Encapsulated Fecal Microbiota Transplantation: Development, Efficacy, and Clinical Application

Abstract

Fecal microbiota transplantation (FMT) has been established as a highly restorative therapeutic approach for treating recurrent Clostridioides difficile infection (rCDI). Recently, the use of capsule-based fecal microbiota transplantation (cFMT) has been shown to be a clinically effective approach to restore intestinal microbiota composition. This convenient, oral delivery provides an easy route of administration and a newfound flexibility for clinicians and patients. In this review, we discuss the development of cFMT, paying particular attention to lyophilized cFMT products. We review the available published clinical studies comparing cFMT with lower endoscopic FMT (eFMT) or placebo. We further discuss the pharmacokinetics of FMT, which should be understood in a framework of microbial ecology that considers the complex and dynamic interactions of gut microbiota with host factors and other microorganisms. Promisingly, the results of multiple trials investigating cFMT vs. eFMT in rCDI show cFMT to be as effective as eFMT at preventing rCDI. However, its efficacy in non-rCDI conditions, including obesity and metabolic syndrome, inflammatory bowel disease, HIV, and neurologic conditions, is less clear and more research is needed in these areas. Standardization of formulation, dose, and timing of administration to ensure optimal microbiota engraftment and clinical response is also a challenge to be addressed. Overall, cFMT is a practical method for fecal microbiota transplantation, with similar efficacy to eFMT in the resolution of rCDI, that holds therapeutic potential in a variety of other diseases.

Gut microbiome health and dysbiosis: A clinical primer

“…Fecal microbiota transplantation (FMT) has been shown to restore bacterial diversity in patients with recurrent CDI 46 and is currently recommended by clinical practice guidelines for this indication 44,47,48 . Investigational FMT has also been used for a variety of dysbiosis‐associated conditions outside of CDI, including graft‐versus‐host disease, malignancies, and decolonization of multidrug‐resistant organisms 36 . Notably, FMT is not standardized in its administration techniques nor is it FDA‐approved for any therapeutic indication.…”

“…43 Probiotics, defined as "live microorganisms which when administered in adequate amounts confer a health benefit to the host," are intended to have positive modulatory effects on the gut microbiome, including via pleiotropic effects. Common TA B L E 2 Diseases or conditions proposed to have gut microbiome-associated pathophysiology 3,14,25,36,39 or Saccharomyces species. 43 Although probiotics may be beneficial in certain scenarios (e.g., mitigation of antibiotic-associated diarrhea), they are not regulated by the United States Food and Drug Administration (FDA) and can pose safety concerns including risk of bloodstream infection in select high-risk populations such as the immunocompromised.…”

Evolutionary Insights Into Microbiota Transplantation in Inflammatory Bowel Disease

“…The diversity of gut microbiota is critical for maintaining resilience, and therefore, the transplantation of microbiota combinations is a potentially effective alternative for IBD treatment. Previous articles on microbiota transplantation were mainly limited to FMT, and most of them focused on the application of FMT in IBD, or emphasized the importance of the gut microbes in the pathogenesis and treatment of IBD ( Zuo and Ng, 2018 ; Ooijevaar et al., 2019 ; Tan et al., 2020 ; Lee and Chang, 2021 ; Underhill and Braun, 2022 ; Halaweish et al., 2022 ). We mainly analyzed different microbiome-based interventions currently applied in IBD clinical trials, including FMT, WMT (a method that removes adverse factors in natural FMT by special washing manner), as well as ACT, which combines different and limited microorganisms, and analyzed the possible combination principles of ACT.…”

“…In addition to direct colon FMT, oral capsule FMT (cFMT) is well tolerated in mild to moderate UC patients (Crothers et al, 2021). Also, there are currently several registered trials investigating the efficacy of cFMT in IBD, as the previous Halaweish et al described (Halaweish et al, 2022). Oral cFMT is a more acceptable alternative for UC treatment than the direct colon FMT, and it may enhance the potential of long-term microbial-based treatment strategies.…”

Research trends on clinical fecal microbiota transplantation: A biliometric analysis from 2001 to 2021

“…Although a decline in microbial viability has been reported in frozen stool compared to fresh stool, their efficacy was comparable in clinical resolution of patients with rCDI ( 30 ). With the development of encapsulation technique, the application of oral capsule will on the rise in the future as it not only achieved similar efficacy to colonoscopy delivery in treating rCDI but also noninvasive, convenient and esthetic to patients ( 31 ). No matter the fecal material used in FMT is fresh or frozen, it is vital to choose the optimal donors that largely determines the success rate of FMT.…”