Consumption of dietary emulsifiers increases sensitivity to social stress in mice: A potential role for the COX molecular pathway
Year: 2025
Type: article
Abstract: BACKGROUND: Chronic low-grade inflammation and exposure to stress are key contributing factors in the etiology and progression of many neuropsychiatric disorders. Dietary emulsifiers, such as carboxymethylcellulose (CMC) and polysorbate-80 (P80), are commonly added to processed foods and drinks and are classified by the Food and Drug Administration (FDA) as generally recognized as safe (GRAS). Recently, however, we and others have reported that these additives at translationally relevant doses cause low-grade intestinal inflammation, microbiota dysbiosis, and alterations in gene expression in brain areas that mediate behavioral and neuroendocrine responses to stress-provoking stimuli. METHODS: To test whether emulsifier exposure sensitizes behavioral, hormonal, and neuronal responses to stress, C57BL/6 J male mice were given water +1 % emulsifier (CMC or P80) or water alone for 12 weeks after which they were exposed to social defeat stress. We previously found increased PTGS2 (COX-2) gene expression in the amygdala following emulsifier consumption. To determine whether inflammation, potentially through the COX pathway, is a potential mechanism driving emulsifier-induced increases in stress sensitivity, we administered the COX inhibitor aspirin (25 mg/kg/day) in conjunction with emulsifiers for the last six weeks of treatment. RESULTS: In defeated mice, CMC increased circulating corticosterone, while both emulsifiers increased social avoidance behavior and altered defeat-induced c-Fos immunofluorescence in various brain regions. Moreover, behavioral and hormonal alterations were attenuated by aspirin. CONCLUSIONS: These data demonstrate that ingestion of at least some dietary emulsifiers at concentrations analogous to those ingested by humans increases sensitivity to social stress in mice and that the COX pathway may be a mechanistic candidate by which emulsifier-induced increases in sensitivity to social stress occur.
Source: Hormones and Behavior
Authors: Amanda R. Arnold, Benoit Chassaing, Kiran Lakhani, Coralie Bergeron, Emma K. Shaughnessy, Anna M. Rosenhauer, Maura C. Stoehr, Benjamin Horne, Tyler Wilkinson, Kim L. Huhman
Language: English
Subfield: Behavioral Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,640
Funders: Georgia Southern University, Fondation de l'Avenir pour la Recherche Médicale Appliquée, Georgia State University, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, National Institutes of Health, Horizon 2020 Framework Programme, European Research Council, Horizon 2020, National Institute of Mental Health, Vermont Agency of Natural Resources
Awards: EMULBIONT: Impact of dietary food additive EMULsifiers on pathoBIONT’s pathogenic potential in chronic inflammatory diseases: from mechanism to prevention, G1309800035, G1554833418, G2522628222, G3186420570, Dynamique de la REsistance aux Antibiotiques dans le Microbiote intestinal humain: combinaison d'une cohorte informée sur nutrition à des études quantitatives sur un modèle in vitro d'intestin, G4180218856, G6639905357, G8423049057, G8934596923, Sex-dependent regulation of social reward by oxytocin in the mesolimbic reward circuitry
OpenAlex ID: W4409961858