Life-threatening food allergies are constantly increasing in Westernized countries and alterations in the gut microbiome, especially in early life, could contribute to the rise in their prevalence.
Although both a reduced bacterial diversity and an increased Enterobacteriaceae/Bacteroidaceae ratio in infancy have been associated with food sensitization, as well as increased levels of serum immunoglobulin E (IgE) in germ-free and antibiotics-treated mice, how this occurs is still unknown.
A new mouse study, led by researchers in South Korea and Australia, explores the causal mechanisms by which early-life gut microbiota exerts a protective effect against IgE-mediated food allergies.
When young germ-free mice started to eat normal foods just after weaning, they developed an IgE-mediated allergic immune response through CD4+ T cells, with food antigens such as wheat gluten leading to higher IgE levels when compared with ovalbumin.
The new discovery was that the expected increase in the levels of serum IgE occurred together with a spike in interleukin-4-producing T follicular helper (TFH) cells. This subset of cells was generated during the weaning period—and to a lesser extent at adult age—in mesenteric lymph nodes and Peyer’s patches in response to food antigens.
The researchers also found that the presentation of food antigens by dendritic cells and B cells was needed to generate TFH cells in germ-free mice.
In contrast, the mice not exposed to food antigens did not show an increase in IgE accompanied by the impaired generation of TFH cells and CD4+ T cells involved in IgE production in the gut-associated lymphoid tissue.
Finally, they tested the role of commensal microbiota on IgE responses by co-housing the germ-free mice with specific pathogen-free mice and found that this suppressed IgE elevation by dampening the generation of TFH cells. These findings show that the gut microbiota appears to be crucial in protecting mice against food allergy immune responses by keeping TFH cells at bay in the gut-associated lymphoid tissue.
In another recent study, Abdel-Gadir and colleagues found that fecal microbiota from infants and mice with food allergy showed a heightened T helper type 2 cell-like activity against the gut microbiota and against chicken egg ovalbumin-a common food allergy trigger-compared to healthy counterparts.
The transfer of fecal microbiota from infants with a diagnosed food allergy into germ-free mice failed to prevent an anaphylactic response to ovalbumin, whereas the administration of a Clostridiales cluster of human origin alone or together with Subdoligranulum variabilie to mice conferred protection to ovalbumin. The authors also elucidated that the depletion of regulatory T cells that specifically express the transcription factor ROR-gt prevented the protective effects of bacteriotherapy, highlighting its contribution in suppressing food allergy in mice.
Taking into account the emerging role of the gut microbiome in food allergies, scientists have started exploring microbiome-targeted treatments.
For example, a combined therapy comprising the probiotic Lactobacillus rhamnosus CGMCC 1.3724 together with peanut oral immunotherapy was effective in achieving unresponsiveness to a peanut protein in children with an established peanut allergy.
In contrast, the effectiveness of prebiotic supplementation to reduce the risk of food allergies remains uncertain.
Altogether, these findings reinforce the idea that the early-life gut microbiome is worth investigating when attempting to manage food allergies. It appears that the subset of TFH immune cells is a trigger for the development of IgE-mediated food allergies, which were dampened in the presence of gut microbiota following the weaning period.
Hong SW, O E, Lee JY, et al. Food antigens drive spontaneous IgE elevation in the absence of commensal microbiota. Sci Adv. 2019; 5(5):eaaw1507. doi: 10.1126/sciadv.aaw1507.
Abdel-Gadir A, Stephen-Victor E, Gerber GK, et al. Microbiota therapy acts via a regulatory T cell MyD88/RORgt pathway to suppress food allergy. Nat Med. 2019; 25(7):1164-74. doi: 10.1038/s41591-019-0461-z.
Tang ML, Ponsonby AL, Orsini F, et al. Administration of a probiotic with peanut oral immunotherapy: A randomized trial. J Allergy Clin Immunol. 2015; 135(3):737-44. doi: 10.1016/j.jaci.2014.11.034.