Dietary fibers have been shown to exert immune effects via interaction with pattern recognition receptors (pRR) such as toll-like receptors (tLR) and nucleotide-binding oligomerization domain (noD)like receptors. Pectin is a dietary fiber that interacts with PRR depending on its chemical structure. Papaya pectin retains different chemical structures at different ripening stages. How this influence PRR signaling is unknown. The aim of this work was to determine how ripening influences pectin structures and their ability to interact with TLR2, 3, 4, 5 and 9, and NOD1 and 2. It was evaluated the interaction of the water-soluble fractions rich in pectin extracted from unripe to ripe papayas. The pectin extracted from ripe papayas activated all the TLR and, to a lesser extent, the NOD receptors. The pectin extracted from unripe papayas also activated TLR2, 4 and 5 but inhibited the activation of TLR3 and 9. The differences in pectin structures are the higher methyl esterification and smaller galacturonan chains of pectin from ripe papayas. Our finding might lead to selection of ripening stages for tailored modulation of pRR to support or attenuate immunity. Dietary fibers (DF) commonly represent a wide variety of polysaccharides originating from fruits, vegetables, whole grains and legumes with several health benefits. Such benefits include slow gastric empty 1 and improve physical bowel function 2. Besides the physical benefits, DF can also interact directly with intestinal cells and/or the immune cells from the mucosa 3-5. It is not just the direct effects of DF on cells may trigger immune modulations 6 but also the DF fermentation in the gut 7,8. The direct interaction of DF with the intestinal cells may occur through pattern recognition receptors (PRR) 9. The PRR are germline-encoded sensors expressed in intestinal epithelial cells and gut immune cells. PRR are the key receptors responsible for the recognition of exogenous molecules by the host 5,9. Toll-like receptors (TLR) are a family of PRR that play a central role in the activation of innate immunity 10 and have been shown to be involved in DF-induced immune signaling as described below. The immune response mediated by TLR activation requires the recruitment of myeloid differentiation primary response protein 88 (MyD88) adaptor and the translocation of NF-κB to the nucleus 10. Only TLR3 NF-κB activation is not dependent on MyD88 protein which is mediated by TIR domain-containing adapter inducing IFN-β (TRIF), though 11. The interactions between wide variety of DF and TLR have been extensively studied. DF have a complex and heterogeneous structure and some DF activate TLR to different extents 12 while other DF (such as pectin) seem to block TLR signaling and attenuate intestinal inflammation 6. Nucleotide-binding oligomerization domains (NOD) have also been shown to be influenced by DF, such as β2 → 1-fructans. NOD are proteins responsible for the recognition of intracellular bacteria 10. Through this signaling via PRR, DF have been shown to mediate several ho...

No abstract

Scope Intestinal mucositis is a common side effect of the chemotherapeutic agent doxorubicin, which is characterized by severe Toll‐like receptor (TLR) 2‐mediated inflammation. The dietary fiber pectin is shown to prevent this intestinal inflammation through direct inhibition of TLR2 in a microbiota‐independent manner. Recent in vitro studies show that inhibition of TLR2 is determined by the number and distribution of methyl‐esters of pectins. Therefore, it is hypothesized that the degree of methyl‐esterification (DM) and the degree of blockiness (DB) of pectins determine attenuating efficacy on doxorubicin‐induced intestinal mucositis. Methods and Results Four structurally different pectins that differed in DM and DB are tested on inhibitory effects on murine TLR2 in vitro, and on doxorubicin‐induced intestinal mucositis in mice. These data demonstrate that low DM pectins or intermediate DM pectins with high DB have the strongest inhibitory impact on murine TLR2‐1 and the strongest attenuating effect on TLR2‐induced apoptosis and peritonitis. Intermediate DM pectin with a low DB is, however, also effective in preventing the induction of doxorubicin‐induced intestinal damage. Conclusion These pectin structures with stronger TLR2‐inhibiting properties may prevent the development of doxorubicin‐induced intestinal damage in patients undergoing chemotherapeutic treatment with doxorubicin.

Introduction: Pectins have anti-inflammatory properties on intestinal immunity through direct interactions on Toll-like receptors (TLRs) in the small intestine or via stimulating microbiota-dependent effects in the large intestine. Both the degree of methyl-esterification (DM) and the distribution of methyl-esters (degree of blockiness; DB) of pectins contribute to this influence on immunity, but whether and how the DB impacts immunity through microbiota-dependent effects in the large intestine is unknown. Therefore, this study tests pectins that structurally differ in DB in a mouse model with Citrobacter rodentium induced colitis and studies the impact on the intestinal microbiota composition and associated attenuation of inflammation. Methods and Results: Both low and high DB pectins induce a more rich and diverse microbiota composition. These pectins also lower the bacterial load of C. rodentium in cecal digesta. Through these effects, both low and high DB pectins attenuate C. rodentium induced colitis resulting in reduced intestinal damage, reduced numbers of Th1-cells, which are increased in case of C. rodentium induced colitis, and reduced levels of GATA3 + Tregs, which are related to tissue inflammation. Conclusion: Pectins prevent C. rodentium induced colonic inflammation by lowering the C. rodentium load in the caecum independently of the DB.

No abstract