Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects

Abstract

BackgroundGut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism.MethodsHealthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment.ResultsOral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 µmol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 ± 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 ± 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 ± 2.4 versus metabolic syndrome subjects to 1.2 ± 4.1).ConclusionsOral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus.

Alteration of gut microbiota by a Westernized lifestyle and its correlation with insulin resistance in non‐diabetic Japanese men

“…On estimating the role of Odoribacter in insulin sensitivity, it was found that Odoribacter produced butyrate 34 . Oral butyrate treatment was reported to improve insulin sensitivity in healthy lean men 35 . In the present study, there was no difference in the fecal butyrate concentration between the two groups, and thus butyrate might not have been the main contributor to the differences in the insulin resistance.…”

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“…Additionally, blood lipids (triglycerides, cholesterol, and total fatty acids) were decreased. However, when oral butyrate was given for 4 weeks to human subjects, only lean subjects showed an increase in insulin sensitivity whereas obese insulin resistant subjects did not show any effect …”

“…However, when oral butyrate was given for 4 weeks to human subjects, only lean subjects showed an increase in insulin sensitivity whereas obese insulin resistant subjects did not show any effect. 81 One of the butyrate producing bacteria of particular interest for the use as probiotic is the anaerobic, Gram-positive E hallii, belong-…”

Gut microbiota: a promising target against cardiometabolic diseases

“…Nevertheless, it remains uncertain whether changes in butyrate caused this improvement in insulin sensitivity, as the study was not designed to evaluate a causal link [70]. Noteworthy, four weeks of oral butyrate supplementation to metabolic syndrome subjects showed no effect on insulin sensitivity [71]. The absence of effect could be due to the oral ingestion of butyrate.…”