Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders

Yang, Jian; Zheng, Peng; Li, Yifan; Wu, Jing; Tan, Xunmin; Zhou, Jingjing; Sun, Zuoli; Chen, Xu; Zhang, Guofu; Zhang, Hanping; Huang, Yu; Chai, Tingjia; Duan, Jiajia; Liang, Weiwei; Yin, Bangmin; Lai, Jianbo; Huang, Tingting; Du, Yanli; Zhang, Peifen; Jiang, Jiajun; Xi, Caixi; Wu, Lingling; Lu, Joan; Mou, Tingting; Xu, Yi; Perry, Seth W.; Wong, Ma‐Li; Licinio, Júlio; Hu, Shaohua; Wang, Gang

doi:10.1126/sciadv.aba8555

Cited by 244 publications

(201 citation statements)

References 42 publications

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“…In the DL macaques, the altered phages mainly parasitize Proteobacteria and Firmicutes bacteria. Interestingly, we recently found similar viral disturbances in MDD patients [36], in which the altered gut viruses were mainly bacteriophages too. The MDD patients had increased Siphoviridae but decreased Podoviridae viral family populations, which aligns with our findings in the DL macaques described herein.…”

Section: Discussionmentioning

confidence: 54%

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.

Wu¹,

Chai²,

Zhang³

et al. 2020

Preprint

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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.

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Section: Discussionmentioning

confidence: 54%

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.

Wu¹,

Chai²,

Zhang³

et al. 2020

Preprint

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“…Bacteroidales is the most common microbial category in the human gut. It takes signi cant roles in metabolic pathways and immune system (47). Previous studies reported that acquired inter bacterial defense gene clusters in Bacteroidales species reside in the human gut microbiome.…”

Section: Discussionmentioning

confidence: 99%

Assessing the Effect of Interaction Between C-Reactive Protein and Gut Microbiome on the Risks of Anxiety and Depression

Chen

Meng

Cheng

et al. 2021

Preprint

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Cumulative evidence shows that gut microbiome can influence brain function and behavior via the inflammatory processes. However, the role of interaction between gut dysbiosis and C-reactive protein (CRP) in the development of anxiety and depression remains to be elucidated. In this study, a total of 3,321 independent SNP loci associated with gut microbiome were driven from genome-wide association study (GWAS). Using individual level genotype data from UK Biobank, we then calculated the polygenetic risk scoring (PRS) of 114 gut microbiome related traits. Moreover, regression analysis was conducted to evaluate the possible effect of interaction between gut microbiome and CRP on the risks of Patient Health Questionnaire-9 (PHQ-9) (N = 113693) and Generalized Anxiety Disorder-7 (GAD-7) (N = 114219). At last, 11 candidate CRP× gut microbiome interacting were detected for PHQ-9 score, such as F_Ruminococcaceae (β=-0.009, P=2.2×10-3), G_Akkermansia (β=-0.008, P=7.60×10-3), F_Acidaminococcaceae (β=0.008, P=1.22×10-2), G_Holdemanella (β=-0.007, P=1.39×10-2) and O_Lactobacillales (β=0.006，P=1.79×10-2). 16 candidate CRP ×gut microbiome interacting were detected for GAD-7 score, such as O_Bacteroidales (β=0.010, P=4.00×10-4), O_Selenomonadales (β=-0.010, P=1.20×10-3), O_Clostridiales (β=0.009, P=2.70×10-3) and G_Holdemanella (β= -0.008, P=4.20×10-3). Our results support the significant effect of interaction between CRP and gut microbiome on the risks of anxiety and depression, and identified several candidate gut microbiome for them.

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“…Moreover, the recent progress in the understanding of phages and in the methods of their genetic modification may soon make construction of engineered phages a routine procedure rather than a tedious scientific undertaking. Additionally, the new discoveries concerning the interaction of phages with bacteria inside the human body and the effect of phages on human health via their influence on the microbiome open up new possibilities of therapeutic application of modified phages not only to treat infections with bacterial pathogens, but also to improve the conditions of patients suffering from diverse disorders related to a dysfunctional microbiome, by in situ microbiome engineering [ 69 , 71 – 73 , 156 – 159 ].…”

Section: Engineered Phages As Future Therapeutic Options: Rationale and Perspectivesmentioning

confidence: 99%

Engineered Bacteriophage Therapeutics: Rationale, Challenges and Future

2021

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The current problems with increasing bacterial resistance to antibacterial therapies, resulting in a growing frequency of incurable bacterial infections, necessitates the acceleration of studies on antibacterials of a new generation that could offer an alternative to antibiotics or support their action. Bacteriophages (phages) can kill antibiotic-sensitive as well as antibiotic-resistant bacteria, and thus are a major subject of such studies. Their efficacy in curing bacterial infections has been demonstrated in in vivo experiments and in the clinic. Unlike antibiotics, phages have a narrow range of specificity, which makes them safe for commensal microbiota. However, targeting even only the most clinically relevant strains of pathogenic bacteria requires large collections of well characterized phages, whose specificity would cover all such strains. The environment is a rich source of diverse phages, but due to their complex relationships with bacteria and safety concerns, only some naturally occurring phages can be considered for therapeutic applications. Still, their number and diversity make a detailed characterization of all potentially promising phages virtually impossible. Moreover, no single phage combines all the features required of an ideal therapeutic agent. Additionally, the rapid acquisition of phage resistance by bacteria may make phages already approved for therapy ineffective and turn the search for environmental phages of better efficacy and new specificity into an endless race. An alternative strategy for acquiring phages with desired properties in a short time with minimal cost regarding their acquisition, characterization, and approval for therapy could be based on targeted genome modifications of phage isolates with known properties. The first example demonstrating the potential of this strategy in curing bacterial diseases resistant to traditional therapy is the recent successful treatment of a progressing disseminated Mycobacterium abscessus infection in a teenage patient with the use of an engineered phage. In this review, we briefly present current methods of phage genetic engineering, highlighting their advantages and disadvantages, and provide examples of genetically engineered phages with a modified host range, improved safety or antibacterial activity, and proven therapeutic efficacy. We also summarize novel uses of engineered phages not only for killing pathogenic bacteria, but also for in situ modification of human microbiota to attenuate symptoms of certain bacterial diseases and metabolic, immune, or mental disorders.

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Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders

Cited by 244 publications

References 42 publications

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.

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.

Assessing the Effect of Interaction Between C-Reactive Protein and Gut Microbiome on the Risks of Anxiety and Depression

Engineered Bacteriophage Therapeutics: Rationale, Challenges and Future

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