# OVA-Induced Food Allergy Leads to Neurobehavioral Changes in Mice and the Potential Role of Gut Microbiota and Metabolites Dysbiosis

## TL;DR

OVA-induced food allergy in mice causes neurobehavioral issues like anxiety and depression, possibly linked to gut microbiota and amino acid metabolism changes.

## Contribution

This study reveals a potential role of gut microbiota and metabolite dysbiosis in neurobehavioral changes caused by food allergy in mice.

## Key findings

- OVA mice showed elevated IgE and Th2 cytokines, along with anaphylactic symptoms.
- OVA mice exhibited anxiety, depression, repetitive behaviors, and impaired social interaction and attention.
- Gut microbiota dysbiosis and amino acid metabolism disruption correlated with neuroinflammation and behavioral abnormalities.

## Abstract

The neurobehavioral changes in food allergy mice have not been comprehensively studied, and the mechanism underlying them remains unclear. Our study aims to fully investigate neurobehavioral changes in OVA (ovalbumin)-sensitized food allergy mice and explore the potential mechanism via the gut microbiota–brain 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-α, IL-1β, 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.