Fecal microbiota transplantation: current challenges and future landscapes

Yadegar, Abbas; Bar-Yoseph, Haggai; Monaghan, Tanya Marie; Severino, Andrea; Pakpour, Sepideh; Kuijper, Ed J.; Smits, Wiep Klaas; Terveer, Elisabeth M.; Neupane, Sukanya; Nabavi-Rad, Ali; Sadeghi, Javad; Cammarota, Giovanni; Ianiro, Gianluca; Nap-Hill, Estello; Leung, Dickson; Wong, Karen; Kao, Dina

Abstract

Given the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main “whole gut microbiome replacement” strategy and has been integrated into clinical practice guidelines for treating recurrent Clostridioides difficile infection (rCDI). Furthermore, the potential application of FMT in other indications such as inflammatory bowel disease, metabolic syndrome, and solid tumor malignancies is an area of intense interest and active research. However, the complex and variable nature of FMT makes it challenging to address its precise functionality and to assess clinical efficacy and safety in different disease contexts.
In this review, we will outline clinical applications, efficacy, durability, and safety of FMT and will provide a comprehensive assessment of its procedural and administratiion aspects. The clinical applications of FMT in children and cancer immunotherapy are also described. We will focus on data from human studies in inflammatory bowel disease (IBD) in contrast with rCDI to delineate the putative mechanisms of this treatment in IBD as a model, including colonization resistance and functional restoration through bacterial engraftment, modulating effects of virome/phageome, gut metabolome and host interactions, and immunoregulatory actions of FMT. Furthermore, we will comprehensively review omics technologies, metagenomic approaches, and bioinformatics pipelines to characterize complex microbial communities and discuss their limitations. FMT regulatory challenges, ethical considerations, and pharmacomicrobiomics are also highlighted to shed light on future development of tailored microbiome-based therapeutics.

Citation

Yadegar, A., Bar-Yoseph, H., Monaghan, T. M., Severino, A., Pakpour, S., Kuijper, E. J., Smits, W. K., Terveer, E. M., Neupane, S., Nabavi-Rad, A., Sadeghi, J., Cammarota, G., Ianiro, G., Nap-Hill, E., Leung, D., Wong, K., & Kao, D. (2024). Fecal microbiota transplantation: current challenges and future landscapes. Clinical Microbiology Reviews, 37(2), Article e00060-22. https://doi.org/10.1128/cmr.00060-22

• Journal Article Type: Review
• Acceptance Date: Apr 6, 2024
• Online Publication Date: May 8, 2024
• Publication Date: 2024-06
• Deposit Date: Apr 7, 2024
• Publicly Available Date: Jun 17, 2024
• Journal: Clinical Microbiology Reviews
• Print ISSN: 0893-8512
• Electronic ISSN: 1098-6618
• Publisher: American Society for Microbiology
• Peer Reviewed: Peer Reviewed
• Volume: 37
• Issue: 2
• Article Number: e00060-22
• DOI: https://doi.org/10.1128/cmr.00060-22
• Keywords: fecal microbiota transplantation, human microbiome, Clostridioides difficile infection, microbial engraftment, donor screening
• Public URL: https://nottingham-repository.worktribe.com/output/33490320
• Publisher URL: https://journals.asm.org/doi/10.1128/cmr.00060-22