The impact of fecal microbiota transplantation on host immunity and epithelial restoration following Clostridioides difficile infection.

Fecal microbiota transplantation (FMT) has emerged as an effective therapy for the prevention of recurrent Clostridioides difficile infection (rCDI). Despite this therapeutic success, questions remain about safety and standardization of protocols, leading to calls for more defined biotherapeutics. While FMT-mediated protection is associated with restoration of the intestinal microbiota and metabolome, our understanding of its impact on host immune responses and restoration of colonic homeostasis remains incomplete. In this review, we focus on our current knowledge regarding the effects of FMT on host responses, including immune responses, colonic barrier restoration, and host metabolism. FMT is associated with restoration of immune signaling, which is depleted following antibiotic therapy. Restoration is associated with a shift towards type 2 and regulatory immune responses that limit intestinal inflammation and promote repair. FMT also modifies non-immune cells, promoting enhanced barrier integrity and significantly modifying host metabolism within the gut. FMT studies utilize a variety of experimental protocols and FMT formulations, and more mechanistic studies are required to understand how this variation impacts microbiota and host-directed changes. Better understanding of the immune and metabolic changes associated with protection against rCDI will allow for the design of more targeted therapeutics.