Fecal Microbiota Transplant for Hematologic and Oncologic Diseases: Principle and Practice

Abstract

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.

Keywords: challenges; fecal microbiota transplant; hematologic diseases; oncologic diseases; outcome.

Figure 1

The two steps of fecal microbiota transplant. In Step 1, patients undergo bowel preparation with oral antibiotics followed by laxative. At least 24 h after the last dose of oral antibiotics, the patient will receive the donor fecal material via capsule, naso-enteral tubes, or upper or lower gastrointestinal endoscopy.

Figure 2

Fecal microbiota transplant restores intestinal microbial composition to modulate the adaptive immune responses, re-establish intestinal microbial homeostasis, and alter the host metabolism. Short chain fatty acids such as butyrate and propionate interact with G-protein coupled receptors GPR-43/41 on L cells to produce glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), which contributes to reducing food intake and improving glucose metabolism [17].

Figure 3

Patients with hematologic and oncologic diseases are more likely to develop Clostridioides difficile infection due to the frequent use of antibiotics, opioid analgesia and proton pump inhibitors, chemoradiation, and immunosuppressive agents. As a result, a change in the intestinal microbial composition and integrity of the epithelium results in the reduced production of short chain fatty acids, intestinal dysbiosis, thinning of the mucin layers, immune dysregulation, interruption to tight-junction formation, increased translocation of luminal microbes into the systemic circulation, and the development of Clostridioides difficile infections.