Increased Bacterial Translocation in Gluten-Sensitive Mice Is Independent of Small Intestinal Paracellular Permeability Defect

Abstract

Aim We investigated whether treatment with gliadin induces a paracellular permeability defect that enhances bacterial translocation to mesenteric lymph nodes (MLN) via resident dendritic cells (DC) expressing TLR-2 or 4 in HCD4/HLA-DQ8 transgenic mice. Methods HLA-DQ8 transgenic mice were sensitized and subsequently gavaged with gliadin, in the presence or absence of AT1001 (paracellular permeability inhibitor). Non-sensitized mice were gavaged with indomethacin (permeability inducer) or rice cereal. CD11c and CD103 (DC markers) and TLR-2 and 4 were investigated by immunostaining. Intestinal permeability was assessed by paracellular flux of 51Cr-EDTA in Ussing chambers. Bacterial translocation to MLN was performed by plate counting on aerobic and anaerobic conditions. Results In gliadin-treated mice, both 51Cr-EDTA flux in jejunal mucosa and aerobic and anaerobic bacterial counts in MLN were increased (p < 0.05) compared to indomethacin-treated mice and controls. The inhibitor AT1001 normalized 51Cr-EDTA flux, but had no effect on bacterial translocation in gliadin-treated mice. In addition, changes in mucosal DC marker distribution such as increased (p < 0.05) trans-epithelial CD103+ cells and reduction (p < 0.05) of CD11c immunostaining were detected in gliadin-treated mice. Moreover, changes in DC markers and TLR-2 or 4 immunophenotypes were not associated. Conclusions Pharmacological restoration of paracellular permeability was not sufficient to prevent bacterial translocation in gluten-sensitive mice. We hypothesize that transcellular mechanisms involving CD103+DC and CD11c+DC may explain in gluten-sensitive HCD4/HLA-DQ8 transgenic mice the sustained increased bacterial translocation observed in the absence of a significant inflammatory response.

Role of a Bacillus subtilis Direct-Fed Microbial on Digesta Viscosity, Bacterial Translocation, and Bone Mineralization in Turkey Poults Fed with a Rye-Based Diet

“…Particularly, the levels of LPS, a component of Gram-negative bacteria, are increased in the portal and/or systemic circulation with impaired gut epithelial integrity and dysbacteriosis ( 37 ). Strong evidence suggests that pathogen-derived compounds from the gut have a major role and modulating effect on liver diseases and chronic inflammation ( 38 , 39 ). Diet ingredients, integrity of the gut epithelium, immune defense in the gut and in the liver, as well as the composition of the microbiome in the intestinal tract all appear to play an integrated role in the maintenance of health and balance in the gut–liver axis ( 40 ).…”

Rye Affects Bacterial Translocation, Intestinal Viscosity, Microbiota Composition and Bone Mineralization in Turkey Poults

“…No. 89429–342 Suwanee, GA 30024) to evaluate total counts of Enterobacteriaceae per gram of tissue as has been previously described [ 11 , 26 , 27 ].…”

Novel Role of the Serine Protease Inhibitor Elafin in Gluten-Related Disorders

“…Two sections of jejunum from each mouse were assessed. Tissue conductance (the passive permeability to ions) and mucosal-to-serosal flux of the paracellular probe 51 Cr-EDTA were used to assess barrier function and paracellular permeability as previously described (30). 51 Cr-EDTA flux was calculated as the average over a 2-h period and expressed as %hot/cm 2 /h.…”