The prevalence of food allergies continues to rise, and with limited existing therapeutic options there is a growing need for new and innovative treatments. Food allergies are, in a large part, related to environmental influences on immune tolerance in early life, and represent a significant therapeutic challenge. An expanding body of evidence on molecular mechanisms in murine models and microbiome associations in humans have highlighted the critical role of gut dysbiosis in the pathogenesis of food allergies. As such, the gut microbiome is a rational target for novel strategies aimed at preventing and treating food allergies, and new methods of modifying the gastrointestinal microbiome to combat immune dysregulation represent promising avenues for translation to future clinical practice. In this review, we discuss the intersection between the gut microbiome and the development of food allergies, with particular focus on microbiome therapeutic strategies. These emerging microbiome approaches to food allergies are subject to continued investigation and include dietary interventions, pre- and probiotics, microbiota metabolism-based interventions, and targeted live biotherapeutics. This exciting frontier may reveal disease-modifying food allergy treatments, and deserves careful study through ongoing clinical trials.

Background

Inadequate titers of pneumococcal antibody (PA) are commonly present among patients with recurrent respiratory infections.

Objective

We sought to determine the effect of the degree of inadequacy in baseline PA titers on the subsequent polysaccharide vaccine response, the incidence of sinusitis, and allergic conditions.

Methods

A total of 313 patients aged 6 to 70 years with symptoms of recurrent respiratory infections were classified by baseline-pPA (percentage of protective [≥1.3 µg/mL] PA serotypes/total tested serotypes) and postvaccination pPA (post-pPA): Group A (adequate baseline-pPA), Group B (inadequate baseline-pPA, adequate post-pPA, responders), and Group C (inadequate baseline-pPA, inadequate postpPA, nonresponders, specific antibody deficiency [SAD]). Immunity against Streptococcus pneumoniae was defined as adequate when the pPA was ≥70%. Each group and combined groups, Group AB (inadequate baseline-pPA), and Group BC (adequate post-pPA) were analyzed for demographics, history of sinusitis, recurrent sinusitis in the following year, allergic conditions, and association with inadequate individual serotype titers.

Results

Over 80% of patients with respiratory symptoms had inadequate baseline-pPA. Baseline-pPA and SAD prevalence are inversely related (odds ratio = 2.02, 95% CI: 1.15-3.57, P = .01). Inadequate serotype 3 antibody titer is highly associated with SAD (odds ratio = 2.02, 96% CI: 1.61-5.45, P < .01). The groups with inadequate pPA (Group B and C, or BC) had significantly higher percentage of patients with chronic rhinosinusitis (P < .001), allergic sensitization, and allergic rhinitis (P < .05). Group A contained higher percentage of patients with recurrent upper airway infections (P < .001).

Conclusion

Low baseline-pPA and low antibody titers to serotype 3 are highly associated with SAD, increased incidence of respiratory infections including CRS and allergic conditions.

BACKGROUND: The pathogenesis of Crohns disease involves genetic and environmental factors, with the gut microbiome playing a crucial role. The Crohns disease-associated variant rs13107325 in the SLC39A8 gene results in an A391T substitution in the ZIP8 metal ion transporter and has previously been linked to alterations in the colonic microbiome in variant carriers. We hypothesized that the A391T substitution alters metal ion homeostasis in the colonic mucosal-luminal interface, thereby inducing dysbiosis which may promote intestinal inflammation. METHODS: To evaluate this hypothesis, we generated a SLC39A8 A393T mouse model (matching human A391T). We first examined trace element abundance in the colonic mucosal epithelium and lumen of homozygous A393T and wild-type (WT) mice to determine if the variant affected metal distribution. We also performed 16S rRNA gene sequencing on colon samples at 2 months, 3-4 months, and 12 months of age, and conducted histological scoring of colon tissue collected from 5-month and 10-month old mice. RESULTS: Consistent with an effect of the variant on ZIP8 function, homozygous A393T mice exhibited increased cobalt in the colonic mucosa, but reduced iron, zinc, manganese, cobalt, copper, and cadmium in the colonic lumen. 16S rRNA gene sequencing of colon samples revealed variant-linked effects on microbiome beta diversity in 2-month-, 3-4-month-, and 12-month-old mice. Histological scoring showed spontaneous intestinal inflammation in 10-month but not in 5-month-old mice. Lastly, predicted pathway analysis of the microbiome samples revealed differential enrichment of iron-, zinc-, and cobalt-dependent pathways in A393T mice compared to wild-type controls. CONCLUSION: These results suggest that the variant in SLC39A8 primarily restricts metal availability to the microbiota, resulting in compositions that can adapt to the environment and that A393T-linked dysbiosis occurs prior to the onset of inflammation. This study paves the way for future studies investigating risk variants as microbiome-disease modifiers.