title: Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis.
abstract: Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here, we aim to compare modulatory effects of inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on T1D development in nonobese diabetic mice.
  
  
  
  Female nonobese diabetic mice were weaned to long- and short-chain ITFs [ITF(l) and ITF(s), 5%] supplemented diet up to 24 weeks. T1D incidence, pancreatic-gut immune responses, gut barrier function, and microbiota composition were analyzed. ITF(l) but not ITF(s) supplementation dampened the incidence of T1D. ITF(l) promoted modulatory T-cell responses, as evidenced by increased CD25+Foxp3+CD4+regulatory T cells, decreased IL17A+CD4+Th17 cells, and modulated cytokine production profile in the pancreas, spleen, and colon. Furthermore, ITF(l) suppressed NOD like receptor protein 3 caspase-1-p20-IL-1β inflammasome in the colon. Expression of barrier reinforcing tight junction proteins occludin and claudin-2, antimicrobial peptides β-defensin-1, and cathelicidin-related antimicrobial peptide as well as short-chain fatty acid production were enhanced by ITF(l). Next-generation sequencing analysis revealed that ITF(l) enhanced Firmicutes/Bacteroidetes ratio to an antidiabetogenic balance and enriched modulatory Ruminococcaceae and Lactobacilli.
  
  
  
  Our data demonstrate that ITF(l) but not ITF(s) delays the development of T1D via modulation of gut-pancreatic immunity, barrier function, and microbiota homeostasis.
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, P. R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marijke M
authors.initials: MM
authors.lastname: Faas
authors.affiliation: Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bart J
authors.initials: BJ
authors.lastname: de Haan
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, P. R. China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Clinical Medical Research, Affiliated Foshan Hospital of Sun Yat-sen University, Foshan, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Sorbonne Paris Cité, Université Paris Descartes, Paris, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1151, Institut Necker-Enfants Malades (INEM), Centre National de la Recherche ITF(l)enctifique, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Diana
authors.affiliation: Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, P. R. China.|School of Medicine, Jiangnan University, Wuxi, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000382:microbiology / Q000517:prevention & control*; D004043:Dietary Fiber / Q000494:pharmacology*; D005260:Female; D005630:Fructans / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D007444:Inulin / Q000737:chemistry / Q000494:pharmacology; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects
chemical_list: D016207:Cytokines; D004043:Dietary Fiber; D005630:Fructans; D007444:Inulin
keywords: Barrier integrity; Dietary fibers; Gastroentero pancreatic regulation; Gut microbiota homeostasis; Immunomodulation; Nutritional intervention; Pancreatic-gut immunity; Type 1 diabetes pathophysiology
  