Western diet-induced anxiolytic effects in mice are associated with alterations in tryptophan metabolism.

ABSTRACT

OBJECTIVES: Western-style diets high in saturated fat and refined carbohydrate have been shown to alter gut microbiota as well as being associated with altered behaviour and learning ability. The objective of this study was to determine the effects of short-term intake of a Western-style diet on intestinal cytokine expression, tryptophan metabolism, and levels of neurotransmitters in the brain. METHODS: At 7 weeks of age, 129S1/SvImJ mice were placed on a standard chow or Western-style diet (fat 33%, refined carbohydrates 49%) for 3 weeks. Anxiety-like behaviour was assessed by the latency to step-down test and exploration assessed in a Barnes maze. Neurotransmitter levels in forebrains were analysed by high-pressure liquid chromatography. Liver metabolism was examined by 1H nuclear magnetic resonance (NMR). Cytokine expression in the intestine was measured using MesoScale discovery platform. mRNA levels of tryptophan hydroxylase (Tph) and indoleamine 2,3-dioxygenase (IDO) in the brain and intestine were measured using qPCR. RESULTS: Results showed that mice fed the Western diet displayed reduced exploratory and anxiety-like behaviour. Anxiolytic effects correlated with increased hippocampal brain-derived neurotrophic factor (BDNF) and tryptophan levels. Brain serotonin was not altered. These changes were associated with reduced expression of small intestinal indoleamine 2,3-dioxygenase, a tryptophan-processing enzyme. Western diet-fed mice exhibited low-grade systemic and intestinal inflammation along with altered liver metabolic profiles. DISCUSSION: In conclusion, diets high in fat and refined sugar are associated with increased levels of brain BDNF and tryptophan and decreased exploratory and anxiety-like behaviour. These behavioural changes correlated with altered intestinal tryptophan metabolism and liver metabolic profiles.