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

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 unde...

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Autores principales:	Tanya M. Monaghan, 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 Miguens Blanco, Julie A. K. McDonald, Julian R. Marchesi, Ning Xue, Tania Dottorini, Animesh Acharjee, Andre Franke, Yingrui Li, Gane Ka-Shu Wong, Christos Polytarchou, Tung On Yau, Niki Christodoulou, Maria Hatziapostolou, Minkun Wang, Lindsey A. Russell, Dina H. Kao
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	fecal microbiota transplantation <i>Clostridioides difficile</i> immunosenescence host-microbial interactions systems biology Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7745900c03be42aca7c8715cf0961b52
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spelling	oai:doaj.org-article:7745900c03be42aca7c8715cf0961b522021-11-25T17:13:09ZA Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory <i>Clostridioides difficile</i> Infection10.3390/cells101132342073-4409https://doaj.org/article/7745900c03be42aca7c8715cf0961b522021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3234https://doaj.org/toc/2073-4409Fecal microbiota transplantation (FMT) is highly effective in recurrent <i>Clostridioides difficile</i> infection (CDI); increasing evidence supports FMT in severe or fulminant <i>Clostridioides difficile</i> 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.Tanya M. MonaghanNiharika A. DuggalElisa RosatiRuth GriffinJamie HughesBrandi RoachDavid Y. YangChristopher WangKaren WongLynora SaxingerMaja Pučić-BakovićFrano VučkovićFilip KlicekGordan LaucPaddy TigheBenjamin H. MullishJesus Miguens BlancoJulie A. K. McDonaldJulian R. MarchesiNing XueTania DottoriniAnimesh AcharjeeAndre FrankeYingrui LiGane Ka-Shu WongChristos PolytarchouTung On YauNiki ChristodoulouMaria HatziapostolouMinkun WangLindsey A. RussellDina H. KaoMDPI AGarticlefecal microbiota transplantation<i>Clostridioides difficile</i>immunosenescencehost-microbial interactionssystems biologyBiology (General)QH301-705.5ENCells, Vol 10, Iss 3234, p 3234 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fecal microbiota transplantation <i>Clostridioides difficile</i> immunosenescence host-microbial interactions systems biology Biology (General) QH301-705.5
spellingShingle	fecal microbiota transplantation <i>Clostridioides difficile</i> immunosenescence host-microbial interactions systems biology Biology (General) QH301-705.5 Tanya M. Monaghan 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 Miguens Blanco Julie A. K. McDonald Julian R. Marchesi Ning Xue Tania Dottorini Animesh Acharjee Andre Franke Yingrui Li Gane Ka-Shu Wong Christos Polytarchou Tung On Yau Niki Christodoulou Maria Hatziapostolou Minkun Wang Lindsey A. Russell Dina H. Kao A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory <i>Clostridioides difficile</i> Infection
description	Fecal microbiota transplantation (FMT) is highly effective in recurrent <i>Clostridioides difficile</i> infection (CDI); increasing evidence supports FMT in severe or fulminant <i>Clostridioides difficile</i> 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.
format	article
author	Tanya M. Monaghan 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 Miguens Blanco Julie A. K. McDonald Julian R. Marchesi Ning Xue Tania Dottorini Animesh Acharjee Andre Franke Yingrui Li Gane Ka-Shu Wong Christos Polytarchou Tung On Yau Niki Christodoulou Maria Hatziapostolou Minkun Wang Lindsey A. Russell Dina H. Kao
author_facet	Tanya M. Monaghan 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 Miguens Blanco Julie A. K. McDonald Julian R. Marchesi Ning Xue Tania Dottorini Animesh Acharjee Andre Franke Yingrui Li Gane Ka-Shu Wong Christos Polytarchou Tung On Yau Niki Christodoulou Maria Hatziapostolou Minkun Wang Lindsey A. Russell Dina H. Kao
author_sort	Tanya M. Monaghan
title	A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory <i>Clostridioides difficile</i> Infection
title_short	A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory <i>Clostridioides difficile</i> Infection
title_full	A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory <i>Clostridioides difficile</i> Infection
title_fullStr	A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory <i>Clostridioides difficile</i> Infection
title_full_unstemmed	A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory <i>Clostridioides difficile</i> Infection
title_sort	multi-factorial observational study on sequential fecal microbiota transplant in patients with medically refractory <i>clostridioides difficile</i> infection
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7745900c03be42aca7c8715cf0961b52
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A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory <i>Clostridioides difficile</i> Infection

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