Recipient factors in faecal microbiota transplantation: one stool does not fit all

Abstract

Fecal microbiota transplantation is a promising therapy for chronic diseases associated with gut microbiota alterations. FMT cures 90% of recurrent C. difficile infections. However, in complex diseases, such as inflammatory bowel disease, irritable bowel syndrome and metabolic syndrome, its efficacy remains variable. It is accepted that donor selection and sample administration are key determinants of FMT success, and great effort has been made to standardize these procedures.However, little is known about recipient factors impacting FMT success and long-term clinical improvement. In this review, we discuss the effects of the recipient parameters on donor microbiota engraftment and clinical efficacy. Especially, emerging evidence supports that controlling the inflammation level in the recipient's intestine might facilitate engraftment by reducing host immune system pressure on the newly transferred microbiota. Deciphering FMT engraftment rules and developing novel therapeutic strategies are priorities to alleviate the burden of chronic diseases associated with an altered gut microbiota.

Drivers and Determinants of Strain Dynamics Following Faecal Microbiota Transplantation

“…This donor-centric view has since been questioned at least for some indications 19 , highlighting the importance of recipient 20 or procedural 21 factors instead.…”

Intraspecies strain exclusion, antibiotic pretreatment, and donor selection control microbiota engraftment after fecal transplantation

“…3C), not only attesting to the efficacy of a now commonly used therapeutic option but also allowing for the causal inference of the gut microbiota in a human pathology (Walter et al 2020). More modest and inconsistent clinical benefits have been reported for the treatment of IBD (Danne, Rolhion, and Sokol 2021), ICI-refractory melanoma (Woelk and Snyder 2021), and MetS (Hanssen, de Vos, and Nieuwdorp 2021) with FMT. However, donor microbiota engraftment in these patient populations had previously also not been comprehensively characterized, compared and correlated to individual patient parameters, FMT modalities or clinical outcome parameters.…”

“…FMT has been validated in randomized controlled trials (RCTs) as a treatment for recurrent Clostridioides difficile infection (rCDI) with a success rate of~90%, surpassing that of conventional antibiotic treatment (Kao et al 2017; van Nood et al 2013). FMT efficacies in inducing remission in IBD patients with ulcerative colitis have generally been lower (24-32% versus 5-9% for placebo), but surpassed those reported in phase III clinical trials for several biological agents (golimumab and vedolizumab) (Danne, Rolhion, and Sokol 2021). Two recent trials suggest a potential role for FMT in cancer therapy, demonstrating re-induction of a response to anti-PD-1 immunotherapy in~30% of immune checkpoint inhibitor (ICI)-refractory melanoma patients (n=25) after FMT from patients that had previously responded to ICI (Davar et al 2021;Baruch et al 2021).…”

“…The population dynamics of post-FMT microbiota organization in patients from different medical backgrounds have not been extensively studied, and the clinical, host, and ecological factors that govern microbiome assembly at the level of individual patients and individual microbes are insufficiently understood (Danne, Rolhion, and Sokol 2021).…”

Recent Progress in Metabolic Syndrome Research and Therapeutics

“…Achieving precision medicine also necessitated the consideration and manipulation of baseline clinical characteristics of the recipients. For example, alleviating the initial inflammatory condition improved the engraftment of FMT [98]. Moreover, Alang et al noticed weight gain in some patients after FMT, and argued that the body composition of the donor matters as well [99].…”