PMID- 29018453 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240317 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 8 DP - 2017 TI - Inulin-Type Fructans Modulates Pancreatic-Gut Innate Immune Responses and Gut Barrier Integrity during Experimental Acute Pancreatitis in a Chain Length-Dependent Manner. PG - 1209 LID - 10.3389/fimmu.2017.01209 [doi] LID - 1209 AB - Acute pancreatitis (AP) is a common abdominal inflammatory disorder and one of the leading causes of hospital admission for gastrointestinal disorders. No specific pharmacological or nutritional therapy is available but highly needed. Inulin-type fructans (ITFs) are capable of modifying gut immune and barrier homeostasis in a chemistry-dependent manner and hence potentially applicable for managing AP, but their efficacy in AP has not been demonstrated yet. The current study aimed to examine and compare modulatory effects of ITFs with different degrees of fermentability on pancreatic-gut immunity and barrier function during experimentally induced AP in mice. BALB/c mice were fed short (I)- or long (IV)-chain ITFs supplemented diets for up to 3 days before AP induction by caerulein. Attenuating effects on AP development were stronger with ITF IV than with ITF I. We found that long-chain ITF IV attenuated the severity of AP, as evidenced by reduced serum amylase levels, lipase levels, pancreatic myeloperoxidase activity, pancreatic edema, and histological examination demonstrating reduced pancreatic damage. Short-chain ITF I demonstrated only partial protective effects. Both ITF IV and ITF I modulated AP-associated systemic cytokine levels. ITF IV but not ITF I restored AP-associated intestinal barrier dysfunction by upregulating colonic tight junction modulatory proteins, antimicrobial peptides, and improved general colonic histology. Additionally, differential modulatory effects of ITF IV and ITF I were observed on pancreatic and gut immunity: ITF IV supplementation prevented innate immune cell infiltration in the pancreas and colon and tissue cytokine production. Similar effects were only observed in the gut with ITF I and not in the pancreas. Lastly, ITF IV but not ITF I downregulated AP-triggered upregulation of IL-1 receptor-associated kinase 4 (IRAK-4) and phosphor-c-Jun N-terminal kinase (p-JNK), and a net decrease of phosphor-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) p65 (p-NF-kappaB p65) nuclear translocation and activation in the pancreas. Our findings demonstrate a clear chain length-dependent effect of inulin on AP. The attenuating effects are caused by modulating effects of long-chain inulin on the pancreatic-gut immunity via the pancreatic IRAK-4/p-JNK/p-NF-kappaBp65 signaling pathway and on prevention of disruption of the gut barrier. FAU - He, Yue AU - He Y AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. AD - School of Food Science and Technology, Jiangnan University, Wuxi, China. FAU - Wu, Chengfei AU - Wu C AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. AD - School of Food Science and Technology, Jiangnan University, Wuxi, China. FAU - Li, Jiahong AU - Li J AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. AD - School of Food Science and Technology, Jiangnan University, Wuxi, China. FAU - Li, Hongli AU - Li H AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. AD - School of Food Science and Technology, Jiangnan University, Wuxi, China. FAU - Sun, Zhenghua AU - Sun Z AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. AD - School of Food Science and Technology, Jiangnan University, Wuxi, China. FAU - Zhang, Hao AU - Zhang H AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. AD - School of Food Science and Technology, Jiangnan University, Wuxi, China. FAU - de Vos, Paul AU - de Vos P AD - Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands. FAU - Pan, Li-Long AU - Pan LL AD - Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China. AD - School of Medicine, Jiangnan University, Wuxi, China. FAU - Sun, Jia AU - Sun J AD - State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. AD - School of Food Science and Technology, Jiangnan University, Wuxi, China. AD - School of Medicine, Jiangnan University, Wuxi, China. LA - eng PT - Journal Article DEP - 20170926 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 EIN - Front Immunol. 2018 Apr 18;9:812. PMID: 29697703 PMC - PMC5622924 OTO - NOTNLM OT - antimicrobial peptides OT - dietary fibers OT - inflammation OT - pancreatic-intestinal immunity OT - signaling kinases OT - tight junction proteins EDAT- 2017/10/12 06:00 MHDA- 2017/10/12 06:01 PMCR- 2017/01/01 CRDT- 2017/10/12 06:00 PHST- 2017/06/20 00:00 [received] PHST- 2017/09/12 00:00 [accepted] PHST- 2017/10/12 06:00 [entrez] PHST- 2017/10/12 06:00 [pubmed] PHST- 2017/10/12 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2017.01209 [doi] PST - epublish SO - Front Immunol. 2017 Sep 26;8:1209. doi: 10.3389/fimmu.2017.01209. eCollection 2017.