Preliminary Study On Dyfunction Of Gut Microbes And Lipids In Natural Depressed Monkeys

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 axis in depression.Lipid is one of the main components of the brain,and many neurological diseases are accompanied by disturbed lipid.In previous studies,we found disturbances of lipid in the brain tissues of animal models of depression.Our previously established non-human primate model of naturally occurring depression-like behaviors,which is characterized by microbiota-gut–brain axis disturbances,can be used to interrogate how a disturbed gut ecosystem and lipid may modulate the MDD onset.Purpose : To better clarify the molecular interrelationships and downstream functional consequences in the microbiota-gut–brain axis on MDD pathology,here,gut metagenomics and lipidomics were used to characterize how gut virus and bacterial species,and associated metabolites,change in depressive monkey model.Method:The M.fascicularis were divided into two groups(depressionlike(DL)=6,health control(HC)=6).The metagenomics were used to analyze the feces of the monkeys.The LC-MS were used to analyze the HIP,PFC,AMY and plasma.Then,we analyzed the structure and pathway of lipids,and analyzed the co-occurrence network in combination with altered gut viral and bacterial species.Results: We identified a panel of 33 gut virus and 14 bacterial species that could discriminate the 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,cooccurrence 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 DG levels and structure in the PFC are hallmarks of the DL macaque and correlated with altered gut virus and bacteria,thus providing a new framework for understanding the gut microbiome’s role in depression.