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Research
Changes in Gut Viral and Bacterial Species Correlate with Altered 1,2-Diacylglyceride Levels and Structure in the Prefrontal Cortex in a Non-Human Primate Model of Depression.
Peng Xie
Chongqing Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5319-7842
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Major depressive disorder (MDD) is a debilitating mental disease, but its underlying molecular mechanisms remain obscure. Gut microbiome can modulate brain function and behaviors through the microbiota-gut–brain (MGB) axis in depression. Our previously established non-human primate model of naturally occurring depression-like behaviors, which is characterized by MGB axis disturbances, can be used to interrogate how a disturbed gut ecosystem may modulate the MDD onset. To better clarify the molecular interrelationships and downstream functional consequences in the MGB axis on MDD pathology, here, gut metagenomics were used to characterize how gut virus and bacterial species, and associated metabolites, change in depressive monkey model.
Results: We identified a panel of 33 gut virus and 14 bacterial species that could discriminate the depression-like (DL) from control M. fascicularis. In addition, using lipidomic analyses of central and peripheral samples obtained from these animals, we found that the DL macaque were characterized by alterations in the relative abundance, carbon-chain length, and unsaturation degree of 1,2-diacylglyceride (DG) in the prefrontal cortex (PFC), in a brain region-specific manner. In addition, lipid-reaction analysis identified more active and inactive lipid pathways in PFC than in amygdala or hippocampus, with DG being a key nodal player in these lipid pathways. Significantly, co-occurrence network analysis showed that altered gut viral and bacterial species, and their interaction may be relevant to the onset of negative emotions behaviors by modulating the DG levels in PFC in the depressive macaque.
Conclusions: Our findings suggest that altered gut virus and bacteria as well as DG levels and structure in the PFC are hallmarks of the DL macaque, thus providing a new framework for understanding the gut microbiome's role in depression.
Keywords
major depressive disorder, Macaca fascicularis, gut microbiome, lipidomics, metagenomics
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Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and accessed as a PDF.
This is a list of supplementary files associated with this preprint. Click to download.
- Additionfile1.docx
Addition file 1: Figure S1. Discriminating lipids in brain regions and plasma between HC and DL groups.
- Additionfile2.docx
Addition file 2: Figure S2. Pathway activity of lipid showed changed reactions among brain regions in DL group relative to HC group.
- Additionfile3.docx
Addition file 3: Table S1. Discriminatory gut virus between DL and HC groups.
- Additionfile4.docx
Addition file 3: Table S2. Discriminatory bacterial species between DL and HC groups.
- workflow.pdf
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Research
Changes in Gut Viral and Bacterial Species Correlate with Altered 1,2-Diacylglyceride Levels and Structure in the Prefrontal Cortex in a Non-Human Primate Model of Depression.
Peng Xie
Chongqing Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5319-7842
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 31 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
General Microbiology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Major depressive disorder (MDD) is a debilitating mental disease, but its underlying molecular mechanisms remain obscure. Gut microbiome can modulate brain function and behaviors through the microbiota-gut–brain (MGB) axis in depression. Our previously established non-human primate model of naturally occurring depression-like behaviors, which is characterized by MGB axis disturbances, can be used to interrogate how a disturbed gut ecosystem may modulate the MDD onset. To better clarify the molecular interrelationships and downstream functional consequences in the MGB axis on MDD pathology, here, gut metagenomics were used to characterize how gut virus and bacterial species, and associated metabolites, change in depressive monkey model.
Results: We identified a panel of 33 gut virus and 14 bacterial species that could discriminate the depression-like (DL) from control M. fascicularis. In addition, using lipidomic analyses of central and peripheral samples obtained from these animals, we found that the DL macaque were characterized by alterations in the relative abundance, carbon-chain length, and unsaturation degree of 1,2-diacylglyceride (DG) in the prefrontal cortex (PFC), in a brain region-specific manner. In addition, lipid-reaction analysis identified more active and inactive lipid pathways in PFC than in amygdala or hippocampus, with DG being a key nodal player in these lipid pathways. Significantly, co-occurrence network analysis showed that altered gut viral and bacterial species, and their interaction may be relevant to the onset of negative emotions behaviors by modulating the DG levels in PFC in the depressive macaque.
Conclusions: Our findings suggest that altered gut virus and bacteria as well as DG levels and structure in the PFC are hallmarks of the DL macaque, thus providing a new framework for understanding the gut microbiome's role in depression.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and accessed as a PDF.