AGA Supports Fecal Microbiota-Based Therapies for C Diff in New Guideline

The American Gastroenterological Association (AGA) has released the first comprehensive evidence-based guideline on the use of fecal microbiota-based therapies for gastrointestinal disease, recommending fecal microbiota transplant (FMT) in most cases of recurrent Clostridioides difficile infection (CDI).¹

Specifically, the guideline recommends the use of FMT-based therapy in patients with recurrent CDI at high risk of recurrence following standard-of-care antibiotics and in hospitalized patients with severe CDI after standard-of-care antibiotics if there is no improvement. Of note, the AGA does not recommend FMT therapies for inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS).¹

“Using fecal microbiota transplant, we take stool from a healthy donor and transfer it to the colon of the person with recurrent C. diff, restoring balance to their gut microbiome,” Anne Peery, MD, associate professor of medicine and director of the adult inpatient nutrition support team at the University of North Carolina School of Medicine, said in a press release.¹ “FMT is a safe and effective treatment with enough scientific evidence to be offered to most patients with two or more C. diff recurrences.”

The guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis. The guideline panel comprised 3 members of the AGA guideline committee, a senior methodologist, a junior methodologist, and 3 experts in fecal microbiota-based therapies. Of note, a patient representative also participated in the development of recommendations.²

The guideline panel identified 7 clinically relevant questions to address the use of fecal microbiota-based therapies in adults for the management of recurrent CDI or conventional FMT for severe to fulminant CDI, IBD, and IBS. The clinical questions were formulated using the PICO format, and the panel selected desirable and undesirable patient-important outcomes and summarized the evidence for each of the questions.²

Randomized controlled trials were used to address PICO questions, but investigators supplemented with observational comparative studies and single-arm observational studies as needed when other evidence was not available. The intervention of interest was the administration of fecal microbiota-based therapies. Accordingly, investigators considered studies with conventional FMT using unrelated and minimally manipulated donor stool, FDA-approved fecal microbiota, live-jslm , FDA-approved fecal microbiota spores, live-brpk, and the investigational product CP101.²

Investigators conducted a literature search on electronic databases including Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, MEDLINE, and Embase, also searching for ongoing trials at www.clinicaltrials.gov. Each relevant title and abstract underwent screening, and studies that met the criteria for inclusion underwent full-text review for final inclusion for evidence synthesis. In total, 66 studies were included in the review to inform the clinical guidance.²

Using the Evidence-to-Decision framework, the guideline panel developed 7 recommendations for the use of fecal microbiota-based therapies in specific gastrointestinal conditions and provided implementation considerations for clinical practice. The guideline recommendations are intended to provide the basis for rational informed decision-making for patients and healthcare professionals using fecal microbiota-based therapies for adults with recurrent CDI or conventional FMT for severe to fulminant CDI, IBD, and IBS.²

In immunocompetent adults with recurrent CDI, the guideline suggests select use of fecal microbiota-based therapies after completion of standard-of-care antibiotics to prevent recurrence. Additionally, the AGA recommends select use of conventional FMT in mildly or moderately immunocompromised adults with recurrent CDI as well as in adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics.²

In severely immunocompromised adults, the AGA does not recommend the use of any fecal microbiota-based therapies to prevent recurrent CDI. The guideline also suggests against the use of conventional FMT as treatment for IBD or IBS, except in the context of clinical trials.²

“C. diff is debilitating. Thanks to this new American Gastroenterological Association guideline, patients will suffer for shorter periods of time and be able to get back to leading happy and healthy lives,” Amanda Kabage, MS, FMT, researcher and FMT recipient who contributed to the development of the guideline, said in a press release.¹

References:

1. ^{American Gastroenterological Association. AGA now recommends fecal microbiota transplant for the majority of recurrent C. diff patients. February 21, 2024. Accessed February 21, 2024.}
2. ^{Peery AF, Kelly CR, Kao D, et al. American Gastroenterological Association Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases. Gastroenterology. https://www.gastrojournal.org/article/S0016-5085(24)00041-6/fulltext}