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Whether dietary salt contributes to asthma incidence, remains controversial. We aimed to investigate the impact of higher salt intake on asthma incidence in humans and to evaluate underlying mechanisms using mouse models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Epidemiological research was conducted using the UK Biobank Resource. Data were obtained from 42,976 participants with a history of allergies. 24\u2010h sodium excretion was estimated from spot urine, and its association with asthma incidence was assessed by Cox regression, adjusting for relevant covariates. For mechanistic studies, a mouse model of mite\u2010induced allergic airway inflammation (AAI) fed with high\u2010salt diet (HSD) or normal\u2010salt chow was used to characterize disease development. The microbiome of lung and feces (as proxy for gut) was analyzed via 16S rRNA gene based metabarcoding approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In humans, urinary sodium excretion was directly associated with asthma incidence among females but not among males. HSD\u2010fed female mice displayed an aggravated AAI characterized by increased levels of total IgE, a T<jats:sub>H<\/jats:sub>2\u2010T<jats:sub>H<\/jats:sub>17\u2010biased inflammatory cell infiltration accompanied by upregulation of osmosensitive stress genes. HSD induced distinct changes in serum short chain fatty acids and in both gut and lung microbiome, with a lower <jats:italic>Bacteroidetes<\/jats:italic> to <jats:italic>Firmicutes<\/jats:italic> ratio and decreased <jats:italic>Lactobacillus<\/jats:italic> relative abundance in the gut, and enriched members of <jats:italic>Gammaproteobacteria<\/jats:italic> in the lung.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>High dietary salt consumption correlates with asthma incidence in female adults with a history of allergies. Female mice revealed HSD\u2010induced T\u2010cell lung profiles accompanied by alterations of gut and lung microbiome.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16148","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T05:36:00Z","timestamp":1716788160000},"page":"1844-1857","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The impact of high\u2010salt diet on asthma in humans and mice: Effect on specific T\u2010cell signatures and microbiome"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8356-4343","authenticated-orcid":false,"given":"Stephanie","family":"Musiol","sequence":"first","affiliation":[{"name":"Center of Allergy &amp; Environment (ZAUM) Technical University of Munich (TUM) and Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health  Neuherberg Germany"},{"name":"Member of the German Center of Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9003-6976","authenticated-orcid":false,"given":"Carla P.","family":"Harris","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health  Neuherberg Germany"},{"name":"Dr. von Hauner Children's Hospital, University Hospital LMU of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6379-3728","authenticated-orcid":false,"given":"Silvia","family":"Gschwendtner","sequence":"additional","affiliation":[{"name":"Research Unit for Comparative Microbiome Analysis Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5326-5603","authenticated-orcid":false,"given":"Amy","family":"Burrell","sequence":"additional","affiliation":[{"name":"Department of Infection Immunology, Leibniz Institute for Natural Product Research &amp; 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