Consumption of dietary emulsifiers increases sensitivity to social stress in mice: A potential role for the COX molecular pathway

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.