Autologous Fecal Microbiota Transplantation for Diversion Colitis

Autologous Fecal Microbiota Transplantation Via the Diverting Stoma Ameliorates Diversion Colitis in Patients With Temporary Ileostomy for Rectal Cancer: A Randomized Controlled Trial With Endoscopic and Histopathological Assessment

Diversion colitis (DC) is a common inflammatory complication in patients with temporary ileostomy after rectal cancer surgery, and no standardized medical treatment exists. This prospective, assessor-blinded, parallel-group, randomized controlled trial evaluated whether autologous fecal microbiota transplantation (auto-FMT) delivered through the diverting stoma ameliorates DC and improves post-reversal outcomes. Sixty-six patients with endoscopically confirmed DC were randomized 1:1 to receive daily auto-FMT (n=33) or saline irrigation (n=33) for four weeks. The primary endpoints are changes from baseline to week 4 in endoscopic (modified Harig score, 0-12) and histopathological (0-9) scores. Secondary endpoints include Wexner incontinence score, quality of life (EORTC QLQ-C30/CR29), inflammatory biomarkers, and safety. The study is designed to test whether auto-FMT produces superior improvements in endoscopic and histopathological severity compared with saline control, and leads to better functional outcomes after stoma reversal.

Study Overview

• Status: Completed
• Conditions: Diversion Colitis
• Intervention / Treatment: Other: Autologous Fecal Microbiota Transplantation (auto-FMT); Other: saline irrigation

Detailed Description

Background and Rationale

Diversion colitis frequently develops after fecal stream diversion, affecting most patients whose intestinal continuity remains interrupted for more than three to six months. While stoma reversal is definitive, many patients require prolonged diversion due to adjuvant chemotherapy, poor general condition, or anastomotic healing concerns. Existing medical therapies-including short-chain fatty acid enemas, 5-aminosalicylates, corticosteroids, and probiotics-lack consistent efficacy in randomized trials. Gut microbiota dysbiosis is a central driver of DC; restoring a diverse microbial community via fecal microbiota transplantation represents a rational approach. Autologous FMT using the patient's own stoma effluent avoids pathogen transmission, donor screening, and ethical concerns. However, no prospective RCT has systematically evaluated auto-FMT for DC using endoscopic and histopathological endpoints.

Study Design

Single-center, prospective, assessor-blinded, parallel-group, superiority randomized controlled trial with a 1:1 allocation ratio.

Participants

Adults aged 18-75 years with histopathologically confirmed rectal adenocarcinoma who underwent low anterior resection with temporary loop ileostomy, scheduled for reversal at 3-6 months after primary surgery, and with endoscopic DC (modified Harig score ≥4 at week 4 post-ileostomy). Key exclusion criteria: neoadjuvant chemoradiotherapy, pre-existing inflammatory bowel disease, recent antibiotic or probiotic use, severe organ dysfunction, pregnancy, or lactation.

Interventions

Auto-FMT group: Daily irrigations of autologous fecal microbiota suspension for 4 weeks. Preparation: 50-80 g of fresh stool collected from the patient's stoma bag within 2 hours of passage, homogenized with 500 mL sterile normal saline (0.9% NaCl) pre-warmed to 37°C, stirred, and filtered through two layers of sterile gauze. The filtrate was used within 30 minutes. Irrigation: a 14-16 French Foley catheter inserted 10-15 cm into the efferent limb of the loop ileostomy; suspension infused by gravity drip over 5-10 minutes; patients retained the suspension for at least 30 minutes before evacuation.

Control group: Daily irrigations of 500 mL sterile normal saline (37°C) using the same catheter and technique, with the same retention time.

Outcome Measures

Primary outcomes: Change from baseline to week 4 in endoscopic score (modified Harig score, 0-12) and histopathological score (composite of mucosal atrophy, crypt distortion, and inflammatory infiltrate, 0-9), assessed by blinded reviewers.

Secondary outcomes: Wexner incontinence score at 1, 3, and 6 months after stoma reversal; quality of life (EORTC QLQ-C30 and QLQ-CR29) at baseline, week 4, and 6 months post-reversal; serum hs-CRP, albumin, and fecal calprotectin at baseline and week 4; adverse events (CTCAE v5.0); treatment adherence (≥80% of 28 sessions).

Sample Size

33 patients per group (total 66) to detect a mean endoscopic score reduction difference of 1.5 points (assuming SD 2.0 in auto-FMT group and SD 1.8 in control group), 80% power, two-sided α = 0.05, accounting for a 20% dropout rate.

Statistical Analysis

Primary analysis was intention-to-treat. Change scores were analyzed using ANCOVA with baseline score as covariate. Secondary outcomes: Wexner scores with generalized estimating equations; quality of life with ANCOVA; biomarkers with Mann-Whitney U tests. Missing data were handled with multiple imputation. Two-tailed p < 0.05 was considered significant.

Ethical Approval

The protocol was approved by the Ethics Committee of Lin'an First People's Hospital, Hangzhou (Approval No.: Lin'an First People's Hospital Lun Yan Shen 2022 No.20, dated April 29, 2022). Written informed consent was obtained from all participants. The study followed the Declaration of Helsinki.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 311300
      • Department of Colorectal Surgery, The First People's Hospital of Lin'an District, Hangzhou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histopathologically confirmed rectal adenocarcinoma.
• Low anterior resection with temporary loop ileostomy.
• Age 18-75 years.
• Scheduled for ileostomy reversal at 3-6 months after primary surgery.
• Endoscopic confirmation of diversion colitis at week 4 post-ileostomy (modified Harig score ≥4, range 0-12).
• Written informed consent.

Exclusion Criteria:

• Neoadjuvant chemoradiotherapy.
• Pre-existing inflammatory bowel disease, irritable bowel syndrome, or chronic constipation.
• Previous colorectal surgery (other than index surgery).
• Active infection requiring systemic antibiotics within 4 weeks before enrollment.
• Use of probiotics, prebiotics, or antibiotics within 4 weeks before enrollment.
• Severe organ dysfunction (Child-Pugh B/C cirrhosis, end-stage renal disease).
• Pregnancy or lactation.
• Any condition precluding protocol compliance or outcome assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous Fecal Microbiota Transplantation (auto-FMT); Daily irrigations of autologous fecal microbiota suspension via the diverting stoma for 4 weeks. Preparation: 50-80 g of fresh stool collected from the patient's stoma bag within 2 hours of passage, homogenized with 500 mL of sterile normal saline (0.9% NaCl) pre-warmed to 37 °C, stirred, and filtered through two layers of sterile gauze. The filtrate is used within 30 minutes. Irrigation: A 14-16 French Foley catheter inserted 10-15 cm into the efferent limb of the loop ileostomy, balloon inflated with 5-8 mL of air. The suspension is infused by gravity drip (bag 40-50 cm above stoma) over 5-10 minutes. Patients retain the suspension for at least 30 minutes before evacuation. Vital signs are monitored for the first 3 days.	Other: Autologous Fecal Microbiota Transplantation (auto-FMT); Daily irrigation of autologous fecal microbiota suspension via the diverting stoma for 4 weeks.
Other: Saline Irrigation; Daily irrigations of 500 mL sterile normal saline (0.9% NaCl) pre-warmed to 37 °C via the diverting stoma for 4 weeks. A 14-16 French Foley catheter is inserted 10-15 cm into the efferent limb of the loop ileostomy, and the balloon is inflated with 5-8 mL of air. Saline is infused by gravity drip (bag 40-50 cm above stoma) over 5-10 minutes. Patients retain the saline for at least 30 minutes before evacuation.	Other: saline irrigation; Daily irrigation of 500 mL sterile normal saline (0.9%) at 37°C via the diverting stoma, using the same catheter and technique as the auto-FMT group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Endoscopic Score	Change from baseline to week 4 in modified Harig score (0-12), evaluating edema/erythema, loss of vascular pattern, friability/contact bleeding, and erosions/ulcerations (each 0-3). Higher scores indicate more severe inflammation. A blinded colorectal endoscopist performed colonoscopy through the stoma at week 0 and week 4.	Baseline and Week 4
Change in Histopathological Score	Change from baseline to week 4 in composite histopathological score (0-9), assessing mucosal atrophy, crypt distortion, and inflammatory infiltrate (each 0-3). The average score of two blinded gastrointestinal pathologists was used; disagreements (>2 points) were resolved by joint review.	Baseline and Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wexner Incontinence Score	Wexner incontinence score (0-20, where 0 = perfect continence, 20 = complete incontinence) assessed at 1, 3, and 6 months after stoma reversal.	Month 1, Month 3, Month 6 post-reversal
Quality of Life - EORTC QLQ-C30 Global Health Status	Global health status / quality of life score from the EORTC QLQ-C30 questionnaire. Higher scores indicate better quality of life.	Baseline, Week 4, and Month 6 post-reversal
Quality of Life - EORTC QLQ-CR29	Disease-specific quality of life assessed by the EORTC QLQ-CR29 module, covering symptoms and functioning domains relevant to colorectal cancer patients.	Baseline, Week 4, and Month 6 post-reversal
Serum hs-CRP Level	High-sensitivity C-reactive protein (hs-CRP) measured in mg/L from serum samples.	Baseline and Week 4
Serum Albumin Level	Albumin concentration measured in g/L from serum samples.	Baseline and Week 4
Fecal Calprotectin Level	Fecal calprotectin concentration measured by ELISA (μg/g), as a biomarker of intestinal inflammation.	Baseline and Week 4
Adverse Events and Treatment Adherence	Adverse events graded according to CTCAE v5.0 (incidence, severity, and causality). Treatment adherence defined as completion of ≥80% of 28 scheduled irrigation sessions.	Throughout the 4-week intervention period for adverse events; at end of intervention for adherence

Collaborators and Investigators

• Sponsor: Yongjian Liao

Publications and helpful links

General Publications

• Wang JW, Kuo CH, Kuo FC, Wang YK, Hsu WH, Yu FJ, Hu HM, Hsu PI, Wang JY, Wu DC. Fecal microbiota transplantation: Review and update. J Formos Med Assoc. 2019 Mar;118 Suppl 1:S23-S31. doi: 10.1016/j.jfma.2018.08.011. Epub 2018 Sep 1.
• Sam SW, Hafeez B, Ong HI, Gill S, Smibert O, Lavelle A, Burgess A, Proud D, Mohan H. The impact of faecal diversion on the gut microbiome: a systematic review. Gut Microbiome (Camb). 2024 Feb 19;5:e4. doi: 10.1017/gmb.2024.1. eCollection 2024.
• Sohara N, Hagiwara S, Arai R, Iizuka H, Onozato Y, Kakizaki S. Can endoscopic submucosal dissection be safely performed in a smaller specialized clinic? World J Gastroenterol. 2013 Jan 28;19(4):528-35. doi: 10.3748/wjg.v19.i4.528.
• Vajn K, Suler D, Plunkett JA, Oudega M. Temporal profile of endogenous anatomical repair and functional recovery following spinal cord injury in adult zebrafish. PLoS One. 2014 Aug 26;9(8):e105857. doi: 10.1371/journal.pone.0105857. eCollection 2014.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): March 31, 2025
• Study Completion (Actual): September 30, 2025

Study Registration Dates

• First Submitted: June 15, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Autologous Fecal Microbiota Transplantation; Diversion Colitis
• Other Study ID Numbers: 2022-YJ-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in this manuscript will be made available to researchers who provide a methodologically sound proposal, for the purpose of individual participant data meta-analysis or other approved research. The study protocol, statistical analysis plan, and informed consent form will also be available. Data will be accessible immediately after publication, upon reasonable request to the corresponding author.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No