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Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in major depressive disorder patients

Published online by Cambridge University Press:  05 November 2019

Wen-tao Lai ,
Wen-feng Deng ,
Shu-xian Xu ,
Jie Zhao ,
Dan Xu ,
Yang-hui Liu ,
Yuan-yuan Guo ,
Ming-bang Wang ,
Fu-sheng He  and
Shu-wei Ye
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Wen-tao Lai
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Wen-feng Deng
Affiliation:
Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
Shu-xian Xu
Affiliation:
Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
Jie Zhao
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Dan Xu
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Yang-hui Liu
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Yuan-yuan Guo
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Ming-bang Wang
Affiliation:
Xiamen Branch, Shanghai Key Laboratory of Birth Defects, Division of Neonatology, Children's Hospital of Fudan University, National Center for Children's Health, Shanghai, China
Fu-sheng He
Affiliation:
Imunobio, Shenzhen, Guangdong, China
Shu-wei Ye
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Qi-fan Yang
Affiliation:
Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
Tie-bang Liu
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Ying-li Zhang
Affiliation:
Department of Depression, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Sheng Wang
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Min-zhi Li
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Ying-jia Yang
Affiliation:
Department of Depression, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Xin-hui Xie*
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China Center of Acute Psychiatry Service, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
Han Rong
Affiliation:
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China Affiliated Shenzhen Clinical College of Psychiatry, Jining Medical University, Jining, Shandong, China
*
Authors for correspondence: Xin-hui Xie, E-mail: xxh.med@gmail.com; Han Rong, E-mail: Ronghansz@126.com
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Abstract

Background

The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.

Methods

We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.

Results

The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.

Conclusions

The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.

Keywords

Gastrointestinal microbiomemajor depression disorderRandom Forest algorithmserotoninshotgun metagenomics sequencingtryptophan
Type
Original Articles
Information
Psychological Medicine , Volume 51 , Issue 1 , January 2021 , pp. 90 - 101
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Copyright
Copyright © Cambridge University Press 2019

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Footnotes

†

The first three authors, Wen-tao Lai, Wen-feng Deng, and Shu-xian Xu contributed equally to this paper.

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