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

Обзор

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.

Вмешательства

• Препарат Lactulose oral solution
  Oral, 30 mL once daily administered during breakfast.
• Препарат Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules
  Oral, 2 tablets (500 mg per tablet) three times daily (TID).

Первичные конечные точки

• Changes in Constipation Symptom Scores Pre- and Post-Treatment [Срок оценки: From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment]
• Changes in Fecal Microbiota Composition (16S rRNA and Metagenomics) [Срок оценки: From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment]
• Temporal Changes in Fecal Untargeted Metabolomics Profiles [Срок оценки: From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment]

Вторичные конечные точки (2)

• Changes in Fasting Blood Glucose and Glycated Albumin Levels [Срок оценки: From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment]
• Changes in Blood Lipid Profiles (Total Cholesterol, Triglycerides, HDL-C, and LDL-C) [Срок оценки: From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment]

Критерии участия

Критерии включения

• Age: 18-70 years
• Type 2 Diabetes Diagnosis (per 2017 ADA criteria), meeting ≥1 of:

• Fasting plasma glucose (FPG) ≥7.0 mmol/L
• hour plasma glucose ≥11.1 mmol/L during 75g anhydrous oral glucose tolerance test (OGTT)
• Random plasma glucose ≥11.1 mmol/L with hyperglycemia symptoms or hyperglycemic crisis
• Functional Constipation (Rome IV criteria), requiring:

• ≥2 of the following

• occurring in ≥25% of defecations
• Straining
• Lumpy/hard stools (Bristol Stool Scale 1-2)
• Sensation of incomplete evacuation
• Anorectal obstruction/blockage
• Manual maneuvers required
• <3 spontaneous bowel movements/week
• No loose stools without laxatives
• 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

Критерии исключения

• 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:

• Cardiopulmonary insufficiency
• Cerebrovascular diseases
• Psychiatric disorders
• Recent use (within 1 month) of confounding medications:

• Probiotics/prebiotics
• Antibiotics
• Laxatives (e.g., osmotic/stimulant agents)
• Prokinetics

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking Union Medical College Hospital — Пекин

Идентификаторы

NCT: NCT07065942 · I-23PJ993

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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