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

  • Wen-tao Lai (a1), Wen-feng Deng (a2), Shu-xian Xu (a2), Jie Zhao (a1), Dan Xu (a1), Yang-hui Liu (a1), Yuan-yuan Guo (a1), Ming-bang Wang (a3), Fu-sheng He (a4), Shu-wei Ye (a1), Qi-fan Yang (a2), Tie-bang Liu (a1), Ying-li Zhang (a5), Sheng Wang (a1), Min-zhi Li (a1), Ying-jia Yang (a5), Xin-hui Xie (a1) (a2) (a6) and Han Rong (a1) (a7)...



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.


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.


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.


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.


Corresponding author

Authors for correspondence: Xin-hui Xie, E-mail:; Han Rong, E-mail:


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



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

  • Wen-tao Lai (a1), Wen-feng Deng (a2), Shu-xian Xu (a2), Jie Zhao (a1), Dan Xu (a1), Yang-hui Liu (a1), Yuan-yuan Guo (a1), Ming-bang Wang (a3), Fu-sheng He (a4), Shu-wei Ye (a1), Qi-fan Yang (a2), Tie-bang Liu (a1), Ying-li Zhang (a5), Sheng Wang (a1), Min-zhi Li (a1), Ying-jia Yang (a5), Xin-hui Xie (a1) (a2) (a6) and Han Rong (a1) (a7)...


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