Effects of Butyrate Supplementation on Inflammation and Kidney Parameters in Type 1 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Type 1 diabetes is associated with increased intestinal inflammation and decreased abundance of butyrate-producing bacteria. We investigated the effect of butyrate on inflammation, kidney parameters, HbA1c, serum metabolites and gastrointestinal symptoms in persons with type 1 diabetes, albuminuria and intestinal inflammation. We conducted a randomized placebo-controlled, double-blind, parallel clinical study involving 53 participants randomized to 3.6 g sodium butyrate daily or placebo for 12 weeks. The primary endpoint was the change in fecal calprotectin. Additional endpoints were the change in fecal short chain fatty acids, intestinal alkaline phosphatase activity and immunoglobulins, serum lipopolysaccharide, CRP, albuminuria, kidney function, HbA1c, metabolites and gastrointestinal symptoms. The mean age was 54 ± 13 years, and the median [Q1:Q3] urinary albumin excretion was 46 [14:121] mg/g. The median fecal calprotectin in the butyrate group was 48 [26:100] μg/g at baseline, and the change was −1.0 [−20:10] μg/g; the median in the placebo group was 61 [25:139] μg/g at baseline, and the change was −12 [−95:1] μg/g. The difference between the groups was not significant (p = 0.24); neither did we find an effect of butyrate compared to placebo on the other inflammatory markers, kidney parameters, HbA1c, metabolites nor gastrointestinal symptoms. Twelve weeks of butyrate supplementation did not reduce intestinal inflammation in persons with type 1 diabetes, albuminuria and intestinal inflammation.

Sodium butyrate ameliorates diabetic retinopathy in mice via the regulation of gut microbiota and related short-chain fatty acids

“…De Groot et al [ 24 ] found that oral butyrate supplementation for 1 month did not result in any significant changes in adaptive or innate immunity, or in any of the other outcome variables in humans with longstanding T1D. Similarly, Tougaard et al [ 25 ] reported that 12 weeks of butyrate supplementation did not reduce intestinal inflammation in persons with T1D, albuminuria, and intestinal inflammation. Our data in mouse models of T1D seem to contrast previous studies showing no effect of butyrate in human T1D.…”

The Effect of Microbiome-Modulating Agents (MMAs) on Type 1 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Mean participant age ranged from 5.5 to 56 years, and T1D duration ranged from 1.5 to 30 years. Six studies implemented MMA supplementation for 3 months [30][31][32][33]35], with one study using less than 3 months [34] and three studies exceeding 3 months [29,34,37].…”

The Implication of Short-Chain Fatty Acids in Obesity and Diabetes

“… 87 , 88 Butyrate has received a lot of attention in recent studies because it seems to play a key role in the pathogenesis of obesity and diabetes. 81 , 89 - 91 …”

“…87,88 Butyrate has received a lot of attention in recent studies because it seems to play a key role in the pathogenesis of obesity and diabetes. 81,[89][90][91] Propionate and butyrate may contribute to metabolic health by activation of intestinal gluconeogenesis (IGN). 84,92 This activation permitted to explain of the anti-obesity and antidiabetic effects of dietary fibers.…”