P400 - Fecal Microbiota Transplantation (FMT) for Recurrent Uncomplicated Diverticulitis: Results of a Pilot Study

Abstract Podium Presenter(s)

• 

  Andrew Hu, MD

  General Surgery Resident
  UMass Chan Medical School
  University of Massachusetts T.H Chan Medical School
  Worcester, MA, United States

  All disclosed relationships have been reviewed and managed prior to the start of this activity. Any relevant relationships will be listed below. This individual has no financial relationships to disclose

Author(s)

• CB

  Catherine Beauharnais, MD, MPH, MS

  Fellow
  University of Minnesota
  University of Minnesota
  Minneapolis, MN, United States

  Disclosure information not submitted.
• 

  Benjamin Gallant, MD

  General Surgery Resident
  UMass Chan Medical School
  UMass Chan Medical School
  Worcester, MA, United States

  Disclosure information not submitted.
• AO

  Alexandra Onyiego, MD

  General Surgery Resident
  Tulane University School of Medicine
  New Orleans, Louisiana, United States

  Disclosure information not submitted.
• DW

  Doyle V. Ward, PhD

  Associate Professor
  UMass Chan Medical School
  Worcester, Massachusetts, United States

  Disclosure information not submitted.
• BM

  Beth McCormick, Ph.D, AGAF

  Professor and Chair
  UMass Chan Medical School
  Worcester, Massachusetts, United States

  Disclosure information not submitted.
• PS

  Paul R. Sturrock, MD

  Assistant Professor of Surgery
  UMassMemorial Medical Center
  Worcester, Massachusetts, United States

  Disclosure information not submitted.
• 

  Tess H. Aulet, MD (she/her/hers)

  Colorectal Surgeon
  UMass Memorial Medical Center
  UMass Memorial Medical Center
  Worcester, Massachusetts, United States

  All disclosed relationships have been reviewed and managed prior to the start of this activity. Any relevant relationships will be listed below. This individual has no relevant financial relationships.
• TP

  Thomas Peponis, MD, FACS

  Colon and Rectal Surgeon, Assistant Professor of Surgery
  University of Massachusetts
  Worcester, Massachusetts, United States

  All disclosed relationships have been reviewed and managed prior to the start of this activity. Any relevant relationships will be listed below. This individual has no financial relationships to disclose
• 

  Karim Alavi, MD, MPH

  Associate Professor of Surgery, Director, Colon and Rectal Surgery Fellowship
  UMass Chan Medical School
  southborough, Massachusetts, United States

  Disclosure information not submitted.

Senior Author(s)

• 

  Justin Maykel, MD

  Chief, Division of Colorectal Surgery
  UMass Memorial Health
  UMass Chan Medical School
  Worcester, MA, United States

  All disclosed relationships have been reviewed and managed prior to the start of this activity. Any relevant relationships will be listed below. Olympus Corporation: Consultant (Ongoing); Safeheal: Consultant (Ongoing)

Purpose/Background: Uncomplicated diverticular disease is increasingly prevalent in the adult U.S. population. Standard treatment of uncomplicated diverticulitis includes antibiotic therapy and surgical resection for recurrent disease. Fecal microbiota transplantation (FMT) has been employed as part of the treatment algorithm for Clostridium difficile colitis. This pilot study aims to assess the safety and efficacy of FMT in treating recurrent, uncomplicated diverticulitis as an alternative to surgery. We also aim to assess changes in the microbiota of patients following FMT.

Methods/Interventions: We performed a prospective pilot study evaluating the use of FMT in patients with recurrent, uncomplicated diverticulitis. Eligible subjects had multiple episodes of uncomplicated colonic diverticulitis and were considered candidates for surgical resection. Patients with active acute diverticular flares and complicated disease were excluded. Enrolled subjects underwent FMT via colonoscopy utilizing transplant donors from the University of Minnesota's Microbiota Therapeutics Program. Recipients were followed for 12 months with follow-up visits at 1, 3, 6, and 12 months post-FMT. Baseline donor and recipient stool samples were collected. Recipient stool samples were collected weekly for the first 4 weeks, then at every follow-up visit. Clinical endpoints captured at each follow-up visit included: number of diverticular flares, antibiotic courses, ER visits, or hospitalizations since FMT. Per sample species composition was determined using Metaphlan3. Sample dissimilarity was then calculated using the unweighted unifrac metric as implemented in the QIIME2 software package. Within-sample dissimilarities were normalized to the baseline-donor sample dissimilarity, which was set as 100. This trial is registered at ClinicalTrials.gov (NCT05373784).

Results/Outcomes: Ten patients were recruited, and eight completed the study to date. The cohort was Caucasian (n=10, 100%), 50% female, with a mean age of 57 years (SD 11.4). There was a significant decrease in the average number of lifetime CT-confirmed diverticulitis flares following FMT (3.9 vs. 0.2, p < 0.0001). When compared to average CT-confirmed diverticulitis flares one year before FMT, there was still a significant decrease (1 vs. 0.2, p-value = 0.005). To date, 2 subjects (20%) had a recurrent diverticular flare confirmed on CT scan requiring antibiotics: one at 3 months and one at 12 months. The most common adverse events across the study period were abdominal discomfort and diarrhea, reported in 80% of the sample. There have been no hospital admissions, serious adverse events, or emergent surgical procedures due to diverticulitis to date. One patient did elect to undergo elective sigmoid colectomy due to a second diverticulitis flare one month following completion of the study. Recipient microbiome samples all show a dramatic shift away from baseline at 1 week following FMT, which persists throughout their follow-up analyses.

Conclusion/Discussion: Our findings support FMT as a safe alternative approach for treating patients with recurrent, uncomplicated diverticulitis. Donor microbiomes successfully integrated into recipients and remained stable for over one year. Further multi-institutional, randomized studies are warranted to evaluate the efficacy of this novel, non-operative therapeutic strategy.

Figure 1: Relative Similarity between Subject Sample to Donor Sample Over Time