The Impact of Probiotic Intervention on the Gut Microbiota and Bowel Function

The Impact of Probiotic Intervention on the Gut Microbiota and Bowel Function of Patients With Prophylactic Ileostomy for Ultra Low Rectal Cancer -a Multicenter Randomized Controlled Trial

This study aims to propose a novel, easy-to-operate intervention strategy that effectively improves defecation function after stoma reversal and to assess its impact on the gut microbiota.The efficacy and safety of antegrade placement of probiotics into the distal deserted intestine during prophylactic stoma to improve bowel function after stoma reversal were evaluated through randomized controlled clinical trials.Observing the changes in gut microbiota during the prophylactic stoma period, the impact of probiotics on the structure of gut microbiota, and exploring the correlation between gut genera and bowel function after stoma reversal.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Biological: Clostridium butyricum (live) Tablets(Meiya)

Detailed Description

This study includes patients with ultra low rectal cancer who underwent ISR（Intersphincteric Resection） and prophylactic ileostomy. Patients are randomly assigned to the low dose group,high dose group and the control group in a 1:1:1 ratio. The low dose group received interventions (4 Meiya pills, administered into the dysfunctional intestine once a week) starting 1 week after the ileostomy, the high dose group received interventions (4 Meiya pills, administered into the dysfunctional intestine twice a week) starting 1 week after the ileostomy, while the control group received routine postoperative follow-up. Evaluation indicators included bowel function and quality of life before the prophylactic ileostomy and 1 week, 2 weeks, 1 month, 3 months, and 6 months and so on until two years after the stoma reversal.

Fecal samples are collected prior to prophylactic ileostomy. Post-stoma reversal surgery, fecal samples are obtained from patients at their first defecation . All fecal samples underwent 16s rRNA gene sequencing and bioinformatic analysis to compare the microbial composition differences among three groups. Key genera associated with bowel function were identified through correlation analysis.

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Li Zhenyang, Doctor; Phone Number: +86-13764030915; Email: 13764030915@163.com
• Study Contact Backup: Name: Xiang Jianbin, Doctor; Phone Number: +86-13476272860; Email: xjbzhw@163.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200040
      • Recruiting
      • Huashan Hospital Fudan University
      • Contact: Li Zhenyang, Doctor; Phone Number: +86-13764030915; Email: 13764030915@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age between 18 and 75 years
2. Ultra low rectal cancer meeting the indication for Intersphincteric Resection (ISR) surgery
3. Underwent a prophylactic ileostomy
4. Scheduled for stoma reversal surgery within 6 months after the ISR procedure
5. Digestive tract reconstruction achieved via either hand-sewn or stapled coloanal anastomosis
6. Patient has a strong preference for undergoing sphincter-preserving surgery
7. Capable of understanding and willing to provide signed informed consent

Exclusion Criteria:

1. Does not meet the surgical indications for Intersphincteric Resection (ISR)
2. Presence of multiple primary colorectal malignancies
3. Patients who have received neoadjuvant radiotherapy
4. Patients who experience disease progression or death in the postoperative period
5. Patients who develop severe anastomotic complications postoperatively, such as anastomotic leakage or stenosis
6. Patients whose actual stoma reversal surgery occurs more than 6 months after the ISR procedure
7. Patients who require long-term(more than 3 months) use of antibiotics
8. History of allergy to Clostridium butyricum (live) Tablets (MIYA) or any of its components
9. Concurrent use of other probiotic during the study period
10. Coexisting inflammatory bowel disease
11. History of neurological or psychiatric disorders, including but not limited to Parkinson's disease, Alzheimer's disease, organic brain diseases, stroke, epilepsy, or major psychiatric disorders (e.g., major depressive disorder)
12. Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: high dose group; the high dose group received interventions (4 Clostridium butyricum (live) Tablets(Meiya), administered into the dysfunctional intestine twice a week) starting 1 week after the ileostomy	Biological: Clostridium butyricum (live) Tablets(Meiya); Clostridium butyricum (live) Tablet administered into the dysfunctional intestine for low dose and high dose group, while control group has no intervention
Experimental: low dose group; the low dose group received interventions (4 Clostridium butyricum (live) Tablets(Meiya), administered into the dysfunctional intestine once a week) starting 1 week after the ileostomy	Biological: Clostridium butyricum (live) Tablets(Meiya); Clostridium butyricum (live) Tablet administered into the dysfunctional intestine for low dose and high dose group, while control group has no intervention
No Intervention: control group; the control group received routine postoperative follow-up

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low Anterior Resection Syndrome Score（LARS Score）	Comparison of LARS scores among the three groups at one month postoperatively. Low Anterior Resection Syndrome (LARS) is characterized by major symptoms including difficulty defecating, urgency, incontinence of liquid stool, incontinence of flatus, and increased frequency of bowel movements. Based on severity, LARS can be classified as none (0-20 points), minor (21-29 points), or major (30-42 points) using LARS score. And higher scores mean a worse outcome.	One month after stoma reversal
microbial diversity	Fecal samples from study participants with ISR preoperatively and postoperatively will be collected to analyze the alpha and beta diversity of gut microbiota among the three groups	The first stool sample will be collected within one week before ISR surgery, and the second stool sample will be collected within three to five days after stoma reversal, upon the first bowel movement.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wexner Incontinence Score	The Wexner Incontinence Score (WIS) assesses the severity of incontinence from five aspects: solid stool incontinence, liquid stool incontinence, flatus incontinence, pad usage, and lifestyle alterations. The score ranges from 0 to 20, where 0 represents normal and 20 represents complete incontinence.	one month after ISR
Kirwan Incontinence Score	This grading system classifies anal incontinence into five grades (I-V) based on symptom severity: Grade I: No incontinence; Grade II: Incontinence to flatus or liquid stool; Grade III: Occasional solid stool incontinence; Grade IV: Frequent solid stool incontinence; Grade V: Requires a stoma (fecal diversion). Among these, Grades I-II indicate good continence function, while Grades III-IV indicate poor continence function.	one month after ISR
Exploratory LARS Scoring Instrument	An exploratory scoring instrument was used to determine the severity of 16 specific variables that were identified by the Delphi consensus for defining LARS. In accordance with the response range defined by the WIS, there were 5 frequency options ranging from never (meaning no episodes; score 0) to always (meaning 1 or more episodes/day; score 4) for each item. Given that social and psychological features (marital separation, divorce, widowed seniors, etc) may have an influence on "relationships and intimacy," its response category for "never" was replaced with dichotomous options of "none" and "N/A." The summary score, also called the Delphi consensus severity score, was used as an index for patient-reported severity of LARS, ranging from 0 (best) to 64 (worst).	one month after ISR
Fecal Incontinence Quality of Life (FIQL) Scale	The Fecal Incontinence Quality-of-Life (FIQL) Scale was used to analyze CSQoL. The FIQL entails 29 items that cover 4 domains: lifestyle (10 items), coping/behavior (9 items), depression/self-perception (7 items), and embarrassment (3 items).19 Each item has a range of 1 to 4 (except 2 items in depression/self-perception with ranges of 1-5 and 1-6). The score for each domain is the average of all items within its domain, and the global score is the mean of all domains. Higher scores indicate better CSQoL.	one month after ISR

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: First Affiliated Hospital of Fujian Medical University; Ruijin Hospital; Zhongnan Hospital; Nanfang Hospital, Southern Medical Universit; Characteristic Medical Center of Rocket Army; The First Affiliated Hospital of Nankai University
• Investigators: Principal Investigator: Xiang Jianbin, Doctor, Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2025
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: December 23, 2025
• First Submitted That Met QC Criteria: January 18, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 18, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: rectal cancer; bowel function; intersphincteric resection; probiotic intervention; prophylactic ileostomy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: KY2025-1273

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data that underlie the results reported in this article (text, tables, figures, and appendices) will be shared. The study protocol, statistical analysis plan, and informed consent form will also be available. Data will be available beginning 9 months and ending 36 months after article publication. Proposals for data access should be directed to the corresponding author. To gain access, data requestors will need to sign a data access agreement. Data will be provided via a secure online platform.
• IPD Sharing Time Frame: Data will be available beginning 9 months and ending 36 months after article publication.
• IPD Sharing Access Criteria: De-identified individual participant data will be available to qualified researchers whose proposals have been approved by an independent data access committee. Requestors must submit a scientifically sound research proposal and sign a data use agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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