Crystal type, chain length and polydispersity impact the resistant starch type 3 immunomodulatory capacity via Toll-like receptors.

Food ingredients that can activate and improve immunological defense, against e.g., pathogens, have become a major field of research. Resistant starches (RSs) can resist enzymes in the upper gastrointestinal (GI) tract and induce health benefits. RS-3 physicochemical characteristics such as chain length (DP), A- or B-type crystal, and polydispersity index (PI) might be crucial for immunomodulation by activating human toll-like receptors (hTLRs). We hypothesize that crystal type, DP and PI, alone or in combination, impact the recognition of RS-3 preparations by hTLRs leading to different RS-3 immunomodulatory effects. We studied the activation of hTLR2, hTLR4, and hTLR5 by 0.5, 1 and 2 mg/mL of RS-3. We found strong activation of hTLR2-dependent NF-kB activation with PI <1.25, DP 18 as an A- or B-type crystal. At different doses, NF-kB activation was increased from 6.8 to 7.1 and 10-fold with A-type and 6.2 to 10.2 and 14.4-fold with B-type. This also resulted in higher cytokine production in monocytes. Molecular docking, using amylose-A and B, demonstrated that B-crystals bind hTLR2 promoting hTLR2-1 dimerization, supporting the stronger effects of B-type crystals. Immunomodulatory effects of RS-3 are predominantly hTLR2-dependent, and activation can be tailored by managing crystallinity, chain length, and PI.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paul de Vos reports financial support was provided by Dutch Research Council. A.A.C.M. Lizette Oudhuis reports a relationship with Royal Avebe that includes: employment. Hans Leemhuis reports a relationship with Royal Avebe that includes: employment. This research was performed in the public-private partnership ‘CarboBiotics’ coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl). CarboBiotics is financed by participating industrial partners Royal Avebe U.A., FrieslandCampina Nederland B.V. and Nutrition Sciences N.V. and allowances of the Dutch Research Council (NWO).
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