Inflammatory Bowel Disease (IBD)
Conditions
Keywords
gut microbiota, IBD, Crohn's disease, Ulcerative Colitis, DL-endopeptidase
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTLactobacillus 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.
Sponsors
Shenzhen Hospital of Southern Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Mayo endoscopic score | 3 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The changes in gut microbiota structure | 3 months | 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. |
| The Levels of NOD2 in the gut | 3 months | — |
| Endoscopic scoring（SES⁃CD/UCEIS） | 3 months | 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; |
Countries
China
Outcome results
None listed