Metabolome and microbiome profiling of a stress-sensitive rat model of gut-brain axis dysfunction

Shalome A Bassett,Karl Fraser,Julie E Dalziel,John F Cryan,Leigh Ryan,Niall Hyland,Patrick Fitzgerald,Jim Webster,Timothy G Dinan,Wayne Young,Gerard Clarke,Nicole C Roy,Catherine Stanton

doi:10.1038/s41598-019-50593-3

Abstract

Stress negatively impacts gut and brain health. Individual differences in response to stress have been linked to genetic and environmental factors and more recently, a role for the gut microbiota in the regulation of stress-related changes has been demonstrated. However, the mechanisms by which these factors influence each other are poorly understood, and there are currently no established robust biomarkers of stress susceptibility. To determine the metabolic and microbial signatures underpinning physiological stress responses, we compared stress-sensitive Wistar Kyoto (WKY) rats to the normo-anxious Sprague Dawley (SD) strain. Here we report that acute stress-induced strain-specific changes in brain lipid metabolites were a prominent feature in WKY rats. The relative abundance of Lactococcus correlated with the relative proportions of many brain lipids. In contrast, plasma lipids were significantly elevated in response to stress in SD rats, but not in WKY rats. Supporting these findings, we found that the greatest difference between the SD and WKY microbiomes were the predicted relative abundance of microbial genes involved in lipid and energy metabolism. Our results provide potential insights for developing novel biomarkers of stress vulnerability, some of which appear genotype specific.

Highlights

Stress negatively impacts gut and brain health
The Forced swim test (FST)-induced stress response was used to verify that the Wistar Kyoto (WKY) rats displayed an acute stress hypothalamic pituitary adrenal axis (HPA) response and accompanying behaviour profile and physiology
A key finding from our study has been the identification of differential physiological responses to acute stress, with respect to lipid metabolism, where Sprague Dawley (SD) rats had increased levels of plasma lipids while WKY rats had altered brain lipid profiles

Summary

Introduction

Stress negatively impacts gut and brain health. Individual differences in response to stress have been linked to genetic and environmental factors and more recently, a role for the gut microbiota in the regulation of stress-related changes has been demonstrated. The microbiome-gut-brain axis is influenced by stress while the gut microbiota plays a significant role in regulating stress-related responses[1]. Given the significant comorbidity of stress-related disorders and gut disorders, animal models of stress and anxiety are routinely used to study functional gastrointestinal disorders such as irritable bowel syndrome (IBS)[2–5] as well as to develop new, more efficient pharmacological and/or behavioural treatments[2,6–8]. These models have been applied to study the effects of diet and food components on stress[9–11]. The Wistar Kyoto (WKY) rat strain is a model commonly used to study stress, anxiety and depression, as well as visceral hypersensitivity[22,23] general. Analysis mode Polar positive Polar negative Lipid positive Lipid negative studying gut-brain axis (GBA) dysfunction[25] because susceptibility to chronic stress often results in anxiety and gut microbiota alterations[26]

Methods

Results

Discussion

Conclusion