Trends Mol Med. 2024 Mar;30(3):209-222. doi: 10.1016/j.molmed.2023.12.005.Epub 2024 Jan 8.

Catherine M Andary ¹, Kait F Al ², John A Chmiel ², Shaeley Gibbons ², Brendan A Daisley ³, Seema Nair Parvathy ⁴, Saman Maleki Vareki ⁵, Dawn M E Bowdish ⁶, Michael S Silverman ⁷, Jeremy P Burton ⁸

Author information

¹Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.

²Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Canadian Centre for Human Microbiome and Probiotics Research, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada.

³Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.

⁴Division of Infectious Disease, St. Joseph's Health Care, London, Ontario, Canada.

⁵Lawson Health Research Institute, London, Ontario, Canada; Department of Oncology, Western University, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.

⁶Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; McMaster Immunology Research Centre and the Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada.

⁷Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada; Division of Infectious Disease, St. Joseph's Health Care, London, Ontario, Canada.

⁸Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Canadian Centre for Human Microbiome and Probiotics Research, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada; Department of Surgery, Western University, London, Ontario, Canada. Electronic address: jeremy.burton@lawsonresearch.com.

Abstract

Fecal microbiota transplantation (FMT) has emerged as an alternative or adjunct experimental therapy for microbiome-associated diseases following its success in the treatment of recurrent Clostridioides difficile infections (rCDIs). However, the mechanisms of action involved remain relatively unknown. The term 'dysbiosis' has been used to describe microbial imbalances in relation to disease, but this traditional definition fails to consider the complex cross-feeding networks that define the stability of the microbiome. Emerging research transitions toward the targeted restoration of microbial functional networks in treating different diseases. In this review, we explore potential mechanisms responsible for the efficacy of FMT and future therapeutic applications, while revisiting definitions of 'dysbiosis' in favor of functional network restoration in rCDI, inflammatory bowel diseases (IBDs), metabolic diseases, and cancer.