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Our study aims to fully investigate neurobehavioral changes in OVA (ovalbumin)-sensitized food allergy mice and explore the potential mechanism via the gut microbiota\u2013brain axis. We established the food allergy mouse (C57BL\/6J male) model with OVA, evaluating the anaphylactic symptoms and the levels of Th2 signature cytokine and allergy-related antibodies in serum. Using behavioral tests, we measured anxiety, depression, social behavior, repetitive behavior, attention, and spatial memory in control and OVA mice. In addition, we analyzed the prefrontal cortex for measuring inflammation-related indicators and gathered serum for untargeted metabolomics analysis and feces for 16S rDNA sequencing. OVA mice exhibited anaphylactic symptoms and significantly elevated serum IgE and Th2 signature cytokine levels. In addition to anxiety-like, depression-like, and repetitive behaviors, OVA mice also displayed less social interest and damaged attention. TNF-\u03b1, IL-1\u03b2, and IL-6 levels and the activation of microglia in the prefrontal cortex of OVA mice were significantly increased, which might explain the neuronal damage. Using multi-omics technology, amino acid metabolism disruption, particularly carboxylic acids and derivatives, was observed in OVA mice, which was remarkably correlated with the altered abundance of gut microbiota related to food allergy. Behaviors in OVA-induced food allergy mice were extensively impaired. The disruption of amino acid metabolism associated with gut microbiota dysbiosis in OVA mice might play a pivotal role in impairing neural immune homeostasis and neuronal damage, which could be responsible for behavioral abnormalities.<\/jats:p>","DOI":"10.3390\/ijms26104760","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T05:11:57Z","timestamp":1747372317000},"page":"4760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["OVA-Induced Food Allergy Leads to Neurobehavioral Changes in Mice and the Potential Role of Gut Microbiota and Metabolites Dysbiosis"],"prefix":"10.3390","volume":"26","author":[{"given":"Shouxun","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Developmental and Behavioral Pediatrics, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Translational Medicine Institute, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Developmental and Behavioral Pediatrics, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luanluan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Developmental and Behavioral Pediatrics, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Developmental and Behavioral Pediatrics, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"},{"name":"State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.jaci.2010.10.008","article-title":"Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report","volume":"126","author":"Boyce","year":"2010","journal-title":"J. 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