机构地区:[1]Department of Internal Medicine,Gastroenterology and Hepatology,Sechenov University,Moscow,Russia [2]Post-Genomic Research Laboratory,Engelhardt Institute of Molecular Biology,Russian Academy of Sciences,Moscow,Russia [3]V.A.Nasonova Research Institute of Rheumatology,Moscow,Russia [4]Consultative and Diagnostic Center 2 of the Moscow Health Department,Moscow,Russia [5]First Hospital Surgery Department,Pirogov Russian National Research Medical University,Moscow,Russia [6]Department of Clinical Laboratory Diagnostics,FGBOU DPO“Russian Medical Academy of Continuing Professional Education of the Ministry of Health of the Russian Federation”,Moscow,Russia [7]The Interregional Public Organization“Scientific Community for the Promotion of the Clinical Study”,Moscow,Russia
出 处:《Journal of Clinical and Translational Hepatology》2024年第8期689-700,共12页临床与转化肝病杂志(英文版)
基 金:supported by the Biocodex Microbiota Foundation(National Research Grant Russia 2019).The sponsor did not participate in the development of the study design,influence the conduct of the study,data analysis,or the decision to publish.
摘 要:Background and Aims:Gut dysbiosis and abnormal cytokine profiles are common in cirrhosis.This study aimed to evaluate the correlations between them.Methods:In the blood plasma of cirrhosis patients and controls,27 cytokines were examined using a multiplex assay.The plasma levels of nitrites(stable metabolites of the endothelial dysfunction biomarker nitric oxide)and lipopolysaccharide(LPS)were examined.The fecal microbiota was assessed by 16S rRNA gene sequencing.Results:Levels of IL-1b,IL-2,IL-6,IL-13,IP-10,IFN-g,TNF-a,LPS,and nitrites were higher in cirrhosis patients than in controls,while levels of IL-4,IL-7,and PDGF-BB were lower.The LPS level was directly correlated with the levels of IL-1b,IL1-Ra,IL-9,IL-17,PDGF-BB,IL-6,TNF-a,and nitrites.The nitrite level was significantly directly correlated with the levels of TNF-a,GM-CSF,IL-17,and IL-12,and inversely correlated with the IL-7 level.TNF-a levels were directly correlated with ascites severity and the abundance of Negativicutes,Enterobacteriaceae,Veillonellaceae,and Klebsiella,while inversely correlated with the abundance of Firmicutes,Clostridia,and Subdoligranulum.IFN-g levels were directly correlated with the abundance of Bacteroidaceae,Lactobacillaceae,Bacteroides,and Megasphaera,and inversely correlated with the abundance of Verrucomicrobiota,Akkermansiaceae,Coriobacteriaceae,Akkermansia,Collinsella,and Gemella.IL-1b levels were directly correlated with the abundance of Comamonadaceae and Enterobacteriaceae and inversely correlated with the abundance of Marinifilaceae and Dialister.IL-6 levels were directly correlated with the abundance of Enterobacteriaceae,hepatic encephalopathy,and ascites severity,and inversely correlated with the abundance of Peptostreptococcaceae,Streptococcaceae,and Streptococcus.Conclusions:The abundance of harmful gut microbiota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.
关 键 词:ENDOTOXIN Leaky gut Gut microbiome Systemic inflammation Gut-liver axis ENDOTOXEMIA
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