Fecal Microbiota Transplantation Across the Lifespan: Balancing Efficacy, Safety, and Innovation

Introduction

The gut microbiota represents the community of microbes that live within our gastrointestinal tract. Composed of bacteria, viruses, fungi, protozoa, and archaea, these organisms play a key role in human health and disease. Unhealthy disruptions of the gutmicrobiota result in enteric dysbiosis,which has been implicated in several disorders, from inflammatory bowel disease (IBD) to metabolic syndrome (1,2). This has led physicians and researchers to search for therapeutic approaches to restore microbial health and homeostasis.

The necessity for a restorative approach has becomemore urgentwith the rising incidence of Clostridioides difficile infections (CDI) over the past 2 decades. In many cases, vulnerability to CDI results from exposure to antibiotics that drive enteric dysbiosis. This impairs colonization resistance, which is the ability of the microbiota to inhibit colonization by C. difficile (3). Moreover, classical antibiotic treatments to treat CDI can perpetuate injury to the gutmicrobiota.This sets the stage for recurrent C. difficile infections (rCDI), which occur in 20%–30% of patients (4). Fecalmicrobiota transplantation (FMT) emerged largely in response to this challenge and has been shown to repair antibiotic injury and restore colonization resistance to C. difficile (5).

FMT involves the delivery of a stool microbiota from a healthy individual to a patient, with the goal of restoring a healthy microbial community in the gut. The US Food and Drug Administration(FDA) currently maintains a policy of enforcementdiscretion, which allows FMT to be used solely for the treatment of CDI not responsive to standard therapies, without requiring an investigational new drug application (6). This 2013 policy has given clinicians a reprieve from the burden of regulatory paperwork associated with an investigational new drug and has givenpatients with CDI access to FMT treatment. Through this review, we hope to update clinicians, researchers, and regulators on the efficacy, safety, and innovation of FMT, with an emphasis on how these factors must be balanced across the lifespan (Table 1).