4.6 Article

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

期刊

CELLS
卷 10, 期 11, 页码 -

出版社

MDPI
DOI: 10.3390/cells10113234

关键词

fecal microbiota transplantation; Clostridioides difficile; immunosenescence; host-microbial interactions; systems biology

资金

  1. University of Nottingham Research Priority Area grant
  2. National Institute for Health Research (NIHR) Nottingham Digestive Diseases Biomedical Research Centre at Nottingham University Hospitals NHS Trust and University of Nottingham
  3. Litwin Initiative, Crohns and Colitis Foundation
  4. NTU Quality Research (QR) funds
  5. DFG [409096610003]
  6. DFG Excellence Cluster Precision Medicine in Chronic Inflammation [Exc2167]
  7. Alberta Health Services and University of Alberta Hospital Foundation
  8. Medical Research Council (MRC) Clinical Research Training Fellowship [MR/R000875/1]
  9. NIHR Academic Clinical Lectureship [CL-2019-21-002]
  10. MRC [MC_PC_12025]
  11. NIHR [MC_PC_12025]
  12. European Structural and Investment Funds [CEKOM KK.01.2.2.03.0006]
  13. IRI grant [KK.01.2.1.01.0003]
  14. Croatian National Centre of Research Excellence in Personalized Healthcare grant [KK.01.1.1.01.0010]
  15. Merck

向作者/读者索取更多资源

Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridioides difficile infection, and new evidence suggests its potential in severe cases. A deep phenomics study conducted on four adults undergoing sequential FMT for severe infection revealed differences in host responses, suggesting immunosenescent signals in non-responders. Further research with larger sample sizes is needed to validate these preliminary findings on the mechanisms of successful FMT.
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.

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