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 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.