Effects of Lactulose on Gut Microbiota and Metabolism in Diabetic Constipated Patients

Chinese Academy of Medical Sciences & Peking Union Medical College

Status

Enrolling

Conditions

Constipation - Functional

Diabetes Mellitus

Treatments

Drug: Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules

Drug: Lactulose oral solution

Study type

Interventional

Funder types

Other

Identifiers

NCT07065942

I-23PJ993

Details and patient eligibility

About

Constipation is the most common gastrointestinal manifestation in diabetic patients. Emerging evidence suggests that gut microbiota dysbiosis may contribute to the pathogenesis of diabetes, highlighting the need to investigate its role in diabetic constipation, though current research remains limited.

Current management of diabetic constipation primarily relies on bulk-forming and osmotic laxatives. Additionally, microbiome-modulating agents (e.g., probiotics, prebiotics, and synbiotics) may serve as adjunctive therapies by regulating gut microbiota and enhancing intestinal motility. Lactulose, a well-tolerated osmotic laxative with prebiotic effects, is widely recommended in clinical guidelines. It promotes short-chain fatty acid production, increases fecal volume, and accelerates colonic transit, thereby alleviating constipation. However, its specific impact on gut microbiota composition and metabolic pathways in diabetic constipation remains unclear.

This study aims to explore changes in fecal microbiota and metabolomic profiles in diabetic patients with chronic constipation following treatment with lactulose alone or in combination with Bacillus subtilis-Enterococcus faecium probiotics, providing mechanistic insights into prebiotic therapy for this condition.

Enrollment

60 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age: 18-70 years
Type 2 Diabetes Diagnosis (per 2017 ADA criteria), meeting ≥1 of:
1. Fasting plasma glucose (FPG) ≥7.0 mmol/L
2. hour plasma glucose ≥11.1 mmol/L during 75g anhydrous oral glucose tolerance test (OGTT)
3. Random plasma glucose ≥11.1 mmol/L with hyperglycemia symptoms or hyperglycemic crisis
Functional Constipation (Rome IV criteria), requiring:
1. ≥2 of the following
  1. occurring in ≥25% of defecations
  2. Straining
  3. Lumpy/hard stools (Bristol Stool Scale 1-2)
  4. Sensation of incomplete evacuation
  5. Anorectal obstruction/blockage
  6. Manual maneuvers required
  7. <3 spontaneous bowel movements/week
2. No loose stools without laxatives
3. Exclusion of IBS diagnosis. Symptom duration >6 months, with active symptoms meeting criteria for last 3 months.
Stable Glycemic Control: No anticipated antidiabetic medication adjustments during study
Dietary Stability: Maintain consistent diet; avoid yogurt, fermented foods, prebiotic-containing processed foods, or other items that may confound results

Exclusion criteria

Secondary Constipation due to organic diseases or medication effects.
Constipation-predominant Irritable Bowel Syndrome (IBS-C).
Concurrent gastrointestinal disorders (e.g., inflammatory bowel disease, colorectal cancer).
Type 1 Diabetes Mellitus.
Severe chronic comorbidities, including:
1. Cardiopulmonary insufficiency
2. Cerebrovascular diseases
3. Psychiatric disorders
Recent use (within 1 month) of confounding medications:
1. Probiotics/prebiotics
2. Antibiotics
3. Laxatives (e.g., osmotic/stimulant agents)
4. Prokinetics