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A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection

1
NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham NG7 2UH, UK
2
Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK
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MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK
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Institute of Clinical Molecular Biology, Universitätsklinikum Schleswig-Holstein, Christian-Albrecht University of Kiel, 24105 Kiel, Germany
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Synthetic Biology Research Centre, The University of Nottingham Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, UK
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Division of Gastroenterology, Department of Medicine, University of Alberta; Edmonton, Alberta, AB T6G 2G3, Canada
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Division of Infectious Diseases, Department of Medicine, University of Alberta; Edmonton, Alberta, AB T6G 2G3, Canada
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Glycoscience Research Laboratory, Genos Ltd., Borongajska cesta 83H, 10000 Zagreb, Croatia
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Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
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School of Life Sciences, University of Nottingham, Nottingham NG7 2RD, UK
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Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK
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MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK
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School of Veterinary Medicine and Science, University of Nottingham, Nottingham NG7 2UH, UK
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College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, Birmingham B15 2TT, UK
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Shenzhen Digital Life Institute, Shenzhen 518016, China
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Department of Biological Sciences, Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada
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Department of Biosciences, John van Geest Cancer Research Centre, Centre for Health Aging and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK
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Innovation Lab, Innovent Biologics, Inc., Suzhou 215011, China
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Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Walter Wahli and Pengfei Xu
Cells 2021, 10(11), 3234; https://doi.org/10.3390/cells10113234
Received: 16 October 2021 / Revised: 15 November 2021 / Accepted: 17 November 2021 / Published: 19 November 2021
(This article belongs to the Special Issue Gut Microbiota in Nutrition and Health)
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. View Full-Text
Keywords: fecal microbiota transplantation; Clostridioides difficile; immunosenescence; host-microbial interactions; systems biology fecal microbiota transplantation; Clostridioides difficile; immunosenescence; host-microbial interactions; systems biology
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MDPI and ACS Style

Monaghan, T.M.; Duggal, N.A.; Rosati, E.; Griffin, R.; Hughes, J.; Roach, B.; Yang, D.Y.; Wang, C.; Wong, K.; Saxinger, L.; Pučić-Baković, M.; Vučković, F.; Klicek, F.; Lauc, G.; Tighe, P.; Mullish, B.H.; Blanco, J.M.; McDonald, J.A.K.; Marchesi, J.R.; Xue, N.; Dottorini, T.; Acharjee, A.; Franke, A.; Li, Y.; Wong, G.K.-S.; Polytarchou, C.; Yau, T.O.; Christodoulou, N.; Hatziapostolou, M.; Wang, M.; Russell, L.A.; Kao, D.H. A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection. Cells 2021, 10, 3234. https://doi.org/10.3390/cells10113234

AMA Style

Monaghan TM, Duggal NA, Rosati E, Griffin R, Hughes J, Roach B, Yang DY, Wang C, Wong K, Saxinger L, Pučić-Baković M, Vučković F, Klicek F, Lauc G, Tighe P, Mullish BH, Blanco JM, McDonald JAK, Marchesi JR, Xue N, Dottorini T, Acharjee A, Franke A, Li Y, Wong GK-S, Polytarchou C, Yau TO, Christodoulou N, Hatziapostolou M, Wang M, Russell LA, Kao DH. A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection. Cells. 2021; 10(11):3234. https://doi.org/10.3390/cells10113234

Chicago/Turabian Style

Monaghan, Tanya M., Niharika A. Duggal, Elisa Rosati, Ruth Griffin, Jamie Hughes, Brandi Roach, David Y. Yang, Christopher Wang, Karen Wong, Lynora Saxinger, Maja Pučić-Baković, Frano Vučković, Filip Klicek, Gordan Lauc, Paddy Tighe, Benjamin H. Mullish, Jesus M. Blanco, Julie A.K. McDonald, Julian R. Marchesi, Ning Xue, Tania Dottorini, Animesh Acharjee, Andre Franke, Yingrui Li, Gane K.-S. Wong, Christos Polytarchou, Tung O. Yau, Niki Christodoulou, Maria Hatziapostolou, Minkun Wang, Lindsey A. Russell, and Dina H. Kao. 2021. "A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection" Cells 10, no. 11: 3234. https://doi.org/10.3390/cells10113234

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