Effect of microencapsulated sodium butyrate on abdominal symptoms and carbohydrate metabolism in patients with type 2 diabetes: a randomized placebo-controlled trial.

Butyric acid, a short-chain fatty acid (SCFA) produced in the colon through bacterial fermentation of unabsorbed carbohydrates, plays a crucial role in maintaining gut health. Direct supplementation with butyric acid is not feasible because of its unpleasant taste and odor; hence, sodium butyrate is used as an alternative. Sodium butyrate has shown therapeutic potential, particularly for the treatment of irritable bowel syndrome (IBS), which is often associated with gut microbiota imbalance and a reduction in SCFA-producing bacteria. Supplementation with sodium butyrate alleviates gastrointestinal symptoms and improves metabolic regulation, especially in patients with type 2 diabetes, whose microbiota frequently lack sufficient butyrate-producing species. This study aimed to evaluate the effectiveness of oral supplementation with 1.5 g of sodium butyrate in reducing gastrointestinal symptoms in patients with type 2 diabetes and its impact on carbohydrate metabolism. This was a prospective, randomized, double-blind, placebo-controlled study. Fifty-two patients with type 2 diabetes who met the Rome IV criteria for IBS were randomized into two groups: one group received microencapsulated sodium butyrate (1.5 g/day) and the other received a placebo, for 12 weeks. During visits at weeks 0 and 12, anthropometric measurements, laboratory tests (including glycated hemoglobin [HbA1c] and Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] calculation), and a lactulose hydrogen breath test for small intestinal bacterial overgrowth (SIBO) were performed. The patients also completed a questionnaire to assess the severity of their gastrointestinal symptoms. After 12 weeks, the sodium butyrate group showed a significant reduction in gastrointestinal symptoms including abdominal pain (p = 0.001), diarrhea (p = 0.004), and bloating (p < 0.001). This group also demonstrated a decrease in the frequency of lactulose hydrogen breath test results, as well as reductions in body weight, HbA1c levels, and HOMA-IR index. No significant differences were observed in the placebo group. Our study demonstrated that sodium butyrate effectively alleviated gastrointestinal symptoms and improved carbohydrate metabolism. Notably, this trial demonstrated a direct reduction in lactulose hydrogen breath test results incidence with sodium butyrate supplementation. Further studies with larger cohorts are required to confirm these findings. This trial was retrospectively registered in the UK’s Clinical Study Registry under reference number ISRCTN10844715. Registration Date: 31/01/2025.