbiota metabonome Clostridioides difficile STRAINS 1103 Clinical Sciences SPORE GERMINATION Fecal Microbiota Transplantation Gastrointestinal Microbiome Mice Inbred C57BL Bile salt hydrolases (BSHs) Disease Models Animal SCINDENS ACID Clostridium Infections Recurrent Clostridioides difficile infection (rCDI) bile salt hydrolase 1114 Paediatrics and Reproductive Medicine Female Life Sciences & Biomedicine Glycocholic Acid |
| ISSN: | 0017-5749 |
| Popis: | 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.\ud \ud \ud 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.\ud \ud \ud 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 |
| Databáze: | OpenAIRE |
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