Kang Chen1, Hao Chen1, Marijke M Faas2, Bart J de Haan2, Jiahong Li1, Ping Xiao3, Hao Zhang1, Julien Diana4,5, Paul de Vos2, Jia Sun1,6. 1. State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, P. R. China. 2. Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 3. Institute of Clinical Medical Research, Affiliated Foshan Hospital of Sun Yat-sen University, Foshan, P.R. China. 4. Sorbonne Paris Cité, Université Paris Descartes, Paris, France. 5. 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. 6. School of Medicine, Jiangnan University, Wuxi, P.R. China.
Abstract
SCOPE: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.
SCOPE: 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 diabeticmice. METHODS AND RESULTS: Female nonobese diabeticmice 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. CONCLUSION: 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: S Mörkl; S Lackner; A Meinitzer; H Mangge; M Lehofer; B Halwachs; G Gorkiewicz; K Kashofer; A Painold; A K Holl; S A Bengesser; W Müller; P Holzer; S J Holasek Journal: Eur J Nutr Date: 2018-07-24 Impact factor: 5.614