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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 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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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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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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Immune disorders and rheumatologic manifestations of viral hepatitis

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World Journal of Gastroenterology 2021年第18期27卷 2073-2089页

作者： Roman Maslennikov Vladimir Ivashkin irina efremova 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 1 Сonsultative and Diagnostic Center 2 of the Moscow City Health DepartmentMoscow 107564Russia

Infection with hepatotropic viruses is not limited to the liver and can lead to the development of various immunological disorders(the formation of cryoglobulins,rheumatoid factor,antinuclear antibodies,autoantibodies specific for autoimmune hepatitis and primary biliary cholangitis,and others),which can manifest as glomerulonephritis,arthritis,uveitis,vasculitis(cryoglobulinemic vasculitis,polyarteritis nodosa,Henoch-Schonlein purpura,isolated cutaneous necrotizing vasculitis),and other rheumatologic disorders,and be a trigger for the subsequent development of autoimmune hepatitis and primary biliary cholangitis.A further study of the association between autoimmune liver diseases and hepatotropic virus infection would be useful to assess the results of treatment of these associated diseases with antiviral *** relationship of these immune disorders and their manifestations with hepatotropic viruses is best studied for chronic hepatitis B and *** isolated cases of these associations are described for hepatitis *** links are least studied,and are often controversial for hepatitis E,possibly due to their relatively rare *** with uveitis,glomerulonephritis,arthritis,vasculitis,autoimmune liver diseases should be tested for biomarkers of viral hepatitis,and if present,these patients should be treated with antiviral drugs.

关键词： Hepatitis A Hepatitis B Hepatitis C Hepatitis E Vasculitis Rheumatoid factor

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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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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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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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Role of intergenic interactions among folate cycle genes in the development of fetal growth retardation

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Reproductive and Developmental Medicine 2023年第1期7卷 32-37页

作者： Olesya efremova irina Ponomarenko Mikhail Churnosov Department of Biomedical Disciplines Belgorod State University308015 BelgorodRussia

Objective:Metabolic disturbances in the folate cycle in mothers can lead to fetal growth retardation(FGR).This study was to analyze the role of intergenic interactions among maternal folate cycle genes in the development of ***:This case-control study recruited 365 women in the third trimester of pregnancy,including 122 FGR patients and 243 *** women were genotyped for 5 polymorphisms of the 4 folate cycle genes:MTR(rs1805087),MTRR(rs1801394),serine hydroxymethyl transferase(SHMT1;rs1979277),and TYMS(rs699517 and rs2790).The SNP×SNP interactions in the two-,three-,and four-locus models were analyzed using the multifactor dimensionality reduction method and a modification of it(the model-based multifactor dimensionality reduction method).Results:Four loci of maternal folate cycle genes(rs1805087 MTR,rs2790 TYMS,rs1801394 MTRR,and rs1979277 SHMT1)were associated with FGR in 3 significant models of single nucleotide polymorphism(SNP)×SNP interactions(two-,three-,and four-locus models)(P<0.05).The highest contribution to FGR was made by polymorphic loci rs1979277 SHMT1(1.70%of entropy),rs1805087 MTR(0.96%),and interactions between rs1979277 SHMT1×rs1805087 MTR(-1.11%)and rs1801394 MTRR×rs1979277 SHMT1(-0.64%).The four-locus maternal genotype combination AG rs1801394 MTRR×AA rs1805087 MTR×CT rs1979277 SHMT1×AG rs2790 TYMS was associated with an increased risk of FGR(β=2.69,P=0.012).FGR-associated SNPs were correlated with the expression of 16 genes(MTR,MTRR,SHMT1,ALKBH5,CTD-2303H24.2,ENOSF1,FAM106A,FOXO3B,LGALS9C,LLGL1,MIEF2,NOS2P2,RP11-806L2.6,SMCR8,TOP3A,and USP32P2)in various tissues and organs related to FGR ***:SNP×SNP interactions of maternal folate cycle genes(MTR,MTRR,SHMT1,and TYMS)are associated with the development of FGR.

关键词： Polymorphism Associations Fetal growth retardation Folate SNP×SNP interactions

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Research on the HIP 18856 binary system

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Research in Astronomy and Astrophysics 2021年第3期21卷 69-72页

作者： Polina efremova Arina Mitrofanova Vladimir Dyachenko Anatoly Beskakotov Alexander Maksimov Denis Rastegaev Yury BalegaSergey Komarinsky Kazan Federal University Kazan 420008Russia Special Astrophysical Observatory of the Russian Academy of Sciences Nizhnij ArkhyzRussia 369167

The results of a study on the binary HIP 18856 and construction of its orbit are *** observational data were obtained at the BTA of SAO RAS in ***,Cvetkovic et *** the orbit for this ***,it is based on six measurements,which cover a small part of the *** positional parameters of the ESA astrometric satellite Hipparcos published speckle interferometric data(Mason et al.,Balega et al.,Horch et al.)and new ones were used in this *** on the new orbital parameters,the mass sum was calculated and the physical parameters of the components were *** obtained orbital and fundamental parameters were compared with the data from the study by Cvetkovic et al..The comparison shows that the new orbital solution is better than the old one,since it fits new observational data *** based on a qualitative evaluation performed by Worley&Heintz,the new orbit was classified as"reliable",which means data cover more than half of the orbit with sufficient quantities of residuals of measurements.

关键词： techniques:high angular resolution,speckle interferometry stars:low-mass,fundamental parameters stars:binaries:spectroscopic stars:individual:HIP 18856

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