Trillions of microbes reside in the human body and participate in multiple physiological and pathophysiological processes that affect host health throughout the life cycle. The microbiome is hallmarked by distinctive ...Trillions of microbes reside in the human body and participate in multiple physiological and pathophysiological processes that affect host health throughout the life cycle. The microbiome is hallmarked by distinctive compositional and functional features across different life periods.Accumulating evidence has shown that microbes residing in the human body may play fundamental roles in infant development and the maturation of the immune system. Gut microbes are thought to be essential for the facilitation of infantile and childhood development and immunity by assisting in breaking down food substances to liberate nutrients, protecting against pathogens, stimulating or modulating the immune system, and exerting control over the hypothalamic–pituitary–adrenal axis.This review aims to summarize the current understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the role of intestinal microbes in pediatric diseases. Furthermore, we also discuss the microbiota-mediated therapeutics that can reconfigure bacterial communities to treat dysbiosis.展开更多
With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterati...With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.展开更多
The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental p...The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery.When the double-edged neuroinflammatory response is overloaded,it no longer has the protective function of promoting neuroregeneration.Notably,microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology,causing microbiome–gut–brain axis dysregulation from the bottom-up.When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability,peripheral immune cells are recruited to the brain.This results in amplification of neuroinflammatory circuits in the brain,which eventually leads to specific neurological disorders.Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders,which can lead to potential protective effects in the CNS.Accordingly,this study investigated the mutual effects of microbiota and the gut–brain axis,which may provide targeting strategies for future disease treatment.展开更多
The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically revie...The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos. 81671504 and 81401248)the Sanming Project of Medicine in Shenzhen, China (Grant No. SZSM201606088)
文摘Trillions of microbes reside in the human body and participate in multiple physiological and pathophysiological processes that affect host health throughout the life cycle. The microbiome is hallmarked by distinctive compositional and functional features across different life periods.Accumulating evidence has shown that microbes residing in the human body may play fundamental roles in infant development and the maturation of the immune system. Gut microbes are thought to be essential for the facilitation of infantile and childhood development and immunity by assisting in breaking down food substances to liberate nutrients, protecting against pathogens, stimulating or modulating the immune system, and exerting control over the hypothalamic–pituitary–adrenal axis.This review aims to summarize the current understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the role of intestinal microbes in pediatric diseases. Furthermore, we also discuss the microbiota-mediated therapeutics that can reconfigure bacterial communities to treat dysbiosis.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Foundation,No.22HHXBSS00047(to PL)Graduate Science and Technology Innovation Project of Tianjin,No.2022BKY173(to LZ)Tianjin Municipal Science and Technology Bureau Foundation,No.20201194(to PL).
文摘With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.
文摘The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery.When the double-edged neuroinflammatory response is overloaded,it no longer has the protective function of promoting neuroregeneration.Notably,microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology,causing microbiome–gut–brain axis dysregulation from the bottom-up.When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability,peripheral immune cells are recruited to the brain.This results in amplification of neuroinflammatory circuits in the brain,which eventually leads to specific neurological disorders.Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders,which can lead to potential protective effects in the CNS.Accordingly,this study investigated the mutual effects of microbiota and the gut–brain axis,which may provide targeting strategies for future disease treatment.
基金supported by Yuan Du Scholars,Clinical Research Center of Affiliated Hospital of Shandong Second Medical University,No.2022WYFYLCYJ02Weifang Key Laboratory,Weifang Science and Technology Development Plan Project Medical Category,No.2022YX093.
文摘The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.
