Fecal microbiota transfer from celiac patients induces immune and histopathological changes mirroring celiac disease in a rat model

Celiac disease (CD) is a chronic autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals, leading to intestinal inflammation and villous atrophy. Emerging evidence suggests that gut microbiota may play a pivotal role in CD pathogenesis. This study aimed to evaluate the immunological and histopathological effects of fecal microbiota transfer (FMT) from CD patients and healthy individuals into a rat model. After antibiotic-induced microbiota depletion, Wistar albino rats received FMT for three weeks, followed by histological and molecular analyses. Rats colonized with microbiota from CD patients exhibited significant weight loss (p < 0.001), increased intraepithelial lymphocyte infiltration (> 20 per high-power field), and villous atrophy with crypt hyperplasia, closely resembling CD-associated mucosal damage. Notably, histopathological analysis revealed a striking similarity between the duodenal biopsies of CD patients and the intestinal tissue of rats receiving FMT from CD donors. Additionally, proinflammatory cytokine levels, including IL-15, IL-21, TNF-α, and IFN-α mRNA expression in the duodenum, were significantly upregulated (p < 0.001). Serum levels of IL-17 and IFN-γ were also markedly elevated (p < 0.001) in these animals compared to controls. A strong correlation was observed between the severity of histopathological changes and cytokine expression, reinforcing the role of dysbiotic gut microbiota in CD-associated inflammation. These findings provide experimental evidence linking microbiota alterations to CD pathogenesis and suggest that modulating the gut microbiome may represent a potential therapeutic avenue for CD management.