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

Autori
Monaghan, Tanya M. ; Duggal, Niharika A. ; Rosati, Elisa ; Griffin, Ruth ; Hughes, Jamie ; Roach, Brandi ; Yang, David Y. ; Wang, Christopher ; Wong, Karen ; Saxinger, Lynora ; Pučić-Baković, Maja ; Vučković, Frano ; Klicek, Filip ; Lauc, Gordan ; Tighe, Paddy ; Mullish, Benjamin H. ; Blanco, Jesus Miguens ; McDonald, Julie A. K. ; Marchesi, Julian R. ; Xue, Ning ; Dottorini, Tania ; Acharjee, Animesh ; Franke, Andre ; Li, Yingrui ; Wong, Gane Ka-Shu ; Polytarchou, Christos ; Yau, Tung On ; Christodoulou, Niki ; Hatziapostolou, Maria ; Wang, Minkun ; Russell, Lindsey A. ; Kao, Dina H.

Izvornik
Cells (2073-4409) 10 (2021), 11; 3234, 24

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
fecal microbiota transplantation ; Clostridioides difficile ; immunosenescence ; host-microbial interactions ; systems biology 1. Introduction

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA