Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investig...Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.展开更多
The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases....The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.展开更多
BACKGROUND The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis.Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease(NAFLD)by modul...BACKGROUND The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis.Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease(NAFLD)by modulating gut microbiota.Partially hydrolyzed guar gum(PHGG),a water-soluble dietary fiber,has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndromes.However,its effects on NAFLD remain to be fully elucidated.To determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis.METHODS Seven-week-old male C57BL/6J mice with increased intestinal permeability were fed a control or atherogenic(Ath)diet(a mouse model of NAFLD)for 8 wk,with or without 5%PHGG.Increased intestinal permeability was induced through chronic intermittent administration of low-dose dextran sulfate sodium.Body weight,liver weight,macroscopic findings in the liver,blood biochemistry[aspartate aminotransferase(AST)and alanine aminotransferase(ALT),total cholesterol,triglyceride,free fatty acids,and glucose levels],liver histology,myeloperoxidase activity in liver tissue,mRNA expression in the liver and intestine,serum endotoxin levels in the portal vein,intestinal permeability,and microbiota and short-chain fatty acid(SCFA)profiles in the cecal samples were investigated.RESULTS Mice with increased intestinal permeability subjected to the Ath diet showed significantly increased serum AST and ALT levels,liver fat accumulation,liver inflammatory(tumor necrosis factor-αand monocyte chemotactic protein-1)and fibrogenic(collagen 1a1 andαsmooth muscle actin)marker levels,and liver myeloperoxidase activity,which were significantly attenuated by PHGG treatment.Furthermore,the Ath diet combined with increased intestinal permeability resulted in elevated portal endotoxin levels and activated toll-like receptor(TLR)4 and TLR9 expression,confirming that intestinal permeability was significantly elevated,as observed by evaluating the lumen-to-blood clearance of fluorescein isothiocyanate-conjugated dextran.PHGG treatment did not affect fatty acid metabolism in the liver.However,it decreased lipopolysaccharide signaling through the gut-liver axis.In addition,it significantly increased the abundance of cecal Bacteroides and Clostridium subcluster XIVa.Treatment with PHGG markedly increased the levels of SCFAs,particularly,butyric acid,acetic acid,propionic acid,and formic acid,in the cecal samples.CONCLUSION PHGG partially prevented NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles.展开更多
Methamphetamine(Meth)abuse can cause serious mental disorders,including anxiety and depression.The gut microbiota is a crucial contributor to maintaining host mental health.Here,we aim to investigate if microbiota par...Methamphetamine(Meth)abuse can cause serious mental disorders,including anxiety and depression.The gut microbiota is a crucial contributor to maintaining host mental health.Here,we aim to investigate if microbiota participate in Meth-induced mental disorders,and the potential mechanisms involved.Here,15 mg/kg Meth resulted in anxiety-and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor(SIGMAR1)/BDNF/TRKB pathway in the hippocampus.Mean-while,Meth impaired gut homeostasis by arousing the Toll-like receptor 4(TLR4)-related colonic inflammation,disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids(SCFAs).Moreover,fecal microbiota from Meth-administrated mice mediated the colonic inflam-mation and reproduced anxiety-and depression-like behaviors in recipients.Further,SCFAs supple-mentation optimized Meth-induced microbial dysbiosis,ameliorated colonic inflammation,and repressed anxiety-and depression-like behaviors.Finally,Sigmarl knockout(Sigmar1^(-/-))repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure,and elim-inated the anti-anxiety and-depression effects of SCFAs.The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety-and depression-like behaviors.Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis,and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner.This study confirms the crucial role of microbiota in Methrelated mental disorders and provides a potential preemptive therapy.展开更多
“脾为之卫”理论涵盖了脾主运化、脾主升清、藏营主意等生理功能,而肠道菌群与中医学“脾为之卫”职能有极大的相似性。肠道菌群可通过多种途径参与2型糖尿病(diabetes mellitus type 2,T2DM)的发生过程,其作用机制与代谢产物、激素分...“脾为之卫”理论涵盖了脾主运化、脾主升清、藏营主意等生理功能,而肠道菌群与中医学“脾为之卫”职能有极大的相似性。肠道菌群可通过多种途径参与2型糖尿病(diabetes mellitus type 2,T2DM)的发生过程,其作用机制与代谢产物、激素分泌、免疫反应及细菌-肠-脑轴密切相关。调控肠道菌群中有益菌的数量、种类等,或直接调节短链脂肪酸、脂多糖、胆汁酸等代谢产物的合成与分泌,激活肠道L细胞调节胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)和内分泌调节肽的分泌量,维持葡萄糖稳态,并促进B细胞增殖,增加胰岛素分泌、减弱肠上皮内淋巴细胞炎症反应,提高固有层淋巴细胞活性,从而缓解炎症反应,减轻胰岛素抵抗。展开更多
基金supported by fund from the National Natural Science Foundation of China (32172322)Shandong Provincial Natural Science Foundation (ZR2023QC291)Shandong Traditional Chinese Medicine Technology Project (Q-2023130)。
文摘Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.
基金Supported by the Lejoie-Lake Fellowship(to Camara-Lemarroy CR)awarded by the Hotchkiss Brain Institute
文摘The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.
基金Scientific Research(KAKENHI)(C),No.25460958Japan Society for the Promotion of Science,No.20K11513and Adaptable and Seamless Technology Transfer Program through target driven R&D from the Japan Agency for Medical Research and Development.
文摘BACKGROUND The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis.Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease(NAFLD)by modulating gut microbiota.Partially hydrolyzed guar gum(PHGG),a water-soluble dietary fiber,has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndromes.However,its effects on NAFLD remain to be fully elucidated.To determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis.METHODS Seven-week-old male C57BL/6J mice with increased intestinal permeability were fed a control or atherogenic(Ath)diet(a mouse model of NAFLD)for 8 wk,with or without 5%PHGG.Increased intestinal permeability was induced through chronic intermittent administration of low-dose dextran sulfate sodium.Body weight,liver weight,macroscopic findings in the liver,blood biochemistry[aspartate aminotransferase(AST)and alanine aminotransferase(ALT),total cholesterol,triglyceride,free fatty acids,and glucose levels],liver histology,myeloperoxidase activity in liver tissue,mRNA expression in the liver and intestine,serum endotoxin levels in the portal vein,intestinal permeability,and microbiota and short-chain fatty acid(SCFA)profiles in the cecal samples were investigated.RESULTS Mice with increased intestinal permeability subjected to the Ath diet showed significantly increased serum AST and ALT levels,liver fat accumulation,liver inflammatory(tumor necrosis factor-αand monocyte chemotactic protein-1)and fibrogenic(collagen 1a1 andαsmooth muscle actin)marker levels,and liver myeloperoxidase activity,which were significantly attenuated by PHGG treatment.Furthermore,the Ath diet combined with increased intestinal permeability resulted in elevated portal endotoxin levels and activated toll-like receptor(TLR)4 and TLR9 expression,confirming that intestinal permeability was significantly elevated,as observed by evaluating the lumen-to-blood clearance of fluorescein isothiocyanate-conjugated dextran.PHGG treatment did not affect fatty acid metabolism in the liver.However,it decreased lipopolysaccharide signaling through the gut-liver axis.In addition,it significantly increased the abundance of cecal Bacteroides and Clostridium subcluster XIVa.Treatment with PHGG markedly increased the levels of SCFAs,particularly,butyric acid,acetic acid,propionic acid,and formic acid,in the cecal samples.CONCLUSION PHGG partially prevented NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles.
基金supported by the National Natural Science Foundation of China under Grant No.82171877the Department of Science and Technology of Guangzhou city under Grant No.202002030043(China)the Guangdong Natural Science Foundation under Grant No.2021A1515012456(China).
文摘Methamphetamine(Meth)abuse can cause serious mental disorders,including anxiety and depression.The gut microbiota is a crucial contributor to maintaining host mental health.Here,we aim to investigate if microbiota participate in Meth-induced mental disorders,and the potential mechanisms involved.Here,15 mg/kg Meth resulted in anxiety-and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor(SIGMAR1)/BDNF/TRKB pathway in the hippocampus.Mean-while,Meth impaired gut homeostasis by arousing the Toll-like receptor 4(TLR4)-related colonic inflammation,disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids(SCFAs).Moreover,fecal microbiota from Meth-administrated mice mediated the colonic inflam-mation and reproduced anxiety-and depression-like behaviors in recipients.Further,SCFAs supple-mentation optimized Meth-induced microbial dysbiosis,ameliorated colonic inflammation,and repressed anxiety-and depression-like behaviors.Finally,Sigmarl knockout(Sigmar1^(-/-))repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure,and elim-inated the anti-anxiety and-depression effects of SCFAs.The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety-and depression-like behaviors.Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis,and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner.This study confirms the crucial role of microbiota in Methrelated mental disorders and provides a potential preemptive therapy.
文摘“脾为之卫”理论涵盖了脾主运化、脾主升清、藏营主意等生理功能,而肠道菌群与中医学“脾为之卫”职能有极大的相似性。肠道菌群可通过多种途径参与2型糖尿病(diabetes mellitus type 2,T2DM)的发生过程,其作用机制与代谢产物、激素分泌、免疫反应及细菌-肠-脑轴密切相关。调控肠道菌群中有益菌的数量、种类等,或直接调节短链脂肪酸、脂多糖、胆汁酸等代谢产物的合成与分泌,激活肠道L细胞调节胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)和内分泌调节肽的分泌量,维持葡萄糖稳态,并促进B细胞增殖,增加胰岛素分泌、减弱肠上皮内淋巴细胞炎症反应,提高固有层淋巴细胞活性,从而缓解炎症反应,减轻胰岛素抵抗。
