A Clinical Study on The Use of DL-endopeptidase-producing Probiotics as an Adjunctive Therapy for Inflammatory Bowel Disease.

Shenzhen Hospital of Southern Medical University

Through a series of studies,the investigators has discovered for the first time that gut microbiota-derived DL-endopeptidase is a core regulator of the NOD2 pathway. This research also reveals a novel etiological mechanism in which deficiency of gut bacterial DL-endopeptidase leads to dysfunctional NOD2 signaling, thereby promoting the pathogenesis of inflammatory bowel disease (IBD).( The findings have been published in Cell Host & Microbe and Nature Communications.) Based on this, the investigators has successfully screened a high DL-endopeptidase-producing active strain, Lactobacillus rhamnosus CALM 607 (abbreviated as LR607), from the traditional probiotic Lactobacillus rhamnosus.(Its unique advantages include: 1) Independent intellectual property rights (patent applied for);2) DL-endopeptidase production and NOD2 regulatory ability 2.7 times higher than that of the conventional strain LGG;3) Preclinical experiments have demonstrated its potential to alleviate intestinal inflammation.) The investigators' Phase I clinical trial (data pending publication) has confirmed that LR607 has good safety and tolerability in healthy volunteers, providing a safety foundation for subsequent clinical studies.

Therefore, the investigators aim to investigate the DL-endopeptidase-producing probiotic LR607 through randomized controlled clinical intervention studies, to evaluate its adverse effects in adjunctive therapy and comprehensively assess its impact on the gut microbiome-NOD2 pathway, intestinal inflammation, and the progression of IBD.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammatory Bowel Disease (IBD)
• Intervention / Treatment: Dietary supplement: Lactobacillus rhamnosus CALM 607（LR607）

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Shenzhen Hospital of Southern Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with ulcerative colitis (UC) Patients diagnosed with UC according to the 'Chinese Guidelines for the Diagnosis and Treatment of Ulcerative Colitis (2023, Xi'an)'.

1. Patients with non-infectious UC initially diagnosed through laboratory tests, endoscopy, and pathological biopsy;
2. According to the latest guideline standards, clinically diagnosed with mild to moderate disease; defined as a modified Mayo score of 3-9 points; and classified as mild to moderate based on the modified Truelove and Witts severity classification;
3. In the active phase, with a clinical treatment plan using only mesalazine;
4. Voluntarily participating in this clinical trial, understanding, and signing the informed consent form.

2. Patients with Crohn's disease (CD) Patients diagnosed with Crohn's disease (CD) according to the 'Chinese Guidelines for the Diagnosis and Treatment of Crohn's Disease (2023, Guangzhou)'.

1. Patients with non-infectious Crohn's disease (CD) initially diagnosed through laboratory tests, endoscopic examination, and pathological biopsy;
2. Clinically diagnosed as having mild to moderate disease according to the latest guideline standards, defined as a Crohn's Disease Activity Index (BestCDAI) score of 150-450;
3. Voluntarily participating in this clinical trial, having understood and signed the informed consent form.

Exclusion Criteria:

1. Patients with ulcerative colitis (UC) Patients diagnosed with UC according to the 'Chinese Guidelines for the Diagnosis and Treatment of Ulcerative Colitis (2023, Xi'an)'.

1. Patients who have changed medication dosage or type in the past 2 months;
2. Patients who have the history of antibiotics, probiotics, or other medications affecting gut microbiota for non-target diseases within the past 2 months;
3. Patients who have the history of immunosuppressive drugs such as methotrexate or glucocorticoids ;
4. Patients who have the history of malignant tumors, other immune system diseases, or other serious chronic diseases;
5. Patients who have Concurrent active infections, including but not limited to obvious gastrointestinal bleeding, local or systemic infectious symptoms due to severe gastrointestinal ulceration or bleeding;
6. Pregnant or preparing for pregnancy and breastfeeding women;
7. Other situations deemed necessary to exclude by the researcher, for example: Simultaneous participation in other clinical interventional studies that may interact with this study.

2. Patients with Crohn's disease (CD) Patients diagnosed with Crohn's disease (CD) according to the 'Chinese Guidelines for the Diagnosis and Treatment of Crohn's Disease (2023, Guangzhou)'.

1. Patients who have changed medication dosage or type in the past 2 months;
2. Patients who have the history of antibiotics, probiotics, or other medications affecting gut microbiota for non-target diseases within the past 2 months;
3. Patients who have the history of malignant tumors, other immune system diseases, or other serious chronic diseases;
4. Patients who have Concurrent active infections, including but not limited to obvious gastrointestinal bleeding, local or systemic infectious symptoms due to severe gastrointestinal ulceration or bleeding;
5. Pregnant or preparing for pregnancy and breastfeeding women;
6. Other situations deemed necessary to exclude by the researcher, for example: Simultaneous participation in other clinical interventional studies that may interact with this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Take 2 grams of probiotic powder(LR607) daily from day 1 to day 5, and 4 grams daily from day 6 to day 90.	Dietary supplement: Lactobacillus rhamnosus CALM 607（LR607）; Take 2 grams of probiotic powder(LR607) daily from day 1 to day 5, and 4 grams daily from day 6 to day 90.
No Intervention: Control; Take 2 grams of placebo daily from days 1 to 5, and 4 grams daily from days 6 to 90.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Mayo endoscopic score	Modified Mayo endoscopic score is divided into diarrhea, blood in stool, mucosal appearance, and physician assessment, each with a score of 0 to 3.; Clinical remission: score <2 with no individual subscore >1 ;; Mild activity: 3-5 points;; Moderate activity: 6-10 points;; Severe activity: 11-12 points	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Levels of NOD2 in the gut		3 months
The changes in gut microbiota structure	The gut microbiota composition was assessed through metagenomics before and after one and three months of taking probiotics or placebo. Compare and analyze the differences in gut microbiota structure at the three time points.	3 months
Endoscopic scoring（SES⁃CD/UCEIS）	SES⁃CD（4 parts: Including ulcer size, the proportion of intestinal segments with ulcers, the proportion of intestinal segments with non-ulcerative lesions, and strictures, each with a score of 0 to 3. Score the five intestinal segments (rectum, descending colon, transverse colon, ascending colon, and ileum) separately and calculate the total.）： Remission phase: 0-2 points;; Mild activity: 3-6 points;; Moderate activity: 7-15 points;; Severe activity: ≥16 points; UCEIS（3 parts: Including vascular patterns(0-2 points), bleeding(0-3 points), and erosive ulcers(0-3points)）：; Remission phase: 0 points;; Mild activity: 1-3 points;; Moderate activity: 4-6 points;; Severe activity: 7-8 points;	3 months

Collaborators and Investigators

• Sponsor: Shenzhen Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: November 30, 2025
• First Submitted That Met QC Criteria: January 4, 2026
• First Posted (Estimated): January 6, 2026

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; IBD; Crohn's disease; gut microbiota; DL-endopeptidase
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Colitis; Colitis, Ulcerative; Crohn Disease; Inflammatory Bowel Diseases
• Other Study ID Numbers: ShenzhenHZHW

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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