Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literat...Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of＂gut microbiota＂,＂gut-brain axis＂,and ＂neuroscience＂.Study Selection：All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results：It is well-recognized that gut microbiota affects the brain＆#39;s physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain＆#39;s neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions：Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.展开更多
Parkinson's disease(PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that th...Parkinson's disease(PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological,neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding.Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gutmicrobiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.展开更多
The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and ...The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.展开更多
ProBiotic-4 is a probiotic preparation composed of Bifidobacterium lactis,Lactobacillus casei,Bifidobacterium bifidum,and Lactobacillus acidophilus.This study aims to investigate the effects of ProBiotic-4 on the micr...ProBiotic-4 is a probiotic preparation composed of Bifidobacterium lactis,Lactobacillus casei,Bifidobacterium bifidum,and Lactobacillus acidophilus.This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits,and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8(SAMP8)mice.ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks.We observed that ProBiotic-4 significantly improved the memory deficits,cerebral neuronal and synaptic injuries,glial activation,and microbiota composition in the feces and brains of aged SAMP8 mice.ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier,decreased interleukin-6 and tumor necrosis factor-αat both mRNA and protein levels,reduced plasma and cerebral lipopolysaccharide(LPS)concentration,toll-like receptor 4(TLR4)expression,and nuclear factor-κB(NF-κB)nuclear translocation in the brain.In addition,not only did ProBiotic-4 significantly decreased the levels ofγ-H2 AX,8-hydroxydesoxyguanosine,and retinoic-acid-inducible gene-I(RIG-I),it also abrogated RIG-I multimerization in the brain.These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging,and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-κB signaling pathway and inflammatory responses.展开更多
In China, acupuncture has been considered an effective method for treating gastrointestinal(GI) dysfunction diseases for thousands of years. In fact, acupuncture has gained progressive acceptance from both practitione...In China, acupuncture has been considered an effective method for treating gastrointestinal(GI) dysfunction diseases for thousands of years. In fact, acupuncture has gained progressive acceptance from both practitioners and patients worldwide. However, the therapeutic effects and underlying mechanisms in treating GI dysfunction have not yet been established due to a lack of systematic and comprehensive review articles. Therefore, the aim of this review is to discuss the efficacy of acupuncture as a treatment for GI dysfunction and the associated underlying mechanisms. A search of Pub Med was conducted for articles that were published over the past 10 years using the terms "acupuncture", "gastrointestine", and other relevant keywords. In the following review, we describe the effect and underlying mechanisms of acupuncture on GI function from the perspectives of GI motility, visceral sensitivity, the GI barrier, and the brain-gut axis. The dual regulatory effects of acupuncture may manifest by promoting gastric peristalsis in subjects with low initial gastric motility, and suppressing peristalsis in subjects with active initial motility. In addition, the regulation of acupuncture on gastric motility may be intensitydependent. Our findings suggest that further studies are needed to investigate the effects and more systematic mechanisms in treating GI dysfunction, and to promote the application of acupuncture for the treatment of GI diseases.展开更多
Fecal microbiota transplantation(FMT)is a promising strategy that involves reconstruction of gut microbiota.Recently,it has been considered as a treatment of Crohn’s disease(CD)and certain neurological diseases.Here,...Fecal microbiota transplantation(FMT)is a promising strategy that involves reconstruction of gut microbiota.Recently,it has been considered as a treatment of Crohn’s disease(CD)and certain neurological diseases.Here,to the best of our knowledge,we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy.During the 20 mo of follow-up,FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs.Furthermore,this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.展开更多
The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology.The liver is a central immunological organ that is particularly enriched in innate immune c...The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology.The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota.The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens.Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases.Of immense importance is the step from high-throughput sequencing(correlation)to mechanistic studies(causality)and therapeutic intervention.Here,we review the gut microbiota,liver immunology,and the interaction between the gut and liver.In addition,the impairment in the gut-liver axis found in various liver diseases is reviewed here,with an emphasis on alcohol-associated liver disease(ALD),nonalcoholic fatty liver disease(NAFLD),and autoimmune liver disease(AILD).On the basis of growing evidence from these preclinical studies,we propose that the gut-liver axis paves the way for targeted therapeutic modalities for liver diseases.展开更多
A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels ...A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.展开更多
基金This study was supported by grants from Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support （No. XMLX201401）, the National Natural Science Foundation of China （No. 81301138）, National High-Tech R＆D Program of China （863 Program, No. 2015AA020514）, National Hundred, Thousand, and Ten Thousand Talents Project of Beijing （No. 2010-005）.
文摘Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of＂gut microbiota＂,＂gut-brain axis＂,and ＂neuroscience＂.Study Selection：All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results：It is well-recognized that gut microbiota affects the brain＆#39;s physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain＆#39;s neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions：Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.
文摘Parkinson's disease(PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological,neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding.Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gutmicrobiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.
基金Supported by(in part)FARB-ex 60%2012 of the University of Salerno grant to Vajro P
文摘The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.
基金supported by the National Natural Science Foundation of China(81473219 and 81973307)partly by 111 Project of the National Ministry of Education(B18035,China).
文摘ProBiotic-4 is a probiotic preparation composed of Bifidobacterium lactis,Lactobacillus casei,Bifidobacterium bifidum,and Lactobacillus acidophilus.This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits,and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8(SAMP8)mice.ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks.We observed that ProBiotic-4 significantly improved the memory deficits,cerebral neuronal and synaptic injuries,glial activation,and microbiota composition in the feces and brains of aged SAMP8 mice.ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier,decreased interleukin-6 and tumor necrosis factor-αat both mRNA and protein levels,reduced plasma and cerebral lipopolysaccharide(LPS)concentration,toll-like receptor 4(TLR4)expression,and nuclear factor-κB(NF-κB)nuclear translocation in the brain.In addition,not only did ProBiotic-4 significantly decreased the levels ofγ-H2 AX,8-hydroxydesoxyguanosine,and retinoic-acid-inducible gene-I(RIG-I),it also abrogated RIG-I multimerization in the brain.These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging,and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-κB signaling pathway and inflammatory responses.
基金Supported by National Natural Science Foundation of China,No.81222050 and No.81303122Beijing Natural Science Foundation,No.7144215+1 种基金Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support,No.ZYLX201412financially supported by 973 Program under Grant,No.2014CB543203
文摘In China, acupuncture has been considered an effective method for treating gastrointestinal(GI) dysfunction diseases for thousands of years. In fact, acupuncture has gained progressive acceptance from both practitioners and patients worldwide. However, the therapeutic effects and underlying mechanisms in treating GI dysfunction have not yet been established due to a lack of systematic and comprehensive review articles. Therefore, the aim of this review is to discuss the efficacy of acupuncture as a treatment for GI dysfunction and the associated underlying mechanisms. A search of Pub Med was conducted for articles that were published over the past 10 years using the terms "acupuncture", "gastrointestine", and other relevant keywords. In the following review, we describe the effect and underlying mechanisms of acupuncture on GI function from the perspectives of GI motility, visceral sensitivity, the GI barrier, and the brain-gut axis. The dual regulatory effects of acupuncture may manifest by promoting gastric peristalsis in subjects with low initial gastric motility, and suppressing peristalsis in subjects with active initial motility. In addition, the regulation of acupuncture on gastric motility may be intensitydependent. Our findings suggest that further studies are needed to investigate the effects and more systematic mechanisms in treating GI dysfunction, and to promote the application of acupuncture for the treatment of GI diseases.
基金Supported by The Public Donated Grant"Intestine Initiative"National Nature Science Foundation of China,No.81670495
文摘Fecal microbiota transplantation(FMT)is a promising strategy that involves reconstruction of gut microbiota.Recently,it has been considered as a treatment of Crohn’s disease(CD)and certain neurological diseases.Here,to the best of our knowledge,we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy.During the 20 mo of follow-up,FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs.Furthermore,this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.
基金supported in part by the National Natural Science Foundation of China(grants#81830016,81771732,and 81620108002 to X.M.,#81922010 and 81873561 to R.T.)supported in part by services provided by the NIH centers P30 DK120515 and P50 AA011999+1 种基金supported by the excellence initiative VASCage(Centre for Promoting Vascular Health in the Ageing Community)R8fD K-Centre(COMET program-Competence Centers for Excellent Technologies)funded by the Austrian Ministry for Transport,Innovation and Technology,the Austrian Ministry for Digital and Economic Affairs and the federal states Tyrol,Salzburg and Vienna.
文摘The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology.The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota.The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens.Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases.Of immense importance is the step from high-throughput sequencing(correlation)to mechanistic studies(causality)and therapeutic intervention.Here,we review the gut microbiota,liver immunology,and the interaction between the gut and liver.In addition,the impairment in the gut-liver axis found in various liver diseases is reviewed here,with an emphasis on alcohol-associated liver disease(ALD),nonalcoholic fatty liver disease(NAFLD),and autoimmune liver disease(AILD).On the basis of growing evidence from these preclinical studies,we propose that the gut-liver axis paves the way for targeted therapeutic modalities for liver diseases.
文摘A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.
