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Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis

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World Journal of Hepatology 2024年第5期16卷 822-831页

作者： Irina Efremova Roman Maslennikov elena poluektova Oleg Medvedev Anna Kudryavtseva George Krasnov Maria Fedorova Filipp Romanikhin Maria Zharkova Oxana Zolnikova Gyunay Bagieva Vladimir Ivashkin Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia Department of Scientific Scientific Community for the Promotion of the Clinical Study of the Human MicrobiomeMoscow 119435Russia Department of Pharmacology Lomonosov Moscow State UniversityMoscow 119192Russia Department of Post-Genomic Research Laboratory Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscow 119991Russia

BACKGROUND The gut–liver axis and bacterial translocation are important in cirrhosis,but there is no available universal biomarker of cellular bacterial translocation,for which presepsin may be a *** To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious *** This study included 48 patients with Child–Pugh cirrhosis classes B and C and 15 healthy *** fecal microbiome was assessed using 16S rRNA gene *** levels of presepsin were measured.A total of 22 patients received a probiotic(Saccharomyces boulardii)for 3 *** Presepsin levels were higher in patients with cirrhosis than in healthy individuals[342(91-2875)vs 120(102-141)pg/mL;P=0.048].Patients with elevated presepsin levels accounted for 56.3%of all included *** had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child–Pugh *** with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation,namely Bacilli and Proteobacteria(including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas),and a low abundance of bacteria from the family Lachnospiraceae(including the minor genus Fusicatenibacter),which produce short-chain fatty acids that have a positive effect on intestinal barrier *** presepsin level directly correlated with the relative abundance of Bacilli,Proteobacteria,and inversely correlated with the abundance of Lachnospiraceae and *** 3 months of taking the probiotic,the severity of cirrhosis on the Child–Pugh scale decreased significantly only in the group with elevated presepsin levels[from 9(8-11)to 7(6-9);P=0.004],while there were no significant changes in the group with normal presepsin levels[from 8(7-8)to 7(6-8);P=0.123].A high level of presepsin

关键词： Dysbiosis Gut Intestinal permeability Leaky gut Gut-liver axis Liver Microbiota

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Gut-liver axis in cirrhosis:Are hemodynamic changes a missing link?

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World Journal of Clinical Cases 2021年第31期9卷 9320-9332页

作者： Roman Maslennikov Vladimir Ivashkin Irina Efremova elena poluektova elena Shirokova Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia The Interregional Public Organization"Scientific Community for the Promotion of the Clinical Study of the Human Microbiome" Moscow 119435Russia Department of Internal Medicine Consultative and Diagnostic Center of the Moscow City Health DepartmentMoscow 107564Russia

Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially *** introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several *** dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic *** inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer *** majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with ***,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly *** remain a missing link in the gut-liver axis and a challenge for future research.

关键词： Gut microbiota Gut dysbiosis Small intestinal bacterial overgrowth Intestinal barrier Bacterial translocation Vasodilation Hyperdynamic circulation Gut microbiome Cardiac output Systemic vascular resistance

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Gut dysbiosis and small intestinal bacterial overgrowth as independent forms of gut microbiota disorders in cirrhosis

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World Journal of Gastroenterology 2022年第10期28卷 1067-1077页

作者： Roman Maslennikov Vladimir Ivashkin Irina Efremova elena poluektova Anna Kudryavtseva George Krasnov Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia Scientific Community for Human Microbiome Research Moscow 119435Russia Department of Internal Medicine 1 Сonsultative and Diagnostic Center 2 of the Moscow City Health DepartmentMoscow 107564Russia Laboratory of Postgenomic Research Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscow 119991Russia

BACKGROUND Gut dysbiosis and small intestinal bacterial overgrowth(SIBO)are commonly observed in patients with *** the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis,dysbiosis and SIBO were always studied *** To study the relationship of gut dysbiosis and SIBO in *** This observational study included 47 in-patients with *** microbiome was assessed using 16 S r RNA gene *** was assessed using the lactulose hydrogen breath *** SIBO was found in 24/47(51.1%)*** with SIBO had a higher abundance of Firmicutes(P=0.017)and Fusobacteria(P=0.011),and a lower abundance of Bacteroidetes(P=0.013)than patients without *** increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia(P=0.020)of the Lachnospiraceae family(P=0.047),while the abundance of other major families of this phylum[Ruminococcaceae(P=0.856),Peptostreptococcaceae(P=0.066),Clostridiaceae(P=0.463),Eubacteriaceae(P=0.463),Lactobacillaceae(P=0.413),and Veillonellaceae(P=0.632)]did not differ significantly between the patients with and without *** level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum[Bacteroidaceae(P=0.014),Porphyromonadaceae(P=0.002),and Rikenellaceae(P=0.047)],with the exception of Prevotellaceae(P=0.941).There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis[Proteobacteria(P=0.790),Bacilli(P=0.573),Enterobacteriaceae(P=0.632),Streptococcaceae(P=0.170),Staphylococcaceae(P=0.450),and Enterococcaceae(P=0.873)]between patients with and without *** Despite the differences observed in the gut microbiome between patients with and without SIBO,gut dysbiosis and SIBO are most

关键词： Dysbiosis Gut-liver axis Microbiome Small intestinal bacterial overgrowth Cirrhosis Microbiota

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Probiotics in hepatology:An update

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World Journal of Hepatology 2021年第9期13卷 1154-1166页

作者： Roman Maslennikov Vladimir Ivashkin Irina Efremova elena poluektova elena Shirokova Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia Scientific Community for Human Microbiome Research Moscow 119435Russia Department of Internal Medicine Consultative and Diagnostic Center of the Moscow City Health DepartmentMoscow 107564Russia

The gut-liver axis plays an important role in the pathogenesis of various liver *** are living bacteria that may be used to correct disorders of this *** progress has been made in the study of probiotic drugs for the treatment of various liver diseases in the last *** has been proven that probiotics are useful for hepatic encephalopathy,but their effects on other symptoms and syndromes of cirrhosis are poorly *** effectiveness in the treatment of metabolic associated fatty liver disease has been shown both in experimental models and in clinical trials,but their effect on the prognosis of this disease has not been *** beneficial effects of probiotics in alcoholic liver disease have been shown in many experimental studies,but there are very few clinical trials to support these *** effects of probiotics on the course of other liver diseases are either poorly studied(such as primary sclerosing cholangitis,chronic hepatitis B and C,and autoimmune hepatitis)or not studied at all(such as primary biliary cholangitis,hepatitis A and E,Wilson's disease,hemochromatosis,storage diseases,and vascular liver diseases).Thus,despite the progress in the study of probiotics in hepatology over the past decade,there are many unexplored and unclear questions surrounding this topic.

关键词： Gut-liver axis Pathogenesis Gut dysbiosis Gut microbiota Gut microbiome Liver disease Probiotics Hepatic encephalopathy Cirrhosis Metabolic associated fatty liver disease Alcoholic liver disease Primary sclerosing cholangitis

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Antibiotics,gut microbiota,and irritable bowel syndrome:What are the relations?

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World Journal of Gastroenterology 2022年第12期28卷 1204-1219页

作者： Zarina Mamieva elena poluektova Valery Svistushkin Vasily Sobolev Oleg Shifrin Francisco Guarner Vladimir Ivashkin Department of Internal Disease Propaedeutics N.V.Sklifosovsky Institute of Clinical MedicineI.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow 119991Russia Department of Ear Throat and Nose DiseasesN.V.Sklifosovsky Institute of Clinical MedicineI.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow 119991Russia Digestive System Research Unit Vall d’Hebron Research InstituteBarcelona 08035Spain

Irritable bowel syndrome(IBS)is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits(constipation,diarrhea,or both),and it is often accompanied by symptoms of abdominal bloating and *** is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care *** extensive research,the etiology and underlying pathophysiology of IBS remain incompletely *** mechanisms involved in its pathogenesis include increased intestinal permeability,changes in the immune system,visceral hypersensitivity,impaired gut motility,and emotional ***,accumulating evidence has highlighted the important role of the gut microbiota in the development of *** dysbiosis within the gut is thought to contribute to all aspects of its multifactorial *** last few decades have also seen an increasing interest in the impact of antibiotics on the gut ***,antibiotics have been suggested to play a role in the development of *** research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in *** suggestion is further supported by data from cohort and case-control studies,indicating that antibiotic treatment is associated with an increased risk of *** paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.

关键词： Gut microbiota Irritable bowel syndrome Antibiotics Intestinal barrier Gut motility Gut sensitivity

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Effect of probiotics on hemodynamic changes and complications associated with cirrhosis:A pilot randomized controlled trial

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World Journal of Hepatology 2022年第8期14卷 1667-1677页

作者： Roman Maslennikov Irina Efremova Vladimir Ivashkin Maria Zharkova elena poluektova elena Shirokova Konstantin Ivashkin Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia The Scientific Community for Human Microbiome Research Moscow 119435Russia Consultative and Diagnostic Center No.2 of Moscow Health Department Moscow 107764Russia

BACKGROUND Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease *** may reduce bacterial translocation and may therefore be useful to redress the circulatory *** To investigate the effect of probiotics on hemodynamic parameters,systemic inflammation,and complications of cirrhosis in this randomized placebocontrolled *** This single-blind randomized placebo-controlled study included 40 patients with Child-Pugh class B and C cirrhosis;24 patients received probiotics(Saccharomyces boulardii)for 3 mo,and 16 patients received a placebo over the same *** function and the systemic hemodynamic status were evaluated pre-and *** and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic *** output and systemic vascular resistance were *** Following a 3-mo course of probiotics in comparison to the control group,we observed amelioration of hyperdynamic circulation[a decrease in cardiac output(P=0.026)and an increase in systemic vascular resistance(P=0.026)]and systemic inflammation[a decrease in serum C-reactive protein levels(P=0.044)],with improved liver function[an increase in serum albumin(P=0.001)and a decrease in the value of Child-Pugh score(P=0.001)]as well as a reduction in the severity of ascites(P=0.022),hepatic encephalopathy(P=0.048),and cholestasis[a decrease in serum alkaline phosphatase(P=0.016)and serum gamma-glutamyl transpeptidase(P=0.039)activity]and an increase in platelet counts(P<0.001)and serum sodium level(P=0.048).CONCLUSION Probiotic administration was associated with amelioration of hyperdynamic circulation and the associated complications of cirrhosis.

关键词： Gut Gut-liver axis Microbiota Hemodynamics Heart Gut-heart axis Saccharomyces boulardii Portal hypertension

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Gut dysbiosis is associated with poorer long-term prognosis in cirrhosis

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World Journal of Hepatology 2021年第5期13卷 557-570页

作者： Roman Maslennikov Vladimir Ivashkin Irina Efremova Aliya Alieva Ekaterina Kashuh Ekaterina Tsvetaeva elena poluektova elena Shirokova Konstantin Ivashkin Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia The Interregional Public Organization“Scientific Community for the Promotion of the Clinical Study of the Human Microbiome” Moscow 119435Russia

BACKGROUND Gut dysbiosis is common in *** To study the influence of gut dysbiosis on prognosis in *** The case-control study included 48 in-patients with cirrhosis and 21 healthy *** microbiome was assessed using 16S ribosomal ribonucleic acid gene *** used modified dysbiosis ratio(MDR):[Bacilli(%)+Proteobacteria(%)]/[Clostridia(%)+Bacteroidetes(%)].Patients with MDR more the median made up the group with severe dysbiosis,others did the group with nonsevere *** follow-up period was 4 *** The mortality rate of patients with severe dysbiosis was significantly higher than that of patients with non-severe dysbiosis(54.2%vs 12.5%;P=0.001).The presence of severe dysbiosis was independent risk factors for death[hazard ratio=8.6×(1.9-38.0);P=0.005].The abundance of Enterobacteriaceae(P=0.002),Proteobacteria(P=0.002),and Lactobacillaceae(P=0.025)was increased and the abundance of Firmicutes(P=0.025)and Clostridia(P=0.045)was decreased in the deceased patients compared with the *** deceased patients had a higher MDR value than the survivors[0.131×(0.069-0.234)vs 0.034×(0.009-0.096);P=0.004].If we applied an MDR value of 0.14 as the cutoff point,then it predicted patient death within the next year with a sensitivity of 71.4%and a specificity of 82.9%[area under the curve=0.767×(0.559-0.974)].MDR was higher in patients with cirrhosis than in health controls[0.064×(0.017-0.131)vs 0.005×(0.002-0.007);P<0.001],and in patients with decompensated cirrhosis than in patients with compensated cirrhosis[0.106×(0.023-0.211)vs 0.033×(0.012-0.074);P=0.031].MDR correlated negatively with prothrombin(r=-0.295;P=0.042),cholinesterase(r=-0.466;P=0.014)and serum albumin(r=-0.449;P=0.001)level and positively with Child–Turcotte–Pugh scale value(r=0.360;P=0.012).CONCLUSION Gut dysbiosis is associated with a poorer long-term prognosis in cirrhosis.

关键词： Cirrhosis Dysbiosis Gut ROC-analysis Microbiota Microbiome Gut-liver axis

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Epidemiology of small intestinal bacterial overgrowth

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World Journal of Gastroenterology 2023年第22期29卷 3400-3421页

作者： Irina Efremova Roman Maslennikov elena poluektova Ekaterina Vasilieva Yury Zharikov Andrey Suslov Yana Letyagina Evgenii Kozlov Anna Levshina Vladimir Ivashkin Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia The Scientific Community for Human Microbiome Research Moscow 119435Russia Department of Human Anatomy and Histology Sechenov UniversityMoscow 125009Russia N.V.Sklifosovsky Institute of Clinical Medicine Sechenov UniversityMoscow 119991Russia Department of Clinical Immunology and Allergy Sechenov UniversityMoscow 119991Russia

Small intestinal bacterial overgrowth(SIBO)is defined as an increase in the bacterial content of the small intestine above normal *** presence of SIBO is detected in 33.8%of patients with gastroenterological complaints who underwent a breath test,and is significantly associated with smoking,bloating,abdominal pain,and *** pump inhibitor therapy is a significant risk factor for *** risk of SIBO increases with age and does not depend on gender or *** complicates the course of a number of diseases and may be of pathogenetic significance in the development of their *** is significantly associated with functional dyspepsia,irritable bowel syndrome,functional abdominal bloating,functional constipation,functional diarrhea,short bowel syndrome,chronic intestinal pseudo-obstruction,lactase deficiency,diverticular and celiac diseases,ulcerative colitis,Crohn’s disease,cirrhosis,metabolic-associated fatty liver disease(MAFLD),primary biliary cholangitis,gastroparesis,pancreatitis,cystic fibrosis,gallstone disease,diabetes,hypothyroidism,hyperlipidemia,acromegaly,multiple sclerosis,autism,Parkinson’s disease,systemic sclerosis,spondylarthropathy,fibromyalgia,asthma,heart failure,and other *** development of SIBO is often associated with a slowdown in orocecal transit time that decreases the normal clearance of bacteria from the small *** slowdown of this transit may be due to motor dysfunction of the intestine in diseases of the gut,autonomic diabetic polyneuropathy,and portal hypertension,or a decrease in the motor-stimulating influence of thyroid *** a number of diseases,including cirrhosis,MAFLD,diabetes,and pancreatitis,an association was found between disease severity and the presence of *** work on the effect of SIBO eradication on the condition and prognosis of patients with various diseases is required.

关键词： Gut microbiota Gut-liver axis Breath test Lactulose Methane Hydrogen

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Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota

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World Journal of Gastroenterology 2023年第27期29卷 4236-4251页

作者： Roman Maslennikov Aliya Alieva elena poluektova Yury Zharikov Andrey Suslov Yana Letyagina Ekaterina Vasileva Anna Levshina Evgenii Kozlov Vladimir Ivashkin Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia The Scientific Community for Human Microbiome Research Moscow 119435Russia Department of Human Anatomy and Histology Sechenov UniversityMoscow 119435Russia Laboratory of Immunopathology Department of Clinical Immunology and AllergySechenov UniversityMoscow 119991Russia

Decreased muscle mass and function,also known as sarcopenia,is common in patients with cirrhosis and is associated with a poor *** the pathogenesis of this disorder has not been fully elucidated,a disordered gutmuscle axis probably plays an important *** barrier function of the gut and liver,gut dysbiosis,and small intestinal bacterial overgrowth(SIBO)can lead to increased blood levels of ammonia,lipopolysaccharides,pro-inflammatory mediators,and *** factors have complex negative effects on muscle mass and *** interventions that target the gut microbiota(long-term use of rifaximin,lactulose,lactitol,or probiotics)positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia,bacterial translocation,and systemic inflammation and correcting gut dysbiosis and ***,although these drugs are promising,they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with *** data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis;however,the results of animal experimental studies are promising.

关键词： Cirrhosis Muscle Fragility Liver Microbiota Microbiome

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Gut dysbiosis and body composition in cirrhosis

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World Journal of Hepatology 2022年第6期14卷 1210-1225页

作者： Roman Maslennikov Vladimir Ivashkin Aliya Alieva elena poluektova Anna Kudryavtseva George Krasnov Maria Zharkova Yuri Zharikov Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia Scientific Community for Human Microbiome Research Moscow 119435Russia Department of Internal Medicine Сonsultative and Diagnostic Center No.2Moscow City Health DepartmentMoscow 107564Russia Center for Precision Genome Editing and Genetic Technologies for Biomedicine Engelhardt Institute of Molecular BiologyRussian Academy of Sciences119991 MoscowRussia Laboratory of Postgenomic Research Engelhardt Institute of Molecular BiologyRussian Academy of Sciences119991 MoscowRussia Department of Anatomy Sechenov UniversityMoscow 119435Russia

BACKGROUND Gut dysbiosis and changes in body composition(i.e.,a decrease in the proportion of muscle mass and an increase in extracellular fluid)are common in *** To study the relationship between the gut microbiota and body composition in *** This observational study included 46 patients with *** microbiome was assessed using 16S rRNA gene *** bioelectrical impedance analysis was performed to assess body composition in these *** An increase in fat mass and a decrease in body cell mass were noted in 23/46(50.0%)and 15/46(32.6%)patients,*** in the gut microbiome were not independently associated with the fat mass percentage in *** abundance of Bacteroidaceae(P=0.041)and Eggerthella(P=0.001)increased,whereas that of Erysipelatoclostridiaceae(P=0.006),Catenibacterium(P=0.021),Coprococcus(P=0.033),Desulfovibrio(P=0.043),Intestinimonas(P=0.028),and Senegalimassilia(P=0.015)decreased in the gut microbiome of patients with body cell mass *** amount of extracellular fluid increased in 22/46(47.6%)*** abundance(P<0.001)increased,whereas Firmicutes(P=0.023),Actinobacteria(P=0.026),Bacilli(P=0.008),Anaerovoraceceae(P=0.027),Christensenellaceae(P=0.038),Eggerthellaceae(P=0.047),Erysipelatoclostridiaceae(P=0.015),Erysipelotrichaceae(P=0.003),Oscillospiraceae(P=0.024),Rikenellaceae(P=0.002),Collinsella(P=0.030),Hungatella(P=0.040),Peptococcaceae(P=0.023),Slackia(P=0.008),and Senegalimassilia(P=0.024)abundance decreased in these *** with clinically significant ascites(n=9)had a higher abundance of Proteobacteria(P=0.031)and a lower abundance of Actinobacteria(P=0.019)and Bacteroidetes(P=0.046)than patients without clinically significant ascites(n=37).CONCLUSION Changes in the amount of body cell mass and extracellular fluid are associated with changes in the gut microbiome in cirrhosis patients.

关键词： Dysbiosis Microbiome Microbiota Gut-Liver axis Sarcopenia Malnutrition Cirrhosis

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