Obesity phenotype and gut microbiota alterations are not associated with anxiety-like behaviour in high-fat diet-fed mice.

Anxiety is a common co-morbidity with obesity and metabolic disease, and can lead to a significant impact on quality of life. The vast differences in the gut microbiota between obese and control individuals provide a potential avenue for therapeutic intervention. A high-fat diet (HFD) in rodent models have been shown to induce anxiety-like behaviour and has been tested through an array of distinct behavioural tests such as the elevated plus maze test, light-dark test and open field test. Despite differences in testing and assessment parameters, the behavioural outcomes have previously yielded similar results. Recent evidence suggests that HFD has an anxiolytic effect on mice, complicating the model. Here, we aimed to confirm whether HFD-fed mice are more susceptible to presenting anxiety-like behaviours. Our findings showed no significant differences in behaviour, plasma corticosterone and inflammation markers between HFD and control diet (CTD) mice, despite considerable differences in adiposity and faecal microbial communities. Additionally, daily oral gavage is one of the most common methods for testing bacterial probiotics in rodent models, but this handling could potentially also cause stress to the mice. Thus, we investigated if daily oral gavage could mask differences in HFD and CTD mice. We found no significant differences in weight, fat mass or anxiety-like behaviour in CTD-fed mice with or without daily oral gavage.

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Wong, G., Bearzatto, B., Gala, J.-L., Delzenne, N., Van Hul, M., & Cani, P. (2025). Obesity phenotype and gut microbiota alterations are not associated with anxiety-like behaviour in high-fat diet-fed mice. Food & Function : linking the chemistry and physics of food with health and nutrition, 16(1), 268-281. https://doi.org/10.1039/d4fo04461d (Original work published 2025)