Butyrate modulates TGF-β1 generation and function: Potential renal benefit for Acacia(sen) SUPERGUM™ (gum arabic)?

Anecdotal evidence suggests that high fibre supplementation of dietary intake may have health benefits in renal disease related to alterations in circulating levels of short-chain fatty acids. The aim of the study was to examine the hypothesis that dietary manipulation may increase serum butyrate and thus have potential beneficial effects in renal disease. We examined the effect of dietary supplementation with a gum arabic sample of standardized molecular characteristics, Acacia(sen) SUPERGUM™ EM2 (SUPERGUM™), on systemic levels of butyrate in normal human subjects. In an in vitro study, we also examined the potential role of butyrate in modifying the generation of the profibrotic cytokine transforming growth factor-beta (TGF-β1) by renal epithelial cells. Following 8 weeks of dietary supplementation with 25 g/day of SUPERGUM™, there was a two-fold increase in serum butyrate (n=7, P=0.03). In vitro work demonstrated that exposure of renal epithelial cells to elevated concentrations of butyrate suppressed both basal and stimulated TGF-β1 synthesis. The action of butyrate was mediated by suppression of the extracellular signal-regulated kinase/mitogen-activated protein kinase signalling pathway. In addition, butyrate exposures reduced the response of renal epithelial cells to TGF-β1 as assessed by luciferase activity of a TGF-β-responsive reporter construct. Attenuation of TGF-β1 signalling was associated with reduced phosphorylation of Smad 3 and decreased trafficking of TGF-β1 receptors into signalling, non-lipid raft-associated membrane fractions. In conclusion, the data demonstrate that dietary supplementation with SUPERGUM™ increased serum butyrate, which at least in vitro has beneficial effects on renal pro-fibrotic cytokine generation.