Original Research ARTICLE
Dietary fiber pectin directly blocks Toll-like receptor 2-1 and prevents doxorubicin induced ileitis
- 1Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Center Groningen, Netherlands
- 2Laboratory of Food Chemistry, Wageningen University & Research, Netherlands
- 3Faculty of Mathematics and Natural Sciences, Neuroendocrinology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Netherlands
- 4Agrifirm Plant BV, Netherlands
- 5Animal Nutrition Group, Wageningen University & Research, Netherlands
- 6Nuscience Group (Belgium), Belgium
- 7DSM (Netherlands), Netherlands
Dietary carbohydrate fibers are known to prevent immunological diseases common in Western countries such as allergy and asthma but the underlying mechanisms are largely unknown. Until now beneficial effects of dietary fibers are mainly attributed to fermentation products of the fibers such as anti-inflammatory short chain fatty acids. Here, we found and present a new mechanism by which dietary fibers can be anti-inflammatory: a commonly consumed fiber, pectin, blocks innate immune receptors. We show that pectin binds and inhibits, Toll-like receptor 2 (TLR2) and specifically inhibits the proinflammatory TLR2-TLR1 pathway while the tolerogenic TLR2-TLR6 pathway remains unaltered. This effect is most pronounced with pectins having a low degree of methyl esterification (DM). Low DM pectin interact with TLR2 through electrostatic forces between non-esterified galacturonic acids on the pectin and positive charges on the TLR2 ectodomain, as confirmed by testing pectin-binding on mutated TLR2. The anti-inflammatory effect of low DM pectins was first studied in human dendritic cells and mouse macrophages in vitro and was subsequently tested in vivo in TLR2 dependent ileitis in a mouse model. In these mice, ileitis was prevented by pectin administration. Protective effects were shown to be TLR2-TLR1-dependent and independent of the short chain fatty acids (SCFA) produced by the gut microbiota. These data suggest that low DM pectins as a source of dietary fiber can reduce inflammation through direct interaction with TLR2-TLR1 receptors.
Keywords: Dietary Fiber, Toll-Like Receptor 2, pectin, Ileitis, degree of methyl esterification.
Received: 07 Nov 2017;
Accepted: 12 Feb 2018.
Edited by:Zorica D. Juranic, Institute of Oncology and Radiology of Serbia, Serbia
Reviewed by:Julien DIANA, Institut National de la Santé et de la Recherche Médicale (INSERM), France
Kohji Kitaguchi, Gifu University, Japan
Copyright: © 2018 Sahasrabudhe, Beukema, Tian, Troost, Scholte, Bruininx, Bruggeman, van den Berg, Scheurink, Schols, Faas and De Vos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Neha M. Sahasrabudhe, University Medical Center Groningen, Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, Groningen, Netherlands, firstname.lastname@example.org