Functional iron-deficiency in allergics correlate with symptom severity and microbial communities not relying on iron

Background: Epidemiological studies suggest that allergy is associated with iron deficiency. We compared iron and microbial parameters of allergic and non-allergic women without anemia and associated them with the clinical response of allergic rhinitis subjects during nasal provocation.Methods: Dietary habits of female subjects donating blood, stool and urine samples were assessed. A second cohort of women with allergic rhinitis donated only stool and blood and underwent a graded nasal provocation against pollen extract., before clinical reactivity parameters were recorded. Complete blood cell count and iron metabolism markers were determined. Stool samples were subjected to 16S rRNA gene amplicon sequencing. Trace element concentrations in serum and aqueous stool extracts were determined via inductively coupled plasma-sector field mass spectrometry (ICP-SFMS).Results: Dietary iron intake did not differ in allergics compared to non-allergics, though allergics had significantly lower metabolic active iron in their circulation and excreted significantly more urinary hepcidin. Nasal and serum ceruloplasmin was the sole protein marker that correlated with all assessed symptom parameters. A positive correlation to symptoms was confirmed with ceruloplasmin, whereas gut iron and gut cobalt showed an inverse relationship to clinical symptoms. The members of the genera Bacteroides and Ruminococcus were associated with lower TNSS symptoms, with significantly lower levels present in allergic compared to non-allergic subjects.Conclusion: The study shows for the first time that even in non-anemic allergic patients, functional iron-parameters are linked with increased hepcidin production contributing to the lower iron availability in allergics. The copper-containing ferroxidase ceruloplasmin correlated with the allergic outcome, whereas gut iron and bacterial members of the genera Bacteriodes and Ruminococcus were associated with decreased immune reactivity in adult hay fever.Sequencing was performed at the Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna under the project ID JMF-1902-6.