Q&A: Successful FMT linked with changes in blood
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MicroRNAs showed that fecal microbiota transplants are effective for treating infections like Clostridioides difficile infection, according to a study published in Gastroenterology.
Tanya M. Monaghan, MD, clinical associate professor, honorary consultant in gastroenterology, and Anne McLaren Fellow in the School of Medicine at the University of Nottingham, and colleagues assessed sera from two prospective multicenter randomized controlled trials on FMT. The researchers observed changes in patient microRNAs in the blood following the FMT.
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They also reported that specific microRNAs could protect bowel cells from damage induced by toxins from bacteria.
Healio Gastroenterology spoke with Monaghan about the results of the study and why FMT is effective for treatment of infections.
Healio: What were the key take-aways from this study?
Monaghan: We discovered that C. difficile, through its toxins, suppresses expression of a specific set of microRNAs in the circulation of infected patients. These toxins highjack the molecular mechanism important for microRNA maturation, a process important for microRNA activity. We have gone on to show that successful FMT for recurrent C. difficile (rCDI) can reverse these effects. We have identified the upregulation of several specific microRNAs in the circulation of patients undergoing FMT for rCDI. We validated these microRNAs in animal models and human colonoids (miniguts) and further demonstrated that FMT-regulated microRNAs target interleukin-12 subunit beta, IL-18, and fibroblast growth factor 21 and TNF Receptor Superfamily Member 9. Finally, we show that a combination of specific microRNAs can protect the intestinal barrier (cytoprotection) against the effects of C. difficile bacterial toxins.
Healio: How does “poo” effectively treat C. difficile?
Monaghan: The precise mechanisms by which poo transplants help treat C. difficile are not fully understood. It is thought that an FMT works by repopulating the patient’s gut with diverse microorganisms that may block C. difficile spores from germinating and propagating disease via release of its harmful toxins, which cause inflammation of the bowel and debilitating diarrheal symptoms. Recent research suggests that rather than FMT requiring live, intact bacteria for its efficacy, other mechanisms including more soluble factors such as gut microbiota-derived metabolites may mediate its mechanism of action. It is also thought that FMT may also work by downregulating pro-inflammatory immune responses. Overall, there are likely to be many reasons underpinning the efficacy of this treatment.
Healio: Why did you look at whether microRNAs changed following a successful FMT?
Monaghan: MicroRNAs are master regulators of gene expression. A single microRNA can modulate multiple RNA and protein molecules, affecting a vast array of cell functions. Given their importance in many human disorders, we sought to investigate their role in FMT.
Healio: What is the next step in your research?
Monaghan: Since we have demonstrated that successful FMT is associated with microRNA changes, we will next investigate if we can use these microRNAs to monitor or predict a patient’s response to FMT. We also plan to test the effects of these cytoprotective microRNAs alone and in combination with standard antimicrobial therapies in animal models of C. difficile infection.
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