Context-dependent roles of the gut microbiome in food allergy tolerance versus sensitization

Exposure to food antigens that can trigger aberrant type-2 immunity is ubiquitous. However, only a subset of individuals develops allergy, implicating environmental drivers of sensitization, among which diet- and antibiotic-induced changes in intestinal microbiome activity stand out for their ability to alter host-microbe interactions at the gut mucosa. While efforts seek microbial signatures and microbiome-based therapies, the same microbes or pathways may foster either tolerance or sensitization depending on host and environmental context, which must be considered when designing interventions. We synthesize recent molecular insights into mucosal host-microbiome crosstalk, focusing on regulatory T cells, the colonic mucus barrier, and host immunoglobulins (IgA and IgE). Using examples of microbiome functional duality in which diet-driven altered microbial activities and secreted molecules such as lipopolysaccharides and flagellins yield opposing effects, we discuss the context-dependent mechanisms by which microbes either protect against or promote food allergy.