Intestinal permeability, food antigens and the microbiome: a multifaceted perspective Original paper

What was reviewed?

This paper is a comprehensive narrative review that examined how intestinal permeability, food antigens, and the gut microbiome interact to shape immune responses and drive disease. The authors synthesized mechanistic, translational, and clinical evidence to describe the gut barrier as a dynamic, multi-layered system composed of the microbiota, mucus layer, epithelial cells, and mucosal immunity. The review emphasized that disease does not arise from a single defect, but from coordinated disruption across these layers, often triggered by diet, antibiotics, infections, and environmental exposures common in Westernized settings. The review focused specifically on immune-mediated and functional gastrointestinal conditions, positioning intestinal permeability as a central modulator rather than a passive consequence of inflammation.

Who was reviewed?

The review integrated findings from human cohorts, pediatric and adult patient populations, and multiple experimental models. Human data included individuals with celiac disease, non-celiac wheat sensitivity, food allergies, eosinophilic gastrointestinal disorders, irritable bowel syndrome, and inflammatory bowel disease. These clinical observations were interpreted alongside evidence from germ-free mice, antibiotic-exposed animals, epithelial cell culture systems, and dietary intervention models. This combination allowed the authors to link microbiota composition, epithelial tight junction regulation, and immune signaling pathways to clinically observable disease phenotypes.

What were the most important findings?

The review demonstrated that increased intestinal permeability acts as a gateway event that allows food antigens and microbial products to cross the epithelial barrier and activate immune responses. Major microbial associations included reduced abundance of short-chain fatty acid–producing Firmicutes such as Faecalibacterium prausnitzii and Clostridiales, alongside expansion of Proteobacteria including Enterobacteriaceae in inflammatory states. In allergic and eosinophilic disorders, dysbiosis favored taxa such as Streptococcus and Staphylococcus aureus, while protective genera such as Bifidobacterium, Lactobacillus, and select Clostridia were diminished. The review highlighted zonulin-mediated tight junction disassembly as a key mechanism linking gluten exposure, microbial signals, and permeability in celiac disease and non-celiac wheat sensitivity. Short-chain fatty acids, particularly butyrate and propionate, emerged as central microbial metabolites that reinforce barrier integrity, promote regulatory T cell differentiation, suppress Th2-skewed responses, and limit mast cell and eosinophil activation. The authors also emphasized how ultra-processed foods, emulsifiers, nanoparticles, and advanced glycation end products directly alter microbiota composition, thin the mucus layer, and weaken epithelial junctions, thereby amplifying immune reactivity to food antigens.

What are the greatest implications of this review?

For clinicians, this review reframes intestinal permeability as a modifiable driver of disease rather than a downstream marker of inflammation. It supports therapeutic strategies that restore microbial diversity, enhance short-chain fatty acid production, and reinforce epithelial barrier function as essential components of managing food-triggered and inflammatory conditions.