The American Gastroenterological Association (AGA) has formulated this guideline to offer guidance on applying fecal microbiota-based therapies for adults experiencing recurrent healthcare-associated infections (HAI). Specifically, inflammatory bowel diseases, encompassing pouchitis, and irritable bowel syndrome, and a main focus on Clostridioides difficile infection (CDI). Fecal microbiota-based therapies serve as an effective treatment to prevent recurrent C difficile in certain patients and act as a supportive therapy for those with severe or fulminant CDI unresponsive to standard antibiotics. However, its use for other gastrointestinal conditions is not yet supported outside of clinical trials.
The guideline committee issued 7 recommendations highlighting the selective use of fecal microbiota-based therapies after completing standard antibiotics to avoid recurrence. In adults with mild or moderate immunocompromise experiencing recurrent CDI, the AGA advises the selective employment of conventional FMT while recommending against its use in severely immunocompromised patients due to safety concerns. In cases of adults hospitalized with severe or fulminant CDI resistant to antibiotics, conventional FMT is endorsed selectively.
“Clinically significant diarrhea is common in many conditions that compromise the immune system, making the diagnosis of CDI more challenging,” according to the investigators. “In addition, C difficile colonization rates are higher in many immunocompromised populations. Therefore, a lack of response to anti-CDI antibiotics could suggest symptomatic colonization, and alternative etiologies of diarrhea should be considered. Furthermore, the driver of dysbiosis in immunocompromised individuals may not be ameliorated after FMT.”
3 Key Takeaways
- Fecal microbiota-based therapies are recommended for preventing recurrent CDI in immunocompetent adults and selectively in those with mild to moderate immunocompromise, but not in severely immunocompromised patients due to safety concerns.
- Fecal microbiota-based therapies serve as an effective treatment to prevent recurrent C difficile in certain patients and act as a supportive therapy for those with severe or fulminant CDI unresponsive to standard antibiotics
- The AGA advises against FMT use for inflammatory bowel diseases and irritable bowel syndrome outside clinical trials, underscoring the need for more evidence.
The guideline was crafted utilizing the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework. To formulate recommendations regarding the use of fecal microbiota-based therapies in the outlined gastrointestinal conditions, the guideline panel applied the Evidence-to-Decision framework to ensure a thorough evidence synthesis and to provide practical recommendations for clinical settings.
“The FDA Clinical Review Memoranda for both FDA-approved products reported the data to be insufficient to assess for difference in safety and efficacy in immunocompromised individuals.70,71 In addition, the guideline panel has concerns over the stool donor process used for these FDA-approved products,” according to the investigators. “The World Health Organization (WHO) states, that an adequate and reliable supply of safe blood can be assured by a stable base of regular, voluntary, unpaid blood donors. These donors are also the safest group as the prevalence of bloodborne infections is lowest among this group.”
Due to very low certainty evidence, the use of FMT in immunocompromised adults carries conditional recommendations. The decision to proceed with FMT requires a shared decision-making process, considering specific patient risks and preferences. There is insufficient evidence to recommend specific fecal microbiota products for this population, and concerns have been raised regarding the potential for transmission of emerging infections through stool.
Overall, the guideline emphasizes the selective use of fecal microbiota-based therapies, particularly in the context of CDI, which represents an area of concern due to the potential for recurrence and complications in immunocompromised individuals. A need for further research, given the insufficient evidence to recommend specific fecal microbiota products and concerns about the potential transmission of infections through stool. By addressing these gaps and implementing strict safety standards in the donor process, there would be more effective management of CDI and other gastrointestinal healthcare challenges.
Reference
Peery A, Kelly C, Kao D, Imdad A, Altayar O, et. al. AGA Clinical Practice Guideline on Fecal Microbiota–Based Therapies for Select Gastrointestinal Diseases. Gastroenterology. Published March 2024. Accessed February 27, 2024. doi: https://doi.org/10.1053/j.gastro.2024.01.008
