A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection
| Autor: | Jamie Hughes, Tanya Monaghan, Yingrui Li, Christopher Wang, Minkun Wang, Christos Polytarchou, Tung on Yau, Lindsey Russell, Maria Hatziapostolou, David Y. Yang, Jesus Miguens Blanco, Ruth Griffin, Karen Wong, Dina Kao, Niki Christodoulou, Andre Franke, Lynora Saxinger, Gordan Lauc, Julian Marchesi, Elisa Rosati, Paddy Tighe, Brandi Roach, Frano Vučković, Gane Ka-Shu Wong, Maja Pučić-Baković, Benjamin H. Mullish, Tania Dottorini, Animesh Acharjee, Julie A. K. McDonald, Filip Klicek, Niharika A. Duggal, Ning Xue |
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| Přispěvatelé: | Imperial College Healthcare NHS Trust- BRC Funding |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
genetic structures
QH301-705.5 Systems biology SOFTWARE Gut flora host-microbial interactions digestive system DISEASE Clostridioides difficile fluids and secretions Immunophenotyping Immune system Phenomics MEMORY B-CELLS EPIDEMIOLOGY FIBROSIS Medicine RECURRENT Biology (General) Epigenomics immunosenescence Science & Technology biology business.industry GUT MICROBIOTA fecal microbiota transplantation systems biology Cell Biology General Medicine Immunosenescence biology.organism_classification stomatognathic diseases surgical procedures operative RESOLUTION ANTIBODIES Immunology Observational study HEALTH systems biology 1. Introduction business Life Sciences & Biomedicine |
| Zdroj: | Cells, Vol 10, Iss 3234, p 3234 (2021) Cells Volume 10 Issue 11 |
| ISSN: | 2073-4409 |
| Popis: | Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI) increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies. |
| Databáze: | OpenAIRE |
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