Dietary emulsifiers consumption alters anxiety-like and social-related behaviors in mice in a sex-dependent manner

Mary K Holder,Christopher T Fields,Nicole V Peters,Andrew T Gewirtz,Geert J De Vries,Jack Whylings,Benoit Chassaing

doi:10.1038/s41598-018-36890-3

Mary K Holder, Christopher T Fields + Show 5 more

Open Access

https://doi.org/10.1038/s41598-018-36890-3

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Abstract

Dietary emulsifiers carboxylmethylcellulose (CMC) and polysorbate 80 (P80) alter the composition of the intestinal microbiota and induce chronic low-grade inflammation, ultimately leading to metabolic dysregulations in mice. As both gut microbiota and intestinal health can influence social and anxiety-like behaviors, we investigated whether emulsifier consumption would detrimentally influence behavior. We confirmed that emulsifier exposure induced chronic intestinal inflammation, increased adiposity, and altered gut microbiota composition in both male and female mice, although the specific microboal taxa altered following emulsifier consumption occurred in a sex-dependent manner. Importantly, emulsifier treatment altered anxiety-like behaviors in males and reduced social behavior in females. It also changed expression of neuropeptides implicated in the modulation of feeding as well as social and anxiety-related behaviors. Multivariate analyses revealed that CMC and P80 produced distinct clustering of physiological, neural, and behavioral effects in male and female mice, suggesting that emulsifier treatment leads to a syndrome of sex-dependent changes in microbiota, physiology, and behavior. This study reveals that these commonly used food additives may potentially negatively impact anxiety-related and social behaviors and may do so via different mechanisms in males and females.

Highlights

The notion that the viscera or gut influences our emotions dates back over 100 years[1], and recent studies suggest this influence may be related to pathology
In accord with our previous work[26], twelve weeks of exposure to emulsifiers carboxymethylcellulose (CMC) or polysorbate (P80) via drinking water led to a marked increase in abdominal adiposity that was associated with chronic mild intestinal inflammation, as revealed by shorter colons and increased spleen weight (Fig. 1 and Supplemental Fig. 1)
Using Principal Coordinate Analysis (PCoA) of the unweighted UniFrac distances, we first examined the differences in microbiota composition before treatments begin (P21)

Summary

Introduction

The notion that the viscera or gut influences our emotions dates back over 100 years[1], and recent studies suggest this influence may be related to pathology. Germ-free animals are protected from intestinal inflammation and metabolic abnormalities following emulsifier exposure, and transplant of microbiota from emulsifier-treated animals to germ-free recipient mice is sufficient to confer metabolic alterations, indicating that microbiota drive this phenotype[26]. We found that emulsifier treatment altered anxiety-like and social behaviors, and did so in a sex-specific manner Such sex-specific differences were paralleled by emulsifiers differentially impacting microbiota composition, inflammation, and metabolism. These results demonstrate the potential for food additives that alter the intestinal environment to broadly influence physiology and behavior

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