Written by Joyce Smith, BS. This study suggests new diagnostic biomarkers for the identification of major depressive disorder (MDD).
MDD is a common and debilitating mental disorder 1,2 that is difficult to diagnose. Because of a lack of biomarkers and an understanding of the underlying pathophysiological mechanisms 3, MDD diagnosis has relied singularly on clinical interviews, resulting in substantial misdiagnosis 4. Although several hypotheses have attempted to explain its pathophysiological mechanisms, the underlying molecular basis of MDD remains obscure 3. Thus, it is critical to advance research and develop reliable diagnostic biomarkers for MDD.
The human gut microbiome is a community of bacteria, viruses, fungi, and protozoa living symbiotically within the gastrointestinal tract. Little is known about the role of these viruses, bacteria, and fecal metabolome, and how they interact in MDD. A current study by Yang and colleagues 5 identifies a microbiome that is associated with MDD, as well as provides a profile of molecules these organisms produce. For this study, researchers collected fecal samples (n=311) from 236 people; half of them had been diagnosed with MDD and were medication free, the other half were healthy controls (HCs). Using a cross-sectional whole-genome shotgun metagenomics analysis, they sequenced the total genomic DNA of all the bacteria and viruses in the fecal samples and, with statistical programs, were able to characterize the signatures of gut bacteriophages and bacteria as well as their functional potential. This microbial “fingerprint” was used to distinguish between individuals with MDD and healthy controls, based on the composition of microbes and compounds in their fecal material.
Analyses found significant differences between the microbiomes of the MDD and HC groups. Eighteen bacterial species, predominantly of the genus Bacteroides, were more abundant in people with MDD compared to healthy controls. Less common were 29 species primarily of the genera Blauti and Eubacterium. Also evident were the presence of three bacteriophages (viruses that infect bacteria) whose levels were different in the MDD group compared to the healthy controls. The metabolic profile of the organisms differed as well. Gas chromatography-mass spectrometry (GC-MS) of the entire gut microbiome revealed that that MDD patients harbored significantly more of 16 metabolites and less of 34 compounds than did healthy controls. Most of these altered microbial genes and fecal metabolites were involved in amino acid metabolism of which the three most important were amino gamma-aminobutyric acid (GABA), phenylalanine, and tryptophan metabolisms.
Lastly a biomarker panel consisting of two species of bacteria, two types of bacteriophage viruses, and two different metabolites was created that could discriminate around 90 % of the time between MMD patients and HCs in a subset of 75 participants, half with MDD and half were HCs.
The brain neurotransmitter GABA is also produced by bacteria. Researchers found decreased fecal levels of GABA and certain of its metabolites in the MDD patients, as well as altered GABA-related microbial genes, suggesting that microbes can modulate brain GABA levels which lead to depressive symptoms. In line with these assumptions are previous studies that demonstrated how microbial-derived GABA influenced the host through the gut-brain axis 6, how GABA-producing microbes improved depression-like behavior 7 and thirdly, that a decrease in gut GABA level correlated with the dysregulation of GABAergic function in the brain 8. When the microbiome increases in Bacteroides bacteria, cytokine production occurs and inflammation increases, while Blautia bacteria, known for its anti-inflammatory activity, decreases; thus, both species contribute to MDD.
These findings suggest that fecal GABA level in patients with MDD is modulated by a panel of gut microbes, which are implicated in the development of MDD. However, animal studies are needed to further clarify how an altered gut microbiome leads to the development of MDD.
Source: Yang, Jian, Peng Zheng, Yifan Li, Jing Wu, Xunmin Tan, Jingjing Zhou, Zuoli Sun et al. “Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders.” Science advances 6, no. 49 (2020): eaba8555.
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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Posted December 21, 2020.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
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- Yang J, Zheng P, Li Y, et al. Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders. Sci Adv. 2020;6(49).
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- Patterson E, Ryan PM, Wiley N, et al. Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome. Sci Rep. 2019;9(1):16323.
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