Immunomodulatory Effects of Lactobacillus casei Administration in a Mouse Model of Gliadin‐Sensitive Enteropathy

Abstract

Coeliac disease (CD) is a very common food‐sensitive enteropathy, which is triggered by gluten ingestion and is mediated by CD4+ T cells. In addition, alterations in the intestinal microbiota that is normally involved in the homeostasis of GALT (gut‐associated lymphoid tissue) seem to play a role in CD. In accordance with these findings, we previously reported that Lactobacillus casei can induce a strong enhancement of the T cell‐mediated response to gliadin without inducing enteropathy. In this study, we analysed the effects of L. casei administration in a mouse model of gliadin‐induced villous damage that was recently developed and involves the inhibition of cyclo‐oxygenase (COX) activities in gliadin‐sensitized HLA‐DQ8 transgenic mice. To address the issue, we assessed the weight loss, the intestinal cytokine pattern, the density of CD25+ cells and morphometry of the gut mucosa. We confirmed that COX inhibition in sensitized mice caused villus blunting, dysregulated expression of tumour necrosis factor (TNF)‐α and reduced gliadin‐specific IL‐2 production. Notably, the administration of probiotic strain induced a complete recovery of villus blunting. This finding was associated with a delay in weight decrease and a recovery of basal TNF‐α levels, whereas the numbers of CD25+ cells and the levels of IL‐2 remained unchanged. In conclusion, our data suggest that the administration of L. casei can be effective in rescuing the normal mucosal architecture and GALT homeostasis in a mouse model of gliadin‐induced enteropathy.

Intestinal Microbiota and Probiotics in Celiac Disease

“…This effect could apparently contribute to an improvement in the gut barrier function and prevent the translocation of gliadin to the lamina propria (48). Similar to previous work, L. casei ATCC 9595 administration was able to significantly reduce the levels of TNF-␣ and to repair the intestinal injury induced by gliadin in HLA-DQ8 transgenic mice under indomethacin treatment (49).…”

Type 1 Diabetes and Celiac Disease: Clinical Overlap and New Insights into Disease Pathogenesis

“…These studies show that intestinal flora is capable of altering mucosal immune cell activity in a model of CD. Further investigation showed supplemental Lactobacillus casei not only modifies inflammatory signaling, but also induced complete recovery of villous blunting and delayed weight loss in a mouse model of gliadin-induced villous damage [68]. These results provide further evidence that the intestinal microbiome has complex effects on the host's immune function and disease states.…”

“…Similar to studies in models of T1D, introduction of nonpathogenic, commensal microbes modifies intestinal inflammatory signaling and response to gliadin [66-68]. In another similarity with T1D, exposure to pathogenic bacteria increases intestinal permeability, leading to greater translocation of gliadin fragments into the lamina propria [69].…”

Generation of food-grade recombinant Lactobacillus casei delivering Myxococcus xanthus prolyl endopeptidase

“…Nevertheless for our purpose the mice are good candidates due to their shorter lifespan, the advances in their genetic manipulation and the ability to radically alter their intestinal microbiota. Furthermore, a T-cell adjuvant effect of L. casei has been demonstrated in a mouse model of gluten sensitivity (D’Arienzo et al 2008), and the potential of L. casei to reduce gliadin-specific enteropathy has been observed in this same mouse model (D’Arienzo et al 2011). In fact, administration of L. casei reduces villous atrophy and the abnormal homeostasis of the gut mucosa.…”