A diet enriched in omega-3 PUFA and inulin prevents Type 1 Diabetes by restoring gut barrier integrity and immune homeostasis in NOD mice. Omega3_PUFA_Inulin

The integrity of the gut barrier is fundamental to regulate the crosstalk between the microbiota and the immune system and to prevent inflammation and autoimmunity at the intestinal level but also in organs distal from the gut such as the pancreatic islets. In support to this idea, we recently demonstrated that breakage of gut barrier integrity leads to activation of islet-reactive T cells and triggers autoimmune Type 1 Diabetes (T1D). In the NOD mice, the spontaneous model of T1D, there are alterations of the gut barrier integrity that specifically affect structure and composition of the mucus layer but it is yet to be determined whether there is a causal link between breakage of the gut barrier integrity and occurrence of autoimmune T1D. Here we restored gut barrier integrity in NOD mice through administration of an anti-inflammatory diet (AID- enriched in soluble fibers and omega 3-PUFA) and tested the effect on GB integrity and prevention of T1D. The restoration of GB integrity and immune homeostasis were associated with enhanced concentrations of anti-inflammatory metabolites of the n-6/n-3 PUFA and arachidonic pathways and modifications of the microbiome profile with increased relative abundance of mucus-regenerating bacterial species such as Akkermansia muciniphila and Akkermansia glycaniphila.