Abstract
Simple SummaryThe transfer of a normal intestinal microbial community from healthy donors by way of their fecal material into patients with various diseases is an emerging therapeutic approach, particularly to treat patients with recurrent or refractory C. difficile infections (CDI). This approach, called fecal microbiota transplant (FMT), is increasingly being applied to patients with hematologic and oncologic diseases to treat recurrent CDI, modulate treatment-related complications, and improve cancer treatment outcome. In this review paper, we discussed the principles and methods of FMT. We examined the results obtained thus far from its use in hematologic and oncologic patients. We also propose novel uses for the therapeutic approach and appraised the challenges associated with its use, especially in this group of patients.Understanding of the importance of the normal intestinal microbial community in regulating microbial homeostasis, host metabolism, adaptive immune responses, and gut barrier functions has opened up the possibility of manipulating the microbial composition to modulate the activity of various intestinal and systemic diseases using fecal microbiota transplant (FMT). It is therefore not surprising that use of FMT, especially for treating relapsed/refractory Clostridioides difficile infections (CDI), has increased over the last decade. Due to the complexity associated with and treatment for these diseases, patients with hematologic and oncologic diseases are particularly susceptible to complications related to altered intestinal microbial composition. Therefore, they are an ideal population for exploring FMT as a therapeutic approach. However, there are inherent factors presenting as obstacles for the use of FMT in these patients. In this review paper, we discussed the principles and biologic effects of FMT, examined the factors rendering patients with hematologic and oncologic conditions to increased risks for relapsed/refractory CDI, explored ongoing FMT studies, and proposed novel uses for FMT in these groups of patients. Finally, we also addressed the challenges of applying FMT to these groups of patients and proposed ways to overcome these challenges.
Highlights
The human intestinal tract is colonized by thousands of different microbial species
fecal microbiota transplant (FMT) has been tried in other conditions, such as in human irritable bowel syndrome [34,35] and autism spectrum disorder [36], and in mice and humans for multiple sclerosis [37,38] and in mice for Parkinson’s disease [39]. In all of these disease states, the target for FMT is the gut–brain axis, which may be related to the breakdown of the gut barrier functions due to changes in intestinal metabolomics, such as the decrease in the production of short chain fatty acids caused by alterations in the normal intestinal microbial composition
A meta-analysis of 23 observational studies involving more than 300,000 patients found that pump inhibitors (PPIs) use was associated with a 65% increase in the incidence of Clostridioides difficile infections (CDI) [50]
Summary
The human intestinal tract is colonized by thousands of different microbial species. In the last two decades, various studies have established the importance of these microbial organisms in maintaining and facilitating human health and well-being. Unlike in patients with CDI who usually have very restricted intestinal microbial diversity, bowel preparation with antibiotics may be even more important for successful FMT for non-CDI purposes Based on these considerations, the European Consensus Conference on FMT recommends that patients with recurrent CDI should receive three days of either vancomycin or fidaxomicin before the FMT procedure [10], we typically administer oral vancomycin for seven days prior to FMT in patients with active colitis, with the last dose being given 24 h before the procedure. Routine administration of oral antibiotics in the absence of active colitis is generally not recommended due to concerns of diminished efficacy, especially in patients with diarrhea-predominant irritable bowel disease, in which antibiotic pretreatment has been shown to signific3anoftl1y6 reduce bacterial engraftment [11]. A larger meta-analysis involving 24 studies reported that FMT by lower gastrointestinal endoscopy was superior to all other delivery methods [16]
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