Experimental studies on dietary fibers: Pattern recognition receptor interactions

Increased frequency of immunological disorders in western society has been described to be because of lower consumption of dietary fibers. The immunomodulatory effects of dietary fibers can be through the fermentation by intestinal microbiota, producing immune-regulatory SCFAs. However, SCFA independent immunomodulatory effects have also been described through direct interaction with immune receptors. Pattern recognition receptors (PRRs) are the first line of immune receptors expressed in intestinal lumen. In this thesis we studied the immunomodulatory effects of dietary fibers through interaction with PRRs. Cereal grain dietary fibers like β-glucan, arabinoxylan and pectin were studied for their interaction with PRRs like Dectin-1 and Toll-like receptors (TLRs). We have shown that dietary β-glucan can have increased immune stimulation after digestion by microbiota derived enzymes through activation of Dectin-1. Arabinoxylan, a cereal grain dietary fiber having structural similarity with β-glucan, also activated Dectin-1 receptor. We also demonstrated that β-glucan can synergistically activate Dectin-1 and TLR4, which leads to differential activation by soluble and particulate β-glucan. To further illustrate the structure to effector function of dietary fibers, we studied lemon pectin having different degrees of methyl esterification (DM). We have shown that low DM pectin can bind and inhibit TLR2 which results in anti-inflammatory effect of pectin in chemotherapy induced intestinal inflammations. The binding of pectin with TLR2 is through electrostatic interactions and specific for low DM pectin. These different mechanisms of immunomodulatory effects of dietary fibers can be used for feed/ food applications and can be instrumental to reduce immunological disorders.