Bifidobacteria and Celiac Disease: Mechanisms of Probiotic Action in Reducing Gluten-Induced Cytotoxicity and Inflammation

Abstract

Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten peptides present in the diets of genetically susceptible individuals, leading to a range of intestinal and extra-intestinal manifestations. Although managed by a gluten-free diet (GFD), symptoms persist in 30%-50% of treated individuals despite apparent dietary compliance. Accordingly, the present review explores how bifidobacteria may mediate cytotoxic and proinflammatory responses induced by gluten-derived peptides, contributing to the modulation of CD symptoms. Experimental in vitro studies, primarily using Caco-2 cells and immune cell models, have shown that strains such as Bifidobacterium longum IATA-ES1, Bifidobacterium lactis, Bifidobacterium bifidum IATA-ES2, and B. lactis Natren Life Start super strain (NLS-SS) can induce COX-1 expression and reduce COX-2, inhibit zonulin release, degrade gliadin-derived peptides, and suppress CXCR3 mRNA expression and inflammatory mediators (e.g., TNF-α, IFN-γ, NF-κB, and IL-1β). Animal studies have provided evidence of immunomodulatory effects and improved mucosal responses, while human clinical trials have reported improvements in gastrointestinal symptoms and inflammatory markers with probiotic interventions. These findings support the potential of Bifidobacterium spp. as adjunctive agents in CD management. However, further clinical research is needed to clarify strain-specific effects and confirm the translational relevance of these mechanisms.

Keywords: celiac disease; gluten; mechanisms; probiotics.

FIGURE 1

Flowchart of the article selection process.

FIGURE 2

Possible pathways of Bifidobacterium spp. action in CD, including the mechanisms of action. (1) induction of COX‐1 expression in Caco‐2 cells and reduction of COX‐2 expression, ensuring intestinal mucosa integrity, (2) decreased zonulin activation and inhibition of CXCR3 mRNA expression, preventing tight junction breakdown, (3) hydrolysis of gliadin‐derived peptides, preventing excess gluten peptides in the intestinal lumen, (4) and (5) control of the Th1 response and reduction of TNF‐α, IFN‐γ, NF‐kB, and IL‐1β production, (6) alteration of the dysregulated intestinal microbiota in CD.

FIGURE 3

Zonulin release mechanism from gluten ingestion: (1) Specific gliadin peptides, (2) CXCR3, (3) PKC‐α, (4) non‐self antigens.

FIGURE 4

Gliadins‐derived peptides after gastrointestinal digestion with Bifidobacterium spp. Adapted from Laparra and Sanz laparra.[41]