Development and Validation of a Gliadin Induced Intestinal Enteropathy Rat Model of Non-Celiac Gluten Sensitivity

Author(s): Walaa Albenayan, Nabil Alruwaili, José Rodrigo Pauli, Andrella King, Mattia Migliore and Iman Zaghloul

Background: Non-celiac gluten sensitivity (NCGS) is a syndrome that is related to the ingestion of gluten-containing food. In the current study we developed and validated a NCGS rat model. Materials and Methods: Wistar rats were divided into 2 groups: control group (receiving 0.02 M acetic acid solution) and gliadin group (receiving 1.5 mg/g of body weight of gliadin in acetic acid solution). Rats received its treatment by intra-gastric gavage on postnatal day 2, then three times a week for 6 weeks. Animals were assessed for weight changes, intestinal permeability, histology, inflammatory cytokines, and anti-gliadin antibodies (AGA). Intestinal permeability was evaluated 24 h prior to sacrifice by administering a lactulose/mannitol solution (500/250 mg/kg respectively), and collecting urine for 24 h. For histological examination, small intestines were collected, fixed, and stained with hematoxylin and eosin. Intestinal gene expression of cytochrome P450 (CYP 3a62, CYP 3a9/18) and uptake transporters, breast cancer resistance protein (ABCG2), and P-glycoprotein (MDR1a) were evaluated using qRT-PCR. Blood was collected for measurement of totalanti-gliadin antibodies (AGA), anti-gliadin immunoglobulins A and M (AGA-IgA and AGA-IgM), and pro-inflammatory cytokines. Results: As compared to control, the gliadin group had lower body weight, increased intestinal permeability (p<0.05); mild villous atrophy, increased intraepithelial lymphocytes, mild inflammation; increases in total AGA and AGA-IgM, increased gene expression of pro-inflammatory cytokines, IL-6, TNF-α, and IFN-γ, by 94%, 33%, and 46% (p < 0.05) and altered gene expressions of CYP450 and transporters. Conclusions: This model closely mimics the pathological and inflammatory characteristics of NCGS, and could be used to test new pharmacological treatments for this syndrome.