Gut microbial composition modulates food-specific CD4+ T cells in food allergy

Keywords

• Food allergy

• Gut microbiome

• Food-specific T cells

• Regulatory T cells

Main Findings

Food allergy has been related with alterations or changes in the gut microbiome. Some studies have found that dysbiosis in gut microbiome could lead to allergic sensitization, for example. It has also been seen that different abundance in strains from the gut have an impact in the reactivity threshold of patients with similar characteristics. Weingarden et al. tried to investigate the contribution of the gut microbiome to CD4 responses in allergy. They utilize mice from two different vendors and could show that these mice had significantly different responses to allergic sensitization, which could be related to differences in gut microbiome composition

Cytometry analysis revealed non-significant differences in the allergen specific CD4+ effector T cells or regulatory T cells (Treg) in secondary lymphoid organs. However, Jax animals showed higher proportions of allergen specific CD4+ T cells and lower Treg cells, in the small intestine lamina propria thanTac mice. This correlated with severe allergic reactions in Tac mice. Tac mice also exhibited higher levels of allergen specific IgE, more gut permeability, and higher levels of mast cells.

To show the contribution of the microbiome to this effect, mice from both vendors were co-housed after sensitization. When OVA gavages were administered as a challenge, the percentage of Jax animals experiencing severe symptoms was increased when co-housed with Tac animals compared to Jax animals alone. Furthermore, mice originally from Jax that had been co-housed with Tac mice acquired fecal bacterial communities that more closely resembled those from Tac mice than animals from Jax.

The authors conclude that microbial composition in Tac mice promotes increased gut permeability and uptake of food allergen. In turn, this may either limit the development of food-specific Treg cells directly or could promote degranulation and expansion of mucosal mast cells. This increased mast cell population could in turn suppress intestinal Treg cells. Ultimately, these changes could result in increased food allergy severity, particularly in allergic responses after fewer exposures to oral allergens.

Limitations & Suggestions

• The differences observed between Tac and Jax mice were assessed only under allergic conditions, while the basal responses of both groups were not shown. Including these baseline controls could help clarify whether the observed differences are attributable to intrinsic responses rather than to the allergic condition itself.

• At present, there are no experiments directly linking the observed changes in Treg cells and allergen-specific T cells to differences in the microbiota. Additional approaches, such as colonizing germ-free Jax mice with specific strains from Tac animals (and vice versa), could help clarify whether the microbiota drives these cellular changes. Alternatively, a more accessible and cost-effective strategy could involve the use of antibiotics to broadly deplete microbiota and assess the resulting effects.

• To further characterize changes in intestinal permeability, it could be informative to measure OVA levels in both serum and small intestine tissue, which would provide a more comprehensive assessment of antigen translocation.

• The study would also benefit from mechanistic experiments aimed at explaining the connection between mast cells and Tregs in the proposed models. Exploring the contribution of each cell type using knockout models could help determine how the in vivo immune response is affected.

•  Finally, it would be interesting to investigate whether specific metabolites produced by the identified bacterial strains are responsible for the observed effects, or to further elucidate how these metabolites may interfere with the underlying biological processes.

Significance/Novelty

While the correlation between food allergy and gut microbiota is well established, the authors provide a novel contribution by examining how reaction severity differs between animals from different vendors, an aspect that has not been extensively explored before. In parallel, previous studies have shown that the microbiota can influence the reactivity threshold in patients, potentially accounting for differences in disease severity among individuals with similar clinical conditions. Building on these observations, the study could be further strengthened by a deeper exploration of the underlying mechanisms, particularly by investigating whether specific metabolites produced by the identified bacterial strains contribute to the observed effects and how they may interfere with the allergic response.

Credit

Reviewed by Elisa Sánchez Martínez as part of a cross-institutional journal club between the Max-Delbrück Center Berlin, the Ragon Institute Boston (Mass General, MIT, Harvard), the University of Virginia, the Medical University of Vienna and other life science institutes in Vienna.

The author declares no conflict of interests in relation to their involvement in the review.