Associations between disordered gut microbiota and changes of neurotransmitters and short-chain fatty acids in depressed mice

Min Wu,Tao Zou,Qiang Mao,Tian Tian,Jing Xie,Jian-Jun Chen,Chan-Juan Zhou

doi:10.1038/s41398-020-01038-3

Abstract

Mounting evidence suggests that gut microbiota can play an important role in pathophysiology of depression, but its specific molecular mechanisms are still unclear. This study was conducted to explore the associations between changes in neurotransmitters and short-chain fatty acids (SCFAs) and altered gut microbiota in depressed mice. Here, the chronic restraint stress (CRS) model of depression was built. The classical behavioral tests were conducted to assess the depressive-like behaviors of mice. The 16S rRNA gene sequence extracted from fecal samples was used to assess the gut microbial composition. Liquid and gas chromatography mass spectroscopy were used to identify neurotransmitters in hypothalamus and SCFAs in fecal samples, respectively. Finally, 29 differential bacteria taxa between depressed mice and control mice were identified, and the most differentially abundant bacteria taxa were genus Allobaculum and family Ruminococcaceae between the two groups. The acetic acid, propionic acid, pentanoic acid, norepinephrine, 5-HIAA and 5-HT were significantly decreased in depressed mice compared to control mice. Genus Allobaculum was found to be significantly positively correlated with acetic acid and 5-HT. Taken together, these results provided novel microbial and metabolic frameworks for understanding the role of microbiota-gut-brain axis in depression, and suggested new insights to pave the way for novel therapeutic methods.

Highlights

Depression is a debilitating disease that involves a loss of interest in activities, a low mood and a persistent feeling of sadness
Previous studies have been reported that chronic stress could result in the disturbance of gut microbiota and host metabolism, which might contribute to the development of depression[26,27]
We found that the gut microbiota, short-chain fatty acids (SCFAs) in fecal sample and neurotransmitters in hypothalamus were significantly changed in depressed mice compared to control mice

Summary

Introduction

Depression is a debilitating disease that involves a loss of interest in activities, a low mood and a persistent feeling of sadness. Depression has become the leading cause of disability globally and affects nearly 6% of the adult population worldwide each year[1]. It is the result of complex gene-environment interactions. The genetic contribution to this disease is expected to be nearly 35%, and environmental factors (such as sexual and stress) are strongly related with the development of depression[2,3]. Many theories have been developed to explain the pathogenesis of depression, such neurotransmission deficiency and endocrine-immune system dysfunction[4,5]. None of these theories has been universally accepted. It is urgently needed to find a novel pathophysiologic mechanisms underlying depression

Methods

Results

Conclusion