New prebiotics from rice bran ameliorate inflammation in murine colitis models through the modulation of intestinal homeostasis and the mucosal immune system

Abstract

Background. Enzyme-treated rice fiber (ERF) is a recently developed prebiotic product made from rice bran by heat-resistant amylase, protease and hemicellulase treatment. Although the detailed mechanism of inflammatory bowel disease (IBD) is still unclear, the role of the resident luminal bacteria and its interaction on the mucosal barrier seem to be an important factor in the development of IBD and its chronicity. With the objective of manipulating the intestinal microbiota in IBD, this study was carried out to evaluate the effects of ERF on IBD with using experimental colitis models. Methods. Three colitis models were used and they were induced by the oral administration of dextran sodium sulfate in male Sprague–Dawley rats or BALB/c mice and transferring CD4+ CD45RB^high T cells to female SCID mice, sequentially their CD4+ T cells were retransferred to new SCID mice. The evaluation included the measurement of body weight, spleen weight, colon length, histological examination, serum and mucosal cytokine (tumor necrosis factor-alpha (TNF-α), an interferon-gamma (IFN-γ), interleukin-12 p70 (IL-12p70), IL-1β, IL-6, IL-4) analysis, mucosal serotonin (5HT), and organic acid production and a microbiota analysis of the cecal contents. The characteristics of T cell surface markers including CD4, CD69, CD45RB of spleen and mesenteric lymph nodes (MLN) were also analyzed. In addition, the effects of ERF on the change in the induction of dendritic cells (DCs) were evaluated. Results. The preventive effect of ERF on colitis was significantly superior to that of raw material rice bran or control group. An overexpression of inflammatory cytokine production was attenuated by ERF treatment, which was accompanied with a decrease in both the colonic mucosal damage and 5HT production. Furthermore, ERF significantly attenuated the T cell activation (CD4+CD69+) of spleen and MLN, and this characteristic was inherited by the retransferred mice. ERF significantly suppressed the growth of Clostiridium, and increased short-chain fatty acids (acetate, propionate and butyrate) content in colitis. The relatively hydrophilic fraction of ERF (ethanol–methanol soluble fraction) is therefore considered to have a potent ability to attenuate the induction of DCs. Conclusion. A new prebiotic, ERF, reduced inflammation by modulating the colonic environment and regulating immune cell differentiation. Although a more detailed study is required, this study showed the promising anti-inflammatory effects of an adjunctive prebiotic treatment for IBD.

Key Words::

• Dietary fiber
• inflammatory bowel disease
• microbiota
• mucosal immunology
• short-chain fatty acids

Acknowledgments

We are most grateful to Dr Satoru Mizutani (Kirin Holdings Co., Ltd.) for encouragement and Ms Kumiko Ikado, Mr Shintaro Ichikawa, Ms Megumi Andoh, Ms Fumi Yoshinaka, and Ms Kei Koike (Kirin Holdings Co., Ltd) for their excellent technical assistance.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.