Disturbances of purine and lipid metabolism in the microbiota-gut-brain axis in male adolescent nonhuman primates with depressive-like behaviors

Teng，Teng1,2; Clarke，Gerard3,4; Wu，Jing2,5; Wu，Qingyuan2,6; Maes，Michael7,8,9; Wang，Jie1,2; Wu，Hongyan1,2; Yin，Bangmin1,2; Jiang，Yuanliang1,2; Li，Xuemei1,2; Liu，Xueer1,2; Han，Ying10; Song，Jinlin11,12; Jin，Xin11,12; Ji，Ping11,12; Guo，Yi13,14; Zhou，Xinyu1,2; Xie，Peng2,5

2023

10.1016/j.jare.2023.04.010

Journal of Advanced Research   Impact Factor & Quartile

2090-1232

Introduction: Major depressive disorder (MDD) in adolescents is a widespread and growing global public health concern with unique characteristics and pathophysiological mechanisms that are distinct from MDD in adults. Objective: The purpose of our work was to address this knowledge gap about the unique characteristics and pathophysiological mechanisms of adolescent depression from a microbiota-gut-brain (MGB) axis perspective. Method: Ten healthy male cynomolgus macaques (Macaca fascicularis) were paired into five pairs based on age and body weight, and two cynomolgus macaques from each pair were randomly allocated to chronic unpredictable mild stress group, or unstressed control group. At endpoint, microbe composition from cecum, ascending colon, transverse colon, and descending colon were analyzed by metagenome sequencing, and the metabolite profiles of MGB axis including central (prefrontal cortex, hippocampus and amygdala) and peripheral (plasma, gut and feces of cecum, ascending colon, transverse colon and descending colon) samples were analyzed by metabolomic profiling. Then, we compare the gut microbiome and metabolic signatures in MGB axis between adolescent and adult depressed macaques. Results: The microbial composition and gut-brain metabolic signatures were widely divergent between adolescent and adult depressed macaques, though the phylum Firmicutes and lipid metabolism pathways were persistently altered in both populations. Purine and arginine biosynthesis metabolism were a specific hallmark of adolescent depressed macaques, while fatty acyl metabolism was specially altered in adult. These differential metabolic pathways in adolescent and adult depressed macaques were mainly mapped into the prefrontal cortex and hippocampus, respectively. Notably, the genus Clostridium and Haemophilus, characteristically disturbed in adolescent depressed macaques but not in adult, were also significantly associated with the majority of purine metabolites in MGB axis. Conclusion: These findings provide a new framework describing divergent pathophysiological mechanisms between adolescent and adult depression, and may open new windows for more effective treatment strategies of adolescent depression.

Adolescent Adult Depression Metabolism Microbiota-gut-brain axis

English

Others

2-s2.0-85152895094

Scopus

1.Department of Psychiatry,The First Affiliated Hospital of Chongqing Medical University,Chongqing,China
2.NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases,The First Affiliated Hospital of Chongqing Medical University,Chongqing,China
3.Department of Psychiatry and Neurobehavioural Science,University College Cork,Cork,Ireland
4.APC Microbiome Ireland,University College Cork,Cork,Ireland
5.Department of Neurology,The First Affiliated Hospital of Chongqing Medical University,Chongqing,China
6.Department of Neurology,Chongqing University Three Gorges Hospital,Chongqing University,Wanzhou,China
7.Department of Psychiatry,Faculty of Medicine,Chulalongkorn University,Bangkok,Thailand
8.Department of Psychiatry,Medical University of Plovdiv,Plovdiv,Bulgaria
9.School of Medicine,IMPACT Strategic Research Centre,Deakin University,Geelong,Australia
10.National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence,Peking University,Beijing,China
11.Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences,Stomatological Hospital of Chongqing Medical University,Chongqing,China
12.Key Laboratory of Psychoseomadsy,Stomatological Hospital of Chongqing Medical University,Chongqing,China
13.Department of Neurology,Shenzhen People's Hospital,The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,China
14.The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,China

Teng，Teng,Clarke，Gerard,Wu，Jing,et al. Disturbances of purine and lipid metabolism in the microbiota-gut-brain axis in male adolescent nonhuman primates with depressive-like behaviors[J]. Journal of Advanced Research,2023.

Teng，Teng.,Clarke，Gerard.,Wu，Jing.,Wu，Qingyuan.,Maes，Michael.,...&Xie，Peng.(2023).Disturbances of purine and lipid metabolism in the microbiota-gut-brain axis in male adolescent nonhuman primates with depressive-like behaviors.Journal of Advanced Research.

Teng，Teng,et al."Disturbances of purine and lipid metabolism in the microbiota-gut-brain axis in male adolescent nonhuman primates with depressive-like behaviors".Journal of Advanced Research (2023).