Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function and microbiota homeostasis
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Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here we aimed to compare modulatory effects of inulin-type fructans (ITFs), natural chicory root -derived soluble dietary fibers with different degrees of fermentability, on T1D development in non-obese diabetic (NOD) mice.
Female NOD mice were weaned to long-or short-chain ITFs [ITF(l) or ITF(s), 5 weight-% in the diet] 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 lowered the incidence of T1D. ITF(l) promoted modulatory T cell responses, as evidenced by increased CD25+Foxp3+CD4+ Treg cells, decreased IL17A+CD4+ Th17 cells and modulated cytokine production profile in the pancreas, spleen and colon. Furthermore, ITF(l) suppressed NLRP3-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 CRAMP as well as SCFA production were enhanced by ITF(l). Next-generation sequencing analysis revealed that ITF(l) enhanced Firmicutes/Bacteroidetes ratio to an anti-diabetogenic 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.