Публикации в журналах, индексируемых в международной базе данных Scopus

14.12.2020

Efficacy and Safety of a Probiotic Containing Saccharomyces boulardii CNCM I-745 in the Treatment of Small Intestinal Bacterial Overgrowth in Decompensated Cirrhosis: Randomized, Placebo-Controlled Study

Irina Efremova, Roman Maslennikov, Zharkova Maria, Poluektova Elena, Nona Benuni, Aleksandr Kotusov, Tatyana Demina, Aleksandra Ivleva, Farida Adzhieva, Taisiya Krylova, Vladimir Ivashkin

Journal of Clinical Medicine

https://doi.org/10.3390/jcm13030919

 Abstract

Background: The aim was to evaluate the effectiveness of the probiotic containing Saccharomyces boulardii in the treatment of small intestinal bacterial overgrowth (SIBO) in patients with decompensated cirrhosis. Methods: This was a blinded, randomized, placebo-controlled study. Results: After 3 months of treatment, SIBO was absent in 80.0% of patients in the probiotic group and in 23.1% of patients in the placebo group (p = 0.002). The patients with eliminated SIBO had decreased frequency of ascites and hepatic encephalopathy, the increased platelets and albumin levels, the decreased blood levels of total bilirubin, biomarkers of bacterial translocation (lipopolysaccharide [LPS]) and systemic inflammation (C-reactive protein), and positive changes in markers of hyperdynamic circulation compared with the state at inclusion. There were no significant changes in the claudin 3 level (the intestinal barrier biomarker) in these patients. No significant changes were observed in the group of patients with persistent SIBO. The serum level of nitrate (endothelial dysfunction biomarker) was lower in patients with eradicated SIBO than in patients with persistent SIBO. One (5.3%) patient with eradicated SIBO and six (42.9%) patients with persistent SIBO died within the first year of follow-up (p = 0.007). Conclusions: SIBO eradication was an independent predictor of a favorable prognosis during the first year of follow-up.

Keywords: probiotics; hemodynamics; gut–liver axis; gut–heart axis; vasodilatation; endotoxemia; liver; microbiota; leaky gut

For citation: Efremova I, Maslennikov R, Zharkova M, Poluektova E, Benuni N, Kotusov A, Demina T, Ivleva A, Adzhieva F, Krylova T, Ivashkin V. Efficacy and Safety of a Probiotic Containing Saccharomyces boulardii CNCM I-745 in the Treatment of Small Intestinal Bacterial Overgrowth in Decompensated Cirrhosis: Randomized, Placebo-Controlled Study. J Clin Med. 2024 Feb 5;13(3):919. doi: 10.3390/jcm13030919. PMID: 38337613; PMCID: PMC10856456.

Gut Dysbiosis and Hemodynamic Changes as Links of the Pathogenesis of Complications of Cirrhosis

Irina Efremova, Roman Maslennikov, Elena Poluektova, Maria Zharkova, Anna Kudryavtseva, George Krasnov, Maria Fedorova, Elena Shirokova, Evgenii Kozlov, Anna Levshina, Vladimir Ivashkin

Microorganisms 

DOI: 10.3390/microorganisms11092202

Abstract

The aim was to evaluate the relationship between gut dysbiosis and hemodynamic changes (hyperdynamic circulation) in cirrhosis, and between hemodynamic changes and complications of this disease. This study included 47 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Echocardiography with a simultaneous assessment of blood pressure and heart rate was performed to assess systemic hemodynamics. Patients with hyperdynamic circulation had more severe cirrhosis, lower albumin, sodium and prothrombin levels, higher C-reactive protein, aspartate aminotransferase and total bilirubin levels, and higher incidences of portopulmonary hypertension, ascites, overt hepatic encephalopathy, hypoalbuminemia, hypoprothrombinemia, systemic inflammation, and severe hyperbilirubinemia than patients with normodynamic circulation. Patients with hyperdynamic circulation compared with those with normodynamic circulation had increased abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Fusobacteria, Micrococcaceae, Intestinobacter, Clostridium sensu stricto, Proteus and Rumicoccus, and decreased abundance of Bacteroidetes, Bacteroidaceae, Holdemanella, and Butyrivibrio. The systemic vascular resistance and cardiac output values correlated with the abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Micrococcaceae, and Fusobacteria. Heart rate and cardiac output value were negatively correlated with the abundance of Bacteroidetes. The mean pulmonary artery pressure value was positively correlated with the abundance of Proteobacteria and Micrococcaceae, and negatively with the abundance of Holdemanella.

Keywords: gut–heart axis; gut–liver axis; microbiome; microbiota; portal hypertension.

Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial

Aleksandra Kovaleva, Elena Poluektova, Roman Maslennikov, Anna Karchevskaya, Oleg Shifrin, Andrey Kiryukhin, Aleksandr Tertychnyy, Leonid Kovalev, Marina Kovaleva, Olga Lobanova, Anna Kudryavtseva, George Krasnov, Maria Fedorova, Vladimir Ivashkin.

Journal of Clinical Medicine 

DOI: 10.3390/jcm12186064

Abstract

Treatment of functional digestive disorders is not always effective. Therefore, a search for new application points for potential drugs is perspective. Our aim is to evaluate the effect of rebamipide on symptom severity, intestinal barrier status, and intestinal microbiota composition and function in patients with diarrheal variant of irritable bowel syndrome overlapping with functional dyspepsia (D-IBSoFD). Sixty patients were randomized to receive trimebutine (TRI group), trimebutine + rebamipide (T + R group), or rebamipide (REB group) for 2 months. At the beginning and end of the study, patients were assessed for general health (SF-36), severity of digestive symptoms (Gastrointestinal Symptom Rating and 7 × 7 scales), state of the intestinal barrier, and composition (16S rRNA gene sequencing) and function (short-chain fatty acid fecal content) of the gut microbiota. The severity of most digestive symptoms was reduced in the REB and T + R groups to levels similar to that observed in the TRI group. The duodenal and sigmoidal lymphocytic and sigmoidal eosinophilic infiltration was decreased only in the REB and T + R groups, not in the TRI group. Serum zonulin levels were significantly decreased only in the REB group. A decrease in intraepithelial lymphocytic infiltration in the duodenum correlated with a decrease in the severity of rumbling and flatulence, while a decrease in infiltration within the sigmoid colon correlated with improved stool consistency and decreased severity of the sensation of incomplete bowel emptying. In conclusion, rebamipide improves the intestinal barrier condition and symptoms in D-IBSoFD. The rebamipide effects are not inferior to those of trimebutine.

Keywords: dysbiosis; functional bowel disease; gut microbiota; intestinal permeability; minimal inflammation.

For citations: Kovaleva A, Poluektova E, Maslennikov R, Karchevskaya A, Shifrin O, Kiryukhin A, Tertychnyy A, Kovalev L, Kovaleva M, Lobanova O, Kudryavtseva A, Krasnov G, Fedorova M, Ivashkin V. Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial. J Clin Med. 2023 Sep 20;12(18):6064. doi: 10.3390/jcm12186064. PMID: 37763004; PMCID: PMC10531936.

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Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota

Roman Maslennikov, Aliya Alieva, Elena Poluektova, Yury Zharikov, Andrey Suslov, Yana Letyagina, Ekaterina Vasileva, Anna Levshina, Evgenii Kozlov, Vladimir Ivashkin

World Journal of Gastroenterology 

DOI: 10.3748/wjg.v29.i27.4236

Abstract

Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased 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 myostatin. These factors have complex negative effects on muscle mass and function. Drug 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 SIBO. However, 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 cirrhosis. No 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.

Keywords: Cirrhosis; Fragility; Liver; Microbiome; Microbiota; Muscle.

Differences in Fecal Short-Chain Fatty Acids between Alcoholic Fatty Liver-Induced Cirrhosis and Non-alcoholic (Metabolic-Associated) Fatty Liver-Induced Cirrhosis

Xinlu Cao, Oksana Zolnikova, Roman Maslennikov, Maria Reshetova, Elena Poluektova, Arina Bogacheva, Maria Zharkova, Vladimir Ivashkin

Metabolites 

DOI: 10.3390/metabo13070859

Abstract

The objective of this study was to investigate the metabolic activity of the gut microbiota in cirrhosis due to different variants of fatty liver disease (alcoholic vs. non-alcoholic [metabolic-associated] one [AFLD and MAFLD]). The present study included 24 patients with alcoholic liver cirrhosis, 16 patients with MAFLD-related cirrhosis, and 20 healthy controls. The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas-liquid chromatography. All patients with cirrhosis showed a decrease in the total content of SCFAs (p < 0.001) and absolute content of acetate (p < 0.001), propionate (p < 0.001), butyrate (p < 0.001), and isovalerate (p < 0.001). In MAFLD cirrhosis, the metabolic activity of the microbiota was significantly altered compared to patients with alcoholic cirrhosis, as evidenced by a lower total SCFA content (p < 0.001) and absolute content of acetate (p < 0.001), propionate (p < 0.001), and butyrate (p < 0.001); a higher relative content of isovalerate (p < 0.001); and a higher IsoCn/Cn ratio (p < 0.001). Various clinical and laboratory parameters correlate differently with fecal SCFAs and their fractions in cirrhosis due to AFLD and MAFLD. SCFA-producing metabolic activity is reduced more in MAFLD cirrhosis than in alcoholic cirrhosis. According to the etiological factors of cirrhosis, disorders of this metabolic activity may be involved in different pathogenetic pathways.

Keywords: gut microbiota; gut–liver axis; liver cirrhosis; short-chain fatty acids.

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Epidemiology of small intestinal bacterial overgrowth

Irina Efremova, Roman Maslennikov, Elena Poluektova, Ekaterina Vasilieva, Yury Zharikov, Andrey Suslov, Yana Letyagina, Evgenii Kozlov, Anna Levshina, Vladimir Ivashkin

World Journal of Gastroenterology 

DOI: 10.3748/wjg.v29.i22.3400

Abstract

Small intestinal bacterial overgrowth (SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The 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 anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicates the course of a number of diseases and may be of pathogenetic significance in the development of their symptoms. SIBO 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 diseases. The development of SIBO is often associated with a slowdown in orocecal transit time that decreases the normal clearance of bacteria from the small intestine. The 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 hormones. In a number of diseases, including cirrhosis, MAFLD, diabetes, and pancreatitis, an association was found between disease severity and the presence of SIBO. Further work on the effect of SIBO eradication on the condition and prognosis of patients with various diseases is required.

Keywords: Breath test; Gut microbiota; Gut-liver axis; Hydrogen; Lactulose; Methane.

For citation: Efremova I, Maslennikov R, Poluektova E, Vasilieva E, Zharikov Y, Suslov A, Letyagina Y, Kozlov E, Levshina A, Ivashkin V. Epidemiology of small intestinal bacterial overgrowth. World J Gastroenterol. 2023 Jun 14;29(22):3400-3421. doi: 10.3748/wjg.v29.i22.3400. PMID: 37389240; PMCID: PMC10303511.

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Small Intestinal Bacterial Overgrowth Is Associated with Poor Prognosis in Cirrhosis

Irina Efremova, Roman Maslennikov, Aliya Alieva, Elena Poluektova, Vladimir Ivashkin

Microorganisms 

DOI: 10.3390/microorganisms11041017

Abstract

Background: Small intestinal bacterial overgrowth (SIBO) is associated with numerous manifestations of cirrhosis. To determine whether the presence of SIBO affects the prognosis in cirrhosis was the aim of the study.

Methods: This prospective cohort study included 50 patients. All participants underwent a lactulose hydrogen breath test for SIBO. The follow-up period was 4 years.

Results: SIBO was detected in 26 (52.0%) patients: in 10 (52.6%) patients with compensated cirrhosis and in 16 (51.6%) ones with decompensated cirrhosis. Twelve (46.2%) patients with SIBO and four (16.7%) patients without SIBO died within 4 years (p = 0.009). Among patients with decompensated cirrhosis, 8 (50.0%) patients with SIBO and 3 (20.0%) patients without SIBO died (p = 0.027). Among patients with compensated cirrhosis, four (40.0%) patients with SIBO and one (11.1%) patient without SIBO died (p = 0.045). Among patients with SIBO, there was no difference in mortality between patients with compensated and decompensated cirrhosis (p = 0.209). It was the same for patients without SIBO (p = 0.215). SIBO affects the prognosis only in the first year of follow-up in decompensated cirrhosis, and only in subsequent years in compensated cirrhosis. Presence of SIBO (p = 0.028; HR = 4.2(1.2-14.9)) and serum albumin level (p = 0.027) were significant independent risk factors for death in cirrhosis.

Conclusions: SIBO is associated with poor prognosis in cirrhosis.

Keywords: SIBO; bacterial translocation; gut microbiome; gut microbiota; prognosis.

For citation: Efremova I, Maslennikov R, Alieva A, Poluektova E, Ivashkin V. Small Intestinal Bacterial Overgrowth Is Associated with Poor Prognosis in Cirrhosis. Microorganisms. 2023 Apr 13;11(4):1017. doi: 10.3390/microorganisms11041017. PMID: 37110440; PMCID: PMC10143588.

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Ksenia Dmitrieva, Roman Maslennikov, Ekaterina Vasilieva, Salekh Aliev, Vyacheslav Bakhitov, Vadim Marcinkevich, Anna Levshina, Evgenii Kozlov, Vladimir Ivashkin, Elena Poluektova

Journal of Infection and Public Health

DOI: 10.1016/j.jiph.2023.04.008

Abstract

Objectives: The aim is to study impact of vaccination against the novel coronavirus disease (COVID-19) with Sputnik V on mortality during the period of predominance of the delta variant of SARS-CoV-2.

Methods: This was a retrospective cohort study of individuals with state health insurance at the Moscow Ambulatory Center. The cohorts included 41,444 persons vaccinated with Sputnik V, 15,566 survivors of COVID-19, and 71,377 non-immune persons. The deaths of patients that occurred from June 1, 2021, to August 31, 2021, were analyzed.

Results: Overall (0.39 % vs. 1.92 %; p < 0.001), COVID-19-related (0.06 % vs. 0.83 %; p < 0.001), and non-COVID mortality (0.33 % vs. 1.09 %; p < 0.001) was lower among vaccinated individuals than among non-immune individuals. The efficacy of vaccination against death from COVID-19 was 96 % [95 % CI 91-98 %] in the general population, 100 % among those aged 18-50 years, 97 % [95 % CI 76-100 %] among those aged 51-70 years, 98 % [95 % CI 90-100 %] among those aged 71-85 years, and 88 % [95 % CI 49-97 %] among those aged > 85 years.

Conclusion: COVID-19 vaccination with Sputnik V is associated with a decrease in overall and COVID-19-related mortality and is not with increased non-COVID mortality.

Keywords: Gam-COVID-Vac; Mortality; SARS-CoV-2; Safety; Vaccine.

For citation: Dmitrieva K, Maslennikov R, Vasilieva E, Aliev S, Bakhitov V, Marcinkevich V, Levshina A, Kozlov E, Ivashkin V, Poluektova E. Impact of vaccination against the novel coronavirus infection (COVID-19) with Sputnik V on mortality during the delta variant surge. J Infect Public Health. 2023 Jun;16(6):922-927. doi: 10.1016/j.jiph.2023.04.008. Epub 2023 Apr 13. PMID: 37086551; PMCID: PMC10098368.

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Vladimir Ivashkin, Oleg Shifrin, Roman Maslennikov, Elena Poluektova, Alexander Korolev, Anna Kudryavtseva, George Krasnov, Nona Benuni, Giovanni Barbara

BMC Gastroenterology 

DOI: 10.1186/s12876-023-02690-x

Abstract

Background: Rifaximin effectively treats symptomatic uncomplicated diverticular disease (SUDD) and has shown eubiotic potential (i.e., an increase in resident microbial elements with potential beneficial effects) in other diseases. This study investigated changes in the fecal microbiome of patients with SUDD after repeated monthly treatment with rifaximin and the association of these changes with the severity of abdominal pain.

Methods: This was a single-center, prospective, observational, uncontrolled cohort study. Patients received rifaximin 400 mg twice a day for 7 days per month for 6 months. Abdominal pain (assessed on a 4-point scale from 0 [no pain] to 3 [severe pain]) and fecal microbiome (assessed using 16 S rRNA gene sequencing) were assessed at inclusion (baseline) and 3 and 6 months. The Spearman's rank test analyzed the relationship between changes in the gut microbiome and the severity of abdominal pain. A p-value ≤ 0.05 was considered statistically significant.

Results: Of the 23 patients enrolled, 12 patients completed the study and were included in the analysis. Baseline abdominal pain levels decreased significantly after 3 (p = 0.036) and 6 (p = 0.008) months of treatment with rifaximin. The abundance of Akkermansia in the fecal microbiome was significantly higher at 3 (p = 0.017) and 6 (p = 0.015) months versus baseline. The abundance of Ruminococcaceae (p = 0.034), Veillonellaceae (p = 0.028), and Dialister (p = 0.036) were significantly increased at 6 months versus baseline, whereas Anaerostipes (p = 0.049) was significantly decreased. The severity of abdominal pain was negatively correlated with the abundance of Akkermansia (r=-0.482; p = 0.003) and Ruminococcaceae (r=-0.371; p = 0.026) but not with Veillonellaceae, Dialister, or Anaerostipes. After 3 months of rifaximin, abdominal pain was significantly less in patients with Akkermansia in their fecal microbiome than in patients without Akkermansia (p = 0.022).

Conclusion: The eubiotic effect of rifaximin was associated with decreased abdominal pain in patients with SUDD.

Keywords: Abdominal pain; Akkermansia; Diverticular disease; Eubiotic; Rifaximin.

For citation: Ivashkin V, Shifrin O, Maslennikov R, Poluektova E, Korolev A, Kudryavtseva A, Krasnov G, Benuni N, Barbara G. Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic uncomplicated diverticular disease: results from an observational cohort study. BMC Gastroenterol. 2023 Mar 23;23(1):82. doi: 10.1186/s12876-023-02690-x. PMID: 36959568; PMCID: PMC10037807.

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Low Short-Chain-Fatty-Acid-Producing Activity of the Gut Microbiota Is Associated with Hypercholesterolemia and Liver Fibrosis in Patients with Metabolic-Associated (Non-Alcoholic) Fatty Liver Disease

 Xinlu Cao, Oksana Zolnikova, Roman Maslennikov, Maria Reshetova, Elena Poluektova, Arina Bogacheva, Maria Zharkova, Vladimir Ivashkin

 Gastrointestinal Disorders

 https://doi.org/10.3390/gidisord5040038

Abstract

The aim of this study was to investigate the short-chain fatty acid (SCFA) activity of the gut microbiota of patients with metabolic-associated fatty liver disease (MAFLD). The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas–liquid chromatography. Liver fibrosis was assessed using the FIB-4 index and elastography. Among 42 non-cirrhotic MAFLD patients, 24 had high fecal SCFA levels (group H) and 18 had low fecal SCFA levels (group L). Patients in group H had lower serum uric acid, total cholesterol, and LDL cholesterol levels but a higher BMI than those in group L. All patients in group L and only 37.9% of those in group H were found to have hypercholesterolemia. In patients with hypercholesterolemia, the level of SCFAs was lower than that in patients without hypercholesterolemia. Patients in group H had less liver fibrosis than patients in group L. A total of 50.0% of the patients in group H and 92.3% of those in group L had significant liver fibrosis (≥F2). Patients with significant liver fibrosis had lower levels of fecal SCFAs—particularly acetate and butyrate. The fecal SCFA levels were positively correlated with gamma-glutamyl transferase, total bilirubin levels, BMI, and platelet count and were negatively correlated with FIB-4, liver stiffness, serum total, and LDL cholesterol levels.

Keywords: MAFLD; NAFLD; short-chain fatty acids; gut microbiota; gut–liver axis.

For citation:Cao, X.; Zolnikova, O.; Maslennikov, R.; Reshetova, M.; Poluektova, E.; Bogacheva, A.; Zharkova, M.; Ivashkin, V. Low Short-Chain-Fatty-Acid-Producing Activity of the Gut Microbiota Is Associated with Hypercholesterolemia and Liver Fibrosis in Patients with Metabolic-Associated (Non-Alcoholic) Fatty Liver Disease. Gastrointest. Disord. 2023, 5, 464-473. https://doi.org/10.3390/gidisord5040038

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Structure and Metabolic Activity of the Gut Microbiota in Diarrhea-Predominant Irritable Bowel Syndrome Combined with Functional Dyspepsia

Aleksandra Kovaleva, Elena Poluektova, Roman Maslennikov, Oxana Zolnikova, Oleg Shifrin, Anna Kudryavtseva, George Krasnov, Maria Fedorova, Anna Karchevskaya, Vladimir Ivashkin

Gastrointestinal Disorders

 https://doi.org/10.3390/gidisord5030024

 Abstract

Gut dysbiosis presents in many digestive diseases. The aim of this study is to investigate the composition of the gut microbiota and its metabolic activity in patients with diarrhea-predominant irritable bowel syndrome combined with functional dyspepsia (I + D). This study included 60 patients with I + D and 20 healthy controls. Gut microbiota composition was studied using 16S rRNA gene sequencing. The short-chain fatty acids (SCFAs) spectrum was determined via gas–liquid chromatography. Patients with I + D had an increase in the abundance of Holdemanella, Erysipelotrichaceae, Erysipelotrichales, Prevotellaceae, Agathobacter, Slackia, Lactococcus, Pseudomonadaceae, Stenotrophomonas, Xanthomonadaceae, Rhizobiaceae, Erysipelatoclostridiaceae, Lachnospiraceae, and other taxa in addition to a decrease in the abundance of Frisingicoccus, Ralstonia, Burkholderiaceae, Hungatella, Eisenbergiella, Parabacteroides, Peptostreptococcaceae, Merdibacter, Bilophila, Rikenellaceae, Tannerellaceae, Bacteroidaceae, and Flavonifractor in comparison to controls. Patients with I + D showed significantly higher total SCFA content in feces; increased absolute content of acetic acid, propionic acid, butyric acid, and isoacids; and a significant negative shift in the anaerobic index. The relative levels of the main SCFAs and isoacids in the patient group did not differ significantly from those in the control group. The fecal acetate and isoacid levels correlated with the severity of diarrhea. The fecal butyrate level correlated with the severity of flatulence.

Keywords: irritable bowel syndrome; functional dyspepsia; short-chain fatty acids; gut microbiota; gut microbiome

For citation:Kovaleva, A.; Poluektova, E.; Maslennikov, R.; Zolnikova, O.; Shifrin, O.; Kudryavtseva, A.; Krasnov, G.; Fedorova, M.; Karchevskaya, A.; Ivashkin, V. Structure and Metabolic Activity of the Gut Microbiota in Diarrhea-Predominant Irritable Bowel Syndrome Combined with Functional Dyspepsia. Gastrointest. Disord. 2023, 5, 296-309. https://doi.org/10.3390/gidisord5030024

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Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis

Roman Maslennikov, Elena Poluektova, Oxana Zolnikova, Alla Sedova, Anastasia Kurbatova, Yulia Shulpekova, Natyia Dzhakhaya, Svetlana Kardasheva, Maria Nadinskaia, Elena Bueverova, Vladimir Nechaev, Anna Karchevskaya, Vladimir Ivashkin

 International Journal of Molecular Sciences

 https://doi.org/10.3390/ijms242216502

 Abstract

Cirrhosis is the end result of liver fibrosis in chronic liver diseases. Studying the mechanisms of its development and developing measures to slow down and regress it based on this knowledge seem to be important tasks for medicine. Currently, disorders of the gut–liver axis have great importance in the pathogenesis of cirrhosis. However, gut dysbiosis, which manifests as increased proportions in the gut microbiota of Bacilli and Proteobacteria that are capable of bacterial translocation and a decreased proportion of Clostridia that strengthen the intestinal barrier, occurs even at the pre-cirrhotic stage of chronic liver disease. This leads to the development of bacterial translocation, a process by which those microbes enter the blood of the portal vein and then the liver tissue, where they activate Kupffer cells through Toll-like receptor 4. In response, the Kupffer cells produce profibrogenic cytokines, which activate hepatic stellate cells, stimulating their transformation into myofibroblasts that produce collagen and other elements of the extracellular matrix. Blocking bacterial translocation with antibiotics, probiotics, synbiotics, and other methods could slow down the progression of liver fibrosis. This was shown in a number of animal models but requires further verification in long-term randomized controlled trials with humans.

Keywords: gut–liver axis; gut microbiota; endotoxemia; gut microbiome; cirrhosis; fibrosis; hepatitis

For citations: Maslennikov, R.; Poluektova, E.; Zolnikova, O.; Sedova, A.; Kurbatova, A.; Shulpekova, Y.; Dzhakhaya, N.; Kardasheva, S.; Nadinskaia, M.; Bueverova, E.; et al. Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis. Int. J. Mol. Sci. 2023, 24, 16502. https://doi.org/10.3390/ijms242216502

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A metabolic activity recovery of intestinal microbiota in the patients with bronchial asthma

Ozimek M., Ivashkin V., Zolnikova O., Potskherashvili N.,  Ivashkin K., Dzhakhaya N., Kurbatova A., Kryuchkova K., Zaborova V

Pulmonary Medicine

https://doi.org/10.1155/2022/9902438

Abstract

Goals. We assessed the possibilities of correcting the short-chain fatty acids (SCFA) content and profiles in feces of patients with bronchial asthma. Background. It was established that the high biological diversity of intestinal microorganisms promotes the needed SCFAs production, which induces immune regulatory pathways and contributes to the anti-inflammatory response. Study. A group of 30 patients with allergic bronchial asthma (BA) were investigated in our study. All of the patients were tested for the presence of SIBO by the SCFA spectrum determination. For the SIBO treatment, 10 patients from the studied group were prescribed Rifaximinum with the 200 mg dose at 3 times a day for a week; the other 10 patients were prescribed Rifaximinum at the same dose, followed by the administration of the Lactobalance probiotic in capsules at 3 times a day for a month. A month probiotic course was assigned to the remaining 10 patients without SIBO, as part of the BA complex therapy. The SCFA studies were immediately carried out for all of the patients after the 1 month probiotic therapy course. Results. A normalization of the SCFA spectrum and anaerobic index for all of the studied patients were noted. Upon taking the probiotics, it was revealed in the patients without SIBO that the total content of fatty acids (p<0,001), acetic and butyric acid (p<0,001) had increased. The Rifaximinum course, followed by administration of the probiotics led to a decrease of the relative amount of isoacids and ratio of isoacids/acids in the studied patients as compared to the patients who had received Rifaximinum for the SIBO treatment only (p<0,05). Conclusion. The obtained results demonstrate a potential opportunity of the drug influence on the active bacterial metabolites composition and amount in the intestinal biotope; as it was confirmed by the restoration of the intestinal microbiocenosis and microorganism habitat.

For citation: Ozimek M, Ivashkin V, Zolnikova O, Potskherashvili N, Ivashkin K, Dzhakhaya N, Kurbatova A, Kryuchkova K, Zaborova V. A Metabolic Activity Recovery of the Intestinal Microbiota in the Patients with Bronchial Asthma. Pulm Med. 2022 Sep 19;2022:9902438. doi: 10.1155/2022/9902438. PMID: 36247882; PMCID: PMC9553837.

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Efficacy and safety of a food supplement with standardized menthol, limonene, and gingerol content in patients with irritable bowel syndrome: A double-blind, randomized, placebo-controlled trial

Vladimir Ivashkin, Anna Kudryavtseva, George Krasnov,Yuri Poluektov, Margarita Morozova, Oleg Shifrin, Allan Beniashvili, Zarina Mamieva, Alexandra Kovaleva, Anatoly Ulyanin,  Elizaveta Trush, Alexander Erlykin

PLoS ONE

https://doi.org/10.1371/journal.pone.0263880

Abstract

Background. Irritable bowel syndrome (IBS) affects 9,2% of the global population and places a considerable burden on healthcare systems. Most medications for treating IBS, including spasmolytics, laxatives, and antidiarrheals, have low efficacy. Effective and safe therapeutic treatments have yet to be developed for IBS.

Purpose. This study assessed the efficacy and safety of a food supplement containing standardized menthol, limonene, and gingerol in human participants with IBS or IBS/functional dyspepsia (FD).

Design. A double-blind, randomized, placebo-controlled trial.

Methods. We randomly assigned 56 patients with IBS or IBS/FD to an intervention group (Group 1) or control group (Group 2) that were given supplement or placebo, respectively, in addition to the standard treatment regimen for 30 d. Three outpatient visits were conducted during the study. Symptom severity was measured at each visit using a 7×7 questionnaire. Qualitative and quantitative composition of the intestinal microbiota were assessed at visits 1 and 3 based on 16S rRNA gene sequencing.

Results. At visit 1 (before treatment), the median total 7×7 questionnaire score was in the moderately ill range for both groups, with no difference between the groups (p = 0.1). At visit 2, the total 7×7 score decreased to mildly ill, with no difference between the groups (p = 0.4). At visit 3, the total score for group 1 indicated borderline illness and for group 2 remained indicated mild illness (p = 0.009). Even though we observed some variations in gut microbiota between the groups, we did not find any statistically significant changes.

Conclusion. The food supplement with standardized menthol, limonene, and gingerol content increased the efficacy of standard therapy in IBS and FD patients. The use of the supplement did not cause any obvious side effects.

For citation: Ivashkin VT, Kudryavtseva AV, Krasnov GS, Poluektov YM, Morozova MA, Shifrin OS, Beniashvili AG, Mamieva ZA, Kovaleva AL, Ulyanin AI, Trush EA, Erlykin AG, Poluektova EA. Efficacy and safety of a food supplement with standardized menthol, limonene, and gingerol content in patients with irritable bowel syndrome: A double-blind, randomized, placebo-controlled trial. PLoS One. 2022 Jun 15;17(6):e0263880. doi: 10.1371/journal.pone.0263880. PMID: 35704960; PMCID: PMC9200470.

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Clostridioides difficile co-infection in patients with COVID-19

Roman Maslennikov, Vladimir Ivashkin, Anna Ufimtseva, Elena Poluektova, Anatoly Ulyanin

Future Microbiology

https://doi.org/10.2217/fmb-2021-0145

Abstract

Aim: To assess the impact of Clostridioides difficile infection on the course of COVID-19. Methods: The authors included 809 patients with COVID-19 in this retrospective study: 55 had C. difficile infection, 23 had C. difficile-negative antibiotic-associated diarrhea and 731 had no diarrhea. C. difficile in feces was determined by immunochromatographic test for its toxins. Results:C. difficile infection was associated with increased risk of death (hazard ratio = 2.6; p = 0.021), especially after 20 days of disease (hazard ratio = 6.5; p < 0.001). C. difficile infection-associated diarrhea was longer and more severe than C. difficile-negative antibiotic-associated diarrhea. Unlike patients with C. difficile-negative antibiotic-associated diarrhea, patients with C. difficile infection were admitted to the intensive care unit and needed mechanical ventilation more often than those without diarrhea. Conclusion:C. difficile infection worsens the course and prognosis of COVID-19.

Keywords: COVID-19; Clostridioides difficile; Clostridium difficile; SARS-CoV-2; antibiotic-associated diarrhea; coronavirus.

For citation: Maslennikov R, Ivashkin V, Ufimtseva A, Poluektova E, Ulyanin A. Clostridioides difficile co-infection in patients with COVID-19. Future Microbiol. 2022 Jun;17:653-663. doi: 10.2217/fmb-2021-0145. Epub 2022 Apr 20. PMID: 35440149; PMCID: PMC9020461.

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

Zarina Mamieva, Elena Poluektova,  Valery Svistushkin,   Vasily Sobolev,   Oleg Shifrin,  Francisco Guarner, Vladimir Ivashkin

World Journal of Gastroenterology

doi: 10.3748/wjg.v28.i12.1204

Abstract

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 distension. IBS 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 systems. Despite extensive research, the etiology and underlying pathophysiology of IBS remain incompletely understood. Proposed mechanisms involved in its pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, and emotional disorders. Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis. The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota. Moreover, antibiotics have been suggested to play a role in the development of IBS. Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS. This suggestion is further supported by data from cohort and case-control studies, indicating that antibiotic treatment is associated with an increased risk of IBS. This 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.

Keywords: Antibiotics; Gut microbiota; Gut motility; Gut sensitivity; Intestinal barrier; Irritable bowel syndrome.

For citation: Mamieva Z, Poluektova E, Svistushkin V, Sobolev V, Shifrin O, Guarner F, Ivashkin V. Antibiotics, gut microbiota, and irritable bowel syndrome: What are the relations? World J Gastroenterol. 2022 Mar 28;28(12):1204-1219. doi: 10.3748/wjg.v28.i12.1204. PMID: 35431513; PMCID: PMC8968486.

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

Roman Maslennikov, Vladimir Ivashkin, Irina Efremova, Elena Poluektova, Anna Kudryavtseva, George  Krasnov

World Journal of Gastroenterology

doi: 10.3748/wjg.v28.i10.1067

Abstract

Background: Gut dysbiosis and small intestinal bacterial overgrowth (SIBO) are commonly observed in patients with cirrhosis. Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis, dysbiosis and SIBO were always studied separately.

Aim: To study the relationship of gut dysbiosis and SIBO in cirrhosis.

Methods: This observational study included 47 in-patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. SIBO was assessed using the lactulose hydrogen breath test.

Results: SIBO was found in 24/47 (51.1%) patients. Patients 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 SIBO. This 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 SIBO. Reduced 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 SIBO.

Conclusion: Despite the differences observed in the gut microbiome between patients with and without SIBO, gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.

Keywords: Cirrhosis; Dysbiosis; Gut-liver axis; Microbiome; Microbiota; Small intestinal bacterial overgrowth.

For citation: Maslennikov R, Ivashkin V, Efremova I, Poluektova E, Kudryavtseva A, Krasnov G. Gut dysbiosis and small intestinal bacterial overgrowth as independent forms of gut microbiota disorders in cirrhosis. World J Gastroenterol. 2022 Mar 14;28(10):1067-1077. doi: 10.3748/wjg.v28.i10.1067. PMID: 35431497; PMCID: PMC8968519.

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Gut dysbiosis and body composition in cirrhosis

Roman Maslennikov, Vladimir Ivashkin,  Aliya Alieva, Elena Poluektova, Anna Kudryavtseva,  George Krasnov,  Maria Zharkova, Yuri Zharikov

World Journal of Hepatology

doi: 10.4254/wjh.v14.i6.1210

Abstract

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 cirrhosis.

Aim: To study the relationship between the gut microbiota and body composition in cirrhosis.

Methods: This observational study included 46 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Multifrequency bioelectrical impedance analysis was performed to assess body composition in these patients.

Results: 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, respectively. Changes in the gut microbiome were not independently associated with the fat mass percentage in cirrhosis. The 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 deficiency. The amount of extracellular fluid increased in 22/46 (47.6%) patients. Proteobacteria 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 patients. Patients 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..

Keywords: Cirrhosis; Dysbiosis; Gut-Liver axis; Malnutrition; Microbiome; Microbiota; Sarcopenia.

For citation: Maslennikov R, Ivashkin V, Alieva A, Poluektova E, Kudryavtseva A, Krasnov G, Zharkova M, Zharikov Y. Gut dysbiosis and body composition in cirrhosis. World J Hepatol. 2022 Jun 27;14(6):1210-1225. doi: 10.4254/wjh.v14.i6.1210. PMID: 35978666; PMCID: PMC9258262.

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

Roman Maslennikov, Irina Efremova, Vladimir Ivashkin, Maria Zharkova, Elena Poluektova,  Elena Shirokova,  Konstantin Ivashkin

World Journal of Hepatology

doi: 10.4254/wjh.v14.i8.1667

Abstract

Background: Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease course. Probiotics may reduce bacterial translocation and may therefore be useful to redress the circulatory imbalance.

Aim: To investigate the effect of probiotics on hemodynamic parameters, systemic inflammation, and complications of cirrhosis in this randomized placebo-controlled trial.

Methods: 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 period. Liver function and the systemic hemodynamic status were evaluated pre- and post-intervention. Echocardiography and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic indicators. Cardiac output and systemic vascular resistance were calculated.

Results: 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.

Keywords: Gut; Gut-heart axis; Gut-liver axis; Heart; Hemodynamics; Microbiota; Portal hypertension; Saccharomyces boulardii.

For citation: Maslennikov R, Efremova I, Ivashkin V, Zharkova M, Poluektova E, Shirokova E, Ivashkin K. Effect of probiotics on hemodynamic changes and complications associated with cirrhosis: A pilot randomized controlled trial. World J Hepatol. 2022 Aug 27;14(8):1667-1677. doi: 10.4254/wjh.v14.i8.1667. PMID: 36157871; PMCID: PMC9453455.

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Direct and Indirect Methods for Studying Human Gut Microbiota

Vladimir Ivashkin, Oleg Medvedev, Elena Poluektova, Anna Kudryavtseva, Ildar Bakhtogarimov, Anna Karchevskaya

Russian Journal of Gastroenterology, Hepatology, Coloproctology

https://doi.org/10.22416/1382-4376-2022-32-2-19-34

Abstract

Aim: To review the main methods of intestinal microbiota studying.

Key  points.  Currently,  molecular  genetic  methods  are  used  mainly  for  basic  research  and  do  not  have  a  unified  protocol for data analysis, which makes it difficult to implement them in clinical practice. Measurement of short chain fatty acids (SCFA) concentrations in plasma provides the data, which can serve as an indirect biomarker of the colonic microbiota  composition.  However,  currently  available  evidence  is  insufficient  to  relate  the  obtained  values  (SCFA  levels and ratio) to a particular disease with a high degree of certainty. Trimethylamine N-oxide (TMAO) levels in the blood plasma and urine can also reflect the presence of specific bacterial clusters containing genes Cut, CntA/CntB and YeaW/YeaX. Therefore, further studies are required to reveal possible correlations between certain disorders and such parameters as the composition of gut microbiota, dietary patterns and TMAO concentration. Gas biomarkers, i.e.  hydrogen,  methane  and  hydrogen  sulphide,  have  been  studied  in  more  detail  and  are  better  understood  as  compared  to  other  biomarkers  of  the  gut  microbiome  composition  and  functionality.  The  main  advantage  of  gas  biomarkers  is  that  they  can  be  measured  multiple  times  using  non-invasive  techniques.  These  measurements  provide  information  on  the  relative  proportion  of  hydrogenic  (i.e.  hydrogen  producing)  and  hydrogenotrophic  (i.e.  methanogenic  and  sulfate-reducing)  microorganisms.  In  its  turn,  this  opens  up  the  possibility  of  developing  new  approaches to correction of individual microbiota components. Conclusions.  Integration  of  the  data  obtained  by  gut  microbiota  studies  at  the  genome,  transcriptome  and  metabolome  levels  would  allow  a  comprehensive  analysis  of  microbial  community  function  and  its  interaction  with  the human organism. This approach may increase our understanding of the pathogenesis of various diseases as well open up new opportunities for prevention and treatment.

Keywords: microbiota, microbiome, metabolome, transcriptome, sequencing, trimethylamine, trimethylaminoxide, short-chain fatty acids, hydrogen, methane, hydrogen sulfide

For citation: Ivashkin  V.T.,  Medvedev  O.S.,  Poluektova  E.A.,  Kudryavtseva  A.V.,  Bakhtogarimov  I.R.,  Karchevskaya  A.E.  Direct  and  Indirect  Methods  for  Studying  Human  Gut  Microbiota.  Russian  Journal  of  Gastroenterology,  Hepatology,  Coloproctology.  2022;32(2):19–34. https://doi.org/10.22416/1382-4376-2022-32-2-19-34 

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Determination of Probiotics Prescription Indications in Patients with Irritable Bowel Syndrome (Materials of the Expert Council and Literature Review)

Vladimir Ivashkin, Igor Mayev, Olga Alekseeva, Sergey Alekseenko, Natalia Korochanskaya, Elena Poluektova, Vladimir Simanenkov, Alexander Trukhmanov, Igor Khlynov, Vladislav Tsukanov, Oleg Shifrin, Tatiana Lapina, Roman Maslennikov, Anatoly Ulyanin.

Russian Journal of Gastroenterology, Hepatology, Coloproctology

https://doi.org/10.22416/1382-4376-2022-32-2-9-18

Abstract

Aim. To review the main indications for probiotics prescription in patients with irritable bowel syndrome and to present the materials of an Expert Council, which was held on 18 March 2022 in Moscow.

Key points. Gut microbiota disturbance is an integral part of irritable bowel syndrome (IBS) pathogenesis. Changes of colonic microbiota composition are associated with its functional potential modification, which leads to an increasing of the pro-inflammatory immune response, as well as to an exacerbation of the disease symptoms and quality of life decreasing in patients with IBS. The novel coronavirus infection (COVID-19) is an independent risk factor for both exacerbation and onset of IBS, which predispose to increase IBS incidence. Correction of gut microbiota composition with probiotics seems to be a promising therapeutic target for IBS treatment optimizing. The optimal probiotic should  be  effective,  safe,  strain-specific,  and  its  dose  and  duration  of  administration  should  be  confirmed  by  the  results of clinical studies. Some of the probiotics with proven efficacy in IBS are Alflorex® and Enterol®.

Conclusion.  Prescription  of  certain  probiotics  in  IBS  is  advisable  to  normalize  the  frequency  and  consistency  of  stools, relieve abdominal pain and bloating, as well as improve patients’ quality of life.

Keywords:  irritable  bowel  syndrome,  novel  coronavirus  infection,  COVID-19,  probiotics,  Bifidobacterium  longum 35624, Alflorex®, Saccharomyces boulardii CNCM I-745, Enterol®Keywords: microbiota, microbiome, metabolome, transcriptome, sequencing, trimethylamine, trimethylaminoxide, short-chain fatty acids, hydrogen, methane, hydrogen sulfide

For citation: Ivashkin V.T., Mayev I.V., Alekseeva O.P., Alekseenko S.A., Korochanskaya N.V., Poluektova E.A., Simanenkov V.I., Trukhmanov A.S., Khlynov I.B., Tsukanov V.V., Shifrin O.S., Lapina T.L., Maslennikov R.V., Ulyanin A.I. Determination of Probiotics Prescription Indications in Patients with Irritable Bowel Syndrome (Materials of the Expert Council and Literature Review). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(2):9–18. https://doi.org/10.22416/1382-4376-2022-32-2-9-18

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Metabolomic profiles as a new understanding of disease processes

Oxana Zolnikova, Maria  Reshetova, Marina  Ivanova, Vladimir Ivashkin.

Russian Journal of Gastroenterology, Hepatology, Coloproctology

https://doi.org/10.22416/1382-4376-2022-32-2-9-18

Abstract

Aim. This review will demonstrate possibilities of using metabolomic profiling to identify biomarkers of various inter-nal organs diseases.

Key points. A new diagnostic direction is associated with high-sensitive spectral analysis of biomarker molecules. This review will discuss some of the latest advances with an emphasis on the use of metabolomics to identify major metabolic  changes  in  various  diseases.  The  possibility  of  finding  diagnostic  markers  in  diseases  of  the  gastroin-testinal tract, respiratory and cardiovascular systems, in oncology, endocrinology, neurology are discussed. These results define new potential therapeutic strategies, making metabolomics useful for a wide range of biomedical and pharmaceutical research.

Conclusion.  Metabolomic  profile  changes  in  different  types  of  diseases  will  help  to  improve  understanding  of  the pathogenesis. New therapeutic approaches may be developed. They will take into account individual characteristics of the patient, identified by using current molecular technologies. The results of metabolomic studies can be used to monitor treatment outcomes.

Keywords: metabolites, metabolomic profiling, biomarkers, mass spectrometry, liquid chromatography, treatment monitoring

For citation: Zolnikova O.Yu., Reshetova M.S., Ivanova M.N., Ivashkin V.T. Metabolomic profiles as a new understanding of disease processes. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(1):46–52. https://doi.org/10.22416/1382-4376-2022-32-1-46-52

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Guideline of the Scientific Community for Human Microbiome Research (CHMR) and the Russian Gastroenterological Association (RGA) on Small Intestinal Bacterial Overgrowth in Adults

Vladimir Ivashkin, Igor Maev, Diana Abdulganieva, Olga Alekseeva, Sergey Alekseenko, Oxana Zolnikova, Natalia Korochanskaya, Oleg Medvedev, Elena Poluektova, Vladimir  Simanenkov, Alexander Trukhmanov, Igor  Khlynov, Vladislav Tsukanov, Oleg Shifrin, Konstantin VIvashkin, Tatiana Lapina, Roman  Maslennikov, Maria Fadeeva, Anatoly Ulyanin

Russian Journal of Gastroenterology, Hepatology, Coloproctology

https://doi.org/10.22416/1382-4376-2022-32-3-68-85

Abstract

Aim. To optimize the choice of treatment strategies by physicians and gastroenterologists to improve treatment and prevention of small intestinal bacterial overgrowth (SIBO) in adults.

Key points. SIBO is a condition characterized by an increased amount and/or abnormal composition of the microbiota in the small intestine. Clinically, the syndrome is manifested by nonspecific gastroenterological complaints and the development of malabsorption syndrome. Most often, SIBO is associated with various chronic non- infectious diseases (both diseases of the gastrointestinal tract, and the cardiovascular system and the neuromuscular apparatus) and can affect the severity of their symptoms. Specific methods for diagnosing SIBO are the culture method and breath tests. The main approaches to the treatment of SIBO include the elimination of the underlying cause of its occurrence, the use of antibacterial drugs and adherence to dietary recommendations (elemental diet).

Conclusion. Small intestinal bacterial overgrowth is common in patients with various diseases, but has non-specific manifestations, so proper diagnosis of this condition is required. SIBO therapy involves prescription of antibacterial agents, the most studied of which is the non-absorbable antibiotic rifaximin-α.

Keywords: small intestinal bacterial overgrowth, microbiota, breath testing, rifaximin-α

For citation: Ivashkin V.T., Maev I.V., Abdulganieva D.I., Alekseeva O.P., Alekseenko S.A., Zolnikova O.Yu., Korochanskaya N.V., Medvedev O.S., Poluektova E.A., Simanenkov V.I., Trukhmanov A.S., Khlynov I.B., Tsukanov V.V., Shifrin O.S., Ivashkin K.V., Lapina T.L., Maslennikov R.V., Fadeeva M.V., Ulyanin A.I. Practical Recommendation of the Scientific Сommunity for Human Microbiome Research (CHMR) and the Russian Gastroenterological Association (RGA) on Small Intestinal Bacterial Overgrowth in Adults. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(3):68-85. https://doi.org/10.22416/1382-4376-2022-32-3-68-85

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

Roman Maslennikov, Vladimir Ivashkin, Irina Efremova, Elena Poluektova, Elena Shirokova

World Journal of Clinical Cases

doi: 10.12998/wjcc.v9.i31.9320 

Abstract

Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease, especially cirrhosis. This introduces the concept of the gut-liver axis, which can be imagined as a chain connected by several links. Gut dysbiosis, small intestinal bacterial overgrowth, and intestinal barrier alteration lead to bacterial translocation, resulting in systemic inflammation. 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 prognosis. The 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 cirrhosis. However, 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 studied. They remain a missing link in the gut-liver axis and a challenge for future research.

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

For citation: Maslennikov R, Ivashkin V, Efremova I, Poluektova E, Shirokova E. Gut-liver axis in cirrhosis: Are hemodynamic changes a missing link? World J Clin Cases. 2021 Nov 6;9(31):9320-9332. doi: 10.12998/wjcc.v9.i31.9320. PMID: 34877269; PMCID: PMC8610853.

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Two consecutive attacks of diarrhea in 15 COVID-19 patients: An antibiotic-associated one following the viral one

Roman Maslennikov, Vladimir Ivashkin, Anna Ufimtseva, Elena Poluektova

Revista de Gastroenterologia de Mexico

https://doi.org/10.1016/j.rgmx.2021.06.007

Abstract

Of the 971 patients admitted to our Clinic with suspected COVID-19, 15 (1.5%) presented with two consecutive attacks of diarrhea. One of those patients (a 47-year-old woman) required admission to the intensive care unit and mechanical ventilation. She died on the 11th day of hospitalization (18th day of illness). The first attack of diarrhea in those patients occurred on the 6 th (4th-7th) day of disease and lasted 3 (3-5) days. The second attack of diarrhea developed 11 (8-12) days after the initial onset of diarrhea. Despite the existing trend, the difference in the duration of the diarrhea and the maximum number of bowel movements per day between the first and second attacks was not statistically significant (p = 0.130; p = 0.328). There was no significant difference between the patients with a double attack of diarrhea and those with no diarrhea, regarding the results of the complete blood count, biochemical blood tests, and inflammation biomarkers.

Keywords: COVID-19; Diarrhea.

For citation: Maslennikov R, Ivashkin V, Ufimtseva A, Poluektova E. Dos ataques de diarrea consecutivos en 15 pacientes de COVID-19: uno asociado con antibióticos posterior a uno viral [Two consecutive attacks of diarrhea in 15 COVID-19 patients: An antibiotic-associated one following the viral one]. Rev Gastroenterol Mex. 2022 Jan-Mar;87(1):59-62. Spanish. doi: 10.1016/j.rgmx.2021.06.007. Epub 2021 Nov 5. PMID: 34754133; PMCID: PMC8570403.

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Irritable Bowel and Bacterial Overgrowth Syndromes: a Bacterial Link Hypothesis of Functional Disease

Konstantin Ivashkin, Vasilisa Grechishnikova, Maria Reshetova, Vladimir Ivashkin

Russian Journal of Gastroenterology, Hepatology, Coloproctology

https://doi.org/10.22416/1382-4376-2021-31-1-54-63

Abstract

Aim. Assessment of the irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth syndrome (SIBO) interlinkage.

Key points. SIBO may represent a "peripheral" mechanism of IBS, aside to nonspecific inflammation, increased epithelial  permeability  and  local  immune  system  activation.  In  various  assays,  the  SIBO  rate  in  IBS  patients  was  4–46%  vs.  0–13%  in  an  intact  cohort.  A  limited  diagnosability  of  SIBO  obscures  the  SIBO–IBS  causal  interplay.  Impaired  motility  in  IBS  may  predispose  to  the  SIBO  development.  Proinflammatory  cytokines  and  mediators  in  SIBO, in turn, provoke visceral hypersensitivity and intense motility, the key IBS factors. Both conditions relate to qualitative  and  quantitative  changes  in  microbiota,  which  warrants  the  application  of  probiotic  Lactobacillus and Bifidobacterium strains.

Conclusion. Further research into the SIBO–IBS interface is required for developing optimal probiotic-based therapies.

Keywords: small intestinal bacterial overgrowth, irritable bowel syndrome, gut microbiota, probiotics, Lactobacillus, Bifidobacterium.

For citation:Ivashkin K.V., Grechishnikova V.R., Reshetova M.S., Ivashkin V.T. Irritable Bowel and Bacterial Overgrowth Syndromes: a Bacterial Link Hypothesis of Functional Disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(1):54-63. (In Russ.) https://doi.org/10.22416/1382-4376-2021-31-1-54-63

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Practical recommendations of scientific society for the study of human microbiome and the russian gastroenterological association on use of probiotics, prebiotics, synbiotics and functional foods in treatment and prevention of gastroenterological diseases in children and adults.

V. T. Ivashkin, I. V. Maev, D. I. Abdulganieva, S. A. Alekseenko, A. V. Gorelov, I. N. Zakharova, O. Yu. Zolnikova, N. Yu. Ivashkina, N. V. Korochanskaya, S. N. Mammayev, E. A. Poluektova, A. S. Trukhmanov, D. V. Usenko, Yu. P. Uspensky, V. V. Tsukanov, O. S. Shifrin, I. V. Berezhnaya, K. V. Ivashkin, T. L. Lapina,   R. V. Maslennikov,   S. V. Nikolaeva,   N. G. Sugyan,   A. I. Ulyanin

Russian Journal of Gastroenterology, Hepatology, Coloproctology

https://doi.org/10.22416/1382-4376-2021-31-2-65-91

Abstract

Aim. The practical guidelines are intended for primary care physicians, general practitioners, paediatricians, gastroenterologists and general internists to advance the treatment and prevention of gastroenterological diseases in adults and children in therapies with probiotics, prebiotics, synbiotics and their enriched functional foods.

Key points. Probiotics are live microorganisms that sustain health of the host when supplied in adequate amounts. Prebiotics include human-indigestible but accessible to gut microbiota substances expediting specific changes in the composition and/or activity of gastrointestinal microbiota that favour the host health. The mechanism of probiotic action comprises the quorum resistance maintenance, nutrient substrate metabolism and end metabolite recycling, macroorganism-sustaining substrate production, as well as the mediation of local and adaptive immune responses.

The Russian Federation regulates market differently for biologically active food additives (BAFA), medicinal products (drugs) and functional food products (FFP). We overview the probiotic strains regulated in Russia as BAFAs, drugs and FFPs and provide recommendations on the use of these strains in treatment and prevention of gastroenterological diseases in children and adults.

Conclusion. The clinical efficacy of probiotics, prebiotics, synbiotics and fortified functional foods depends on the prebiotic and strain properties and is verified in appropriate comparative clinical trials. Not all probiotics registered in Russia as BAFAs, drugs and FFPs have a strain identity, which provides no warranty of the clinical effect expected. The FFP legislation demands improved regulation mechanisms and control for therapeutic efficacy.

Keywords: probiotic, probiotic strain, prebiotic, symbiotic, functional food, functional food ingredient, acute diarrhea, antibiotic-associated diarrhea, C. difficile-associated disease, H. pylori eradication, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, pouchitis, irritable bowel syndrome, functional constipation, functional dyspepsia, diarrhoea prevention, hepatic encephalopathy, gastroenteritis

For citation: Ivashkin V.T., Maev I.V., Abdulganieva D.I., Alekseenko S.A., Gorelov A.V., Zakharova I.N., Zolnikova O.Yu., Ivashkina N.Yu., Korochanskaya N.V., Mammayev S.N., Poluektova E.A., Trukhmanov A.S., Usenko D.V., Uspensky Yu.P., Tsukanov V.V., Shifrin O.S., Berezhnaya I.V., Ivashkin K.V., Lapina T.L., Maslennikov R.V., Nikolaeva S.V., Sugyan N.G., Ulyanin A.I. Practical Recommendations of Scientific Society for the Study of Human Microbiome and the Russian Gastroenterological Association on Use of Probiotics, Prebiotics, Synbiotics and Functional Foods in Treatment and Prevention of Gastroenterological Diseases in Children and Adults. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(2):65-91. (In Russ.) https://doi.org/10.22416/1382-4376-2021-31-2-65-91

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Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

V.T. Ivashkin, I.V. Maev, Yu.A. Shelygin, E.K. Baranskaya, S.S. Belous, E.A. Belousova, A.G. Beniashvili, S.V. Vasilyev, A.V. Veselov, E.G. Grigoryev, N.V. Kostenko, V.N. Kashnikov, V.F. Kulikovskiy, I.D. Loranskaya, O.S. Lyashenko,  E.A. Poluektova, V. G. Rumyantsev, V. M. Timerbulatov,   O. Yu. Fomenko, D. A. Khubezov, E. Yu. Chashkova, G. I. Chibisov, M. V. Shapina,  A.A. Sheptulin, O. S. Shifrin,   A. S. Trukhmanov,   O. P. Alekseeva, S. A. Alekseenko, A. Yu. Baranovsky, O. Yu. Zolnikova, N. V. Korochanskaya, S.N. Mammayev, I.B. Khlynov, V.V. Tsukanov

Russian Journal of Gastroenterology, Hepatology, Coloproctology

https://doi.org/10.22416/1382-4376-2021-31-5-74-95 

Abstract

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).

Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.

Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants.

Keywords: irritable bowel syndrome, diarrhoea, constipation

For citation:Ivashkin V.T., Maev I.V., Shelygin Yu.A., Baranskaya E.K., Belous S.S., Belousova E.A., Beniashvili A.G., Vasilyev S.V., Veselov A.V., Grigoryev E.G., Kostenko N.V., Kashnikov V.N., Kulikovskiy V.F., Loranskaya I.D., Lyashenko O.S., Poluektova E.A., Rumyantsev V.G., Timerbulatov V.M., Fomenko O.Yu., Khubezov D.A., Chashkova E.Yu., Chibisov G.I., Shapina M.V., Sheptulin A.A., Shifrin O.S., Trukhmanov A.S., Alekseeva O.P., Alekseenko S.A., Baranovsky A.Yu., Zolnikova O.Yu., Korochanskaya N.V., Mammayev S.N., Khlynov I.B., Tsukanov V.V. Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(5):74-95. (In Russ.) https://doi.org/10.22416/1382-4376-2021-31-5-74-95

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Early viral versus late antibiotic-associated diarrhea in novel coronavirus infection

Roman Maslennikov, Andrey Svistunov, Vladimir Ivashkin, Anna Ufimtseva, Elena Poluektova, Irina Efremova, Anatoly Ulyanin, Alexey Okhlobystin, Svetlana Kardasheva, Anastasia Kurbatova, Anna Levshina, Diana Grigoriadis, Shamil Magomedov, Natiya Dzhakhaya, Oleg Shifrin, Maria Zharkova, Elena Yuryeva, Nataliya Kokina, Manana Shirtladze, Olga Kiseleva

Medicine (Baltimore) 

doi: 10.1097/MD.0000000000027528 

Abstract

Diarrhea is one of the manifestations of the novel coronavirus disease (COVID-19), but it also develops as a complication of massive antibiotic therapy in this disease. This study aimed to compare these types of diarrhea.

We included patients with COVID-19 in a cohort study and excluded patients with chronic diarrhea, laxative use, and those who died during the first day of hospitalization.

There were 89 (9.3%), 161 (16.7%), and 731 (75.7%) patients with early viral, late antibiotic-associated, and without diarrhea, respectively. Late diarrhea lasted longer (6 [4–10] vs 5 [3–7] days, P < .001) and was more severe. Clostridioides difficile was found in 70.5% of tested patients with late diarrhea and in none with early diarrhea. Presence of late diarrhea was associated with an increased risk of death after 20 days of disease (P = .009; hazard ratio = 4.7). Patients with late diarrhea had a longer hospital stay and total disease duration, and a higher proportion of these patients required intensive care unit admission. Oral amoxicillin/clavulanate (odds ratio [OR] = 2.23), oral clarithromycin (OR = 3.79), and glucocorticoids (OR = 4.41) use was a risk factor for the development of late diarrhea, while ceftriaxone use (OR = 0.35) had a protective effect. Before the development of late diarrhea, decrease in C-reactive protein levels and increase in lymphocyte count stopped but the white blood cell and neutrophil count increased. An increase in neutrophils by >0.6 × 109 cells/L predicted the development of late diarrhea in the coming days (sensitivity 82.0%, specificity 70.8%, area under the curve = 0.791 [0.710–0.872]).

Diarrhea in COVID-19 is heterogeneous, and different types of diarrhea require different management.

Keywords: antibiotic-associated diarrhea, COVID-19, diarrhea, mortality

For citation: Maslennikov R, Svistunov A, Ivashkin V, Ufimtseva A, Poluektova E, Efremova I, Ulyanin A, Okhlobystin A, Kardasheva S, Kurbatova A, Levshina A, Grigoriadis D, Magomedov S, Dzhakhaya N, Shifrin O, Zharkova M, Yuryeva E, Kokina N, Shirtladze M, Kiseleva O. Early viral versus late antibiotic-associated diarrhea in novel coronavirus infection. Medicine (Baltimore). 2021 Oct 15;100(41):e27528. doi: 10.1097/MD.0000000000027528. PMID: 34731146; PMCID: PMC8519250.

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Probiotics in hepatology: An update

Roman Maslennikov, Vladimir Ivashkin, Irina Efremova, Elena Poluektova, and Elena Shirokova

World Journal of Hepatology 

doi: 10.4254/wjh.v13.i9.1154

Abstract

The gut–liver axis plays an important role in the pathogenesis of various liver diseases. Probiotics are living bacteria that may be used to correct disorders of this axis. Notable progress has been made in the study of probiotic drugs for the treatment of various liver diseases in the last decade. It has been proven that probiotics are useful for hepatic encephalopathy, but their effects on other symptoms and syndromes of cirrhosis are poorly studied. Their 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 described. The 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 findings. The 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.

Keywords: 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

For citation: Maslennikov R, Ivashkin V, Efremova I, Poluektova E, Shirokova E. Probiotics in hepatology: An update. World J Hepatol 2021; 13(9): 1154-1166 [PMID: 34630882 DOI: 10.4254/wjh.v13.i9.1154]

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Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial

Vladimir Ivashkin, Victor Fomin, Sergey Moiseev, Michail Brovko, Roman Maslennikov, Anatoly Ulyanin, Victoria Sholomova, Maria Vasilyeva, Elizaveta Trush, Oleg Shifrin, Elena Poluektova

Probiotics and antimicrobial proteins 

https://doi.org/10.1007/s12602-021-09858-5

Abstract

The treatment of coronavirus disease (COVID-19) and COVID-19-associated diarrhea remains challenging. This study aimed to evaluate the efficacy of a multi-strain probiotic in the treatment of COVID-19. This was a randomized, controlled, single-center, open-label trial (NCT04854941). Inpatients with confirmed COVID-19 and pneumonia were randomly assigned to a group that received a multi-strain probiotic (PRO group) or to the control group (CON group). There were 99 and 101 patients in the PRO and CON groups, respectively. No significant differences in mortality, total duration of disease and hospital stay, incidence of intensive care unit admission, need for mechanical ventilation or oxygen support, liver injury development, and changes in inflammatory biomarker levels were observed between the PRO and CON groups among all included patients as well as among subgroups delineated based on age younger or older than 65 years, and subgroups with chronic cardiovascular diseases and diabetes. Diarrhea on admission was observed in 11.5% of patients; it resolved earlier in the PRO group than in the CON group (2 [1-4] vs. 4 [3-6] days; p = 0.049). Hospital-acquired diarrhea developed less frequently in the PRO group than in the CON group among patients who received a single antibiotic (0% vs. 12.5%; p = 0.023) unlike among those who received > 1 antibiotic (10.5% vs. 13.3%; p = 0.696). The studied probiotic had no significant effect on mortality and changes in most biomarkers in COVID-19. However, it was effective in treating diarrhea associated with COVID-19 and in preventing hospital-acquired diarrhea in patients who received a single antibiotic.

Keywords: COVID-19; Diarrhea; Liver; Mortality; Probiotics.

For citation:Ivashkin, V., Fomin, V., Moiseev, S. et al. Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial. Probiotics & Antimicro. Prot. (2021). https://doi.org/10.1007/s12602-021-09858-5

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Disruption of the pro-inflammatory, anti-inflammatory cytokines and tight junction proteins expression, associated with changes of the composition of the gut microbiota in patients with irritable bowel syndromе

V. Ivashkin, Y. Poluektov ,E. Kogan, O. Shifrin, A. Sheptulin, A. Kovaleva, A. Kurbatova, G. Krasnov, E. Poluektova

PLoSONE

https://doi.org/10.1371/journal.pone.0252930

Abstract

Background:

Irritable bowel syndrome (IBS) is a pathologic condition characterized by changes in gut microbiome composition, low-grade inflammation, and disruption of intestinal wall permeability. The interaction between the gut microbiome and the disease manifestation remains unclear. The changing of tight junction proteins and cytokines expression throughout the gastrointestinal tract in IBS patients has not been studied yet.

Aim: 

To assess the changes of gut microbiome composition, tight junction proteins, and cytokines expression of intestinal mucosa from the duodenum to the distal part of the colon in IBS patients and healthy volunteers.

Methods:

In 31 IBS patients (16 patients with IBS-D; 15 patients with IBS-C) and 10 healthy volunteers the expression of CLD-2, CLD-3, CLD-5, IL-2, IL-10, and TNF-αin mucosal biopsy specimens was determined by morphological and immune-histochemical methods. The qualitative and quantitative composition of the intestinal microbiota was assessed based on 16S rRNA gene sequencing in both groups of patients.

Results:

The expression of IL-2 and TNF-αwas significantly increased in IBS patients compared with the controls (p<0.001), with a gradual increase from the duodenum to the sigmoid colon. The expression of IL-10, CLD-3, and CLD-5 in mucosal biopsy specimens of these patients was lower than in the control group (p<0.001). Increased ratios of Bacteroidetes and decreased ratios of Firmicutes were noted in IBS patients compared to healthy volunteers (p<0.05).

Conclusion

IBS patients have impaired gut permeability and persisting low-grade inflammation throughout the gastrointestinal tract. Changes in the gut microbiota may support or exacerbate these changes.

For citation: Ivashkin V, Poluektov Y, Kogan E, Shifrin O, Sheptulin A, Kovaleva A, et al. (2021) Disruption of the pro-inflammatory, anti-inflammatory cytokines and tight junction proteins expression, associated with changes of the composition of the gut microbiota in patients with irritable bowel syndrome. PLoS ONE 16(6): e0252930. https://doi.org/10.1371/journal.pone.0252930

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A clinical variant of coronavirus disease 2019 with diarrhoea as the initial symptom compared with other variants

Roman Maslennikov, Vladimir Ivashkin, Anna Ufimtseva, Elena Poluektova

Minerva Gastroenterologica e Dietologica

DOI: 10.23736/S2724-5985.21.02827-0

Abstract No abstract available

For citation: Maslennikov R, Ivashkin V, Ufimtseva A, Poluektova E. A clinical variant of coronavirus disease 2019 with diarrhoea as the initial symptom compared with other variants. Minerva Gastroenterol (Torino). 2021 Apr 15. doi: 10.23736/S2724-5985.21.02827-0. Epub ahead of print. PMID: 33856143.

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

Roman Maslennikov, Vladimir Ivashkin, Irina Efremova, Aliya Alieva, Ekaterina Kashuh, Ekaterina Tsvetaeva, Elena Poluektova, Elena Shirokova, Konstantin Ivashkin

World Journal of Hepatology

doi: 10.4254/wjh.v13.i5.557

Abstract

Background:

Gut dysbiosis is common in cirrhosis.

Aim:

To study the influence of gut dysbiosis on prognosis in cirrhosis.

Methods:

The case-control study included 48 in-patients with cirrhosis and 21 healthy controls. Stool microbiome was assessed using 16S ribosomal ribonucleic acid gene sequencing. We 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 non-severe dysbiosis. The follow-up period was 4 years.

Results:

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 survivors. 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.

Keywords: Cirrhosis, Dysbiosis, Gut, ROC-analysis, Microbiota, Microbiome, Gut-liver axis

For citation: Maslennikov R, Ivashkin V, Efremova I, Alieva A, Kashuh E, Tsvetaeva E, Poluektova E, Shirokova E, Ivashkin K. Gut dysbiosis is associated with poorer long-term prognosis in cirrhosis. World J Hepatol 2021; 13(5): 557-570 [PMID: 34131470 DOI: 10.4254/wjh.v13.i5.557]

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Diarrhoea in adults with coronavirus disease—beyond incidence and mortality: a systematic review and meta-analysis

Roman Maslennikov, Elena Poluektova, Vladimir Ivashkin, Andrey Svistunov

Infectious Diseases

https://doi.org/10.1080/23744235.2021.1885733

Abstract

Aim

Diarrhoea is a relatively common manifestation of coronavirus disease (COVID-19), but there is no systematic review which comprehensively describes it beyond its incidence and impact on prognosis. This study aims to provide a detailed systematic review of diarrhoea in adults with COVID-19.

Methods

A PUBMED and Scopus search (until 7 September 2020) was performed. Studies that were limited to describing incidence of diarrhoea and its effect on prognosis were excluded.

Results

Twenty-six papers including 7860 patients with COVID-19 were subjected to synthesis. Mean duration of diarrhoea was 4.2 (3.6–4.9) days (range 1–16 days), whereas mean bowel movement count was 4.6 (3.8–5.3) and maximum was 20 per day. Diarrhoea started on an average 5.1 (3.8–6.5) days after disease onset but was the first manifestation in 4.3% patients. Stool occult blood was detected in 6.8% of patients with diarrhoea, while 53.3% cases had watery diarrhoea. Patients with diarrhoea also had elevated faecal calprotectin. Viral genome in faeces was detected more often in patients with diarrhoea and most often in patients without respiratory symptoms. Fever, myalgia and respiratory symptoms were observed with the same incidence in patients with and without diarrhoea. Similarly, there were no differences noted in complete blood count and most inflammation biomarkers between patients with and without diarrhoea. However, nausea, vomiting abdominal pain, sneezing and headache were more common in patients with diarrhoea. Diarrhoea was the main manifestation of COVID-19 in 6.1% of cases and this form of the disease had specific features.

Conclusions

Diarrhoea in COVID-19 needs further investigation.

Keywords: COVID-19diarrhoeasystematic reviewmeta-analysis

For citation: Roman Maslennikov , Elena Poluektova , Vladimir Ivashkin & Andrey Svistunov (2021): Diarrhoea in adults with coronavirus disease—beyond incidence and mortality: a systematic review and meta-analysis, Infectious Diseases, DOI:10.1080/23744235.2021.1885733

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Clinical validation of the “7 × 7” questionnaire for patients with functional gastrointestinal disorders

Vladimir Ivashkin,  Arkady Sheptulin,  Oleg Shifrin,  Elena Poluektova,  Chavdar Pavlov,  Konstantin Ivashkin,  Alexandra Drozdova,  Olga Lyashenko,  Alexandr Korolev

Journal of Gastroenterology and Hepatology

https://doi.org/10.1111/jgh.14546

Abstract

Background and Aim

Physicians use different scales and questionnaires to assess the severity of clinical symptoms in patients with functional gastrointestinal disorders. The current study aimed to validate the “7 × 7” questionnaire for assessment of severity of the symptoms as a tool for the efficacy of treatment of functional gastrointestinal disorders, using the Clinical Global Impressions scale as the reference standard.

Methods

Fifty inpatients aged from 18 to 64 with a confirmed diagnosis of irritable bowel syndrome (26 patients, 52%), functional dyspepsia (15 patients, 30%), or both (9 patients, 18%) were prospectively enrolled in the study. We used both the 7 × 7 questionnaire and the Clinical Global Impressions scale before and after 28 days of stable treatment.

Results

Our study revealed a significant correlation between the 7 × 7 questionnaire and the Clinical Global Impressions scale results in assessment of severity of the clinical symptoms and their dynamics during treatment. The 7 × 7 questionnaire showed sensitivity of 74.5% and specificity of 54.1% for evaluating patients with mild to severe disease and 66.6% and 76%, respectively, for evaluating patients with moderate to severe disease. The Cronbach's alpha coefficient was 0.719. The intraclass correlation coefficient among participants in whom the condition remained the same was 0.973 (12 participants [24.5%]).

Conclusions

The 7 × 7 questionnaire is a convenient, sensitive, and reliable tool for assessing the severity of symptoms and treatment efficacy in people with functional gastrointestinal disorders.

Keywords: “7 × 7” questionnaire, Clinical Global Impressions scale, functional dyspepsia, irritable bowel syndrome, symptoms dynamics

For citation: Ivashkin V, Sheptulin A, Shifrin O, Poluektova E, Pavlov C, Ivashkin K, Drozdova A, Lyashenko O, Korolev A. Clinical validation of the “7 × 7” questionnaire for patients with functional gastrointestinal disorders. J Gastroenterol Hepatol. 2019;34(6):1042–8.

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The Evolution of Human Probiotics: Challenges and Prospects

Elizaveta Trush, Elena Poluektova, Allan Beniashvilli, Oleg Shifrin, Yuri Poluektov, Vladimir Ivashkin

Probiotics and antimicrobial proteins

https://doi.org/10.1007/s12602-019-09628-4

Abstract

In recent years, the intestinal microbiota has been found to greatly influence a number of biological processes important for human health and longevity. Microbial composition changes easily in response to external factors, such as an unbalanced diet, lack of physical activity, and smoking. Probiotics are a key factor in maintaining the optimal composition of the intestinal microbiota. However, a number of important questions related to probiotics, such as indication for prescription, comparative efficacy of monostrain and multistrain probiotics, methods of delivery, and shelf life, remain unresolved. The aim of this review is to highlight existing issues regarding probiotic production and their prescription. The review presents the most recent findings regarding advantages and efficacy of monostrain and multistrain probiotics, preservation of probiotic strains in capsules and microcapsules, production of probiotics in the form of biofilms for improved efficacy and survival, and results of clinical studies evaluating the benefits of probiotics against different pathologies. We believe that this work will be of interest to physicians and researchers alike and will promote the development of new probiotics and ensuing regimens aimed at the treatment of various diseases.

Keywords:Biofilm, efficacy,  monostrain and multistrain probiotics, planktonic cells.

For citation: Trush, E.A., Poluektova, E.A., Beniashvilli, A.G. et al. The Evolution of Human Probiotics: Challenges and Prospects. Probiotics & Antimicro. Prot. 12, 1291–1299 (2020). https://doi.org/10.1007/s12602-019-09628-4

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Roman Maslennikov, Chavdar Pavlov, Andrey Kotzev, Vladimir Ivashkin

Comptes Rendus de L'Academie Bulgare des Sciences

DOI: 10.7546/CRABS.2020.04.15 

Abstract

Small intestinal bacterial overgrowth (SIBO) and vasodilatation are common in cirrhosis. The aim is to study the influence of SIBO on the development of vasodilatation in cirrhosis. Fifty patients with cirrhosis and 15 healthy controls were enrolled in a pilot prospective study. All participants underwent lactulose hydrogen breath test for SIBO and echocardiography with simultaneous assessment of blood pressure and heart rate. Systemic vascular resistance was calculated. Blood C-reactive protein was measured. Systemic vascular resistance was lower in patients with SIBO in comparison with those without SIBO and healthy controls (1312 ± 352 dyn s cm-5 vs. 1704 ± 424 dyn s cm-5 and 1648 ± 272 dyn s cm-5; p = 0.001 and p = 0.006). There was no significant difference between patients without SIBO and healthy controls in systemic vascular resistance ( p = 0.874). Systemic inflammatory response was detected in 14/26 patients with SIBO and in 2/24 patients without SIBO ( p = 0.001). Among participants with cirrhosis, there was a negative correlation between blood C-reactive protein and systemic vascular resistance ( r = ‑0.367; p = 0.009). SIBO is associated with vasodilation in cirrhosis and may be a principal factor causing it through systemic inflammation.

Key words: cirrhosis, small intestinal bacterial overgrowth, vasodilation

For citation: Maslennikov R, Pavlov C, Kotzev A, Ivashkin V. Small intestinal bacterial overgrowth is associated with vasodilatation in cirrhosis. Comptes rendus de l’Acade'mie bulgare des Sciences, Vol 73, No4, pp.553-558

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Small intestinal bacterial overgrowth in cirrhosis: systematic review and meta-analysis

Roman Maslennikov, Chavdar Pavlov, Vladimir Ivashkin

Hepatology international

https://doi.org/10.1007/s12072-018-9898-2

Abstract

Background

Small intestinal bacterial overgrowth (SIBO) was detected in cirrhosis in many studies. The aim is to perform a systematic review and meta-analysis on the prevalence of SIBO in cirrhosis and on the relationship of SIBO with features of cirrhosis.

Methods

PUBMED search (until 14 January 2018) was performed. Specific search terms were: ‘(cirrhosis) AND (SIBO OR bacterial overgrowth)’. Studies not relating to cirrhosis or SIBO, animal studies, and non-original articles were excluded. A meta-analysis of all studies was performed using a random-effects model.

Results

117 references were identified by the PUBMED search. 3 references were added after handsearching the reference lists of all the articles. 99 references were excluded. 21 studies (included in total 1264 cirrhotics and 306 controls) remained for qualitative analysis and quantitative synthesis. Prevalence of SIBO for cirrhosis was 40.8% (95% CI 34.8–47.1), while the prevalence of SIBO for controls was 10.7% (95% CI 5.7–19.0). OR 6.83 (95% CI 4.16–11.21; p < 0.001). Prevalence of SIBO for decompensated cirrhosis was higher than prevalence of SIBO for compensated cirrhosis (50.5% vs. 31.2%; p < 0.001). SIBO in cirrhosis was associated with ascites (p < 0.001), minimal hepatic encephalopathy (p = 0.001), bacterial translocation (p = 0.026), spontaneous bacterial peritonitis (p = 0.008), prolonged orocecal transit time (p < 0.001), and was not associated with hypocoagulation. Further studies are required to clarify the relationship of SIBO with hyperbilirubinemia, hypoalbuminemia, overt hepatic encephalopathy in past, esophageal varices and systemic inflammation.

Conclusion

Small intestinal bacterial overgrowth is more often detected in cirrhosis than in healthy persons and is associated with some features of cirrhosis.

Keywords: SIBO, Cirrhosis, Systematic review, Meta-analysis.

For citation: Maslennikov, R., Pavlov, C. & Ivashkin, V. Small intestinal bacterial overgrowth in cirrhosis: systematic review and meta-analysis. Hepatol Int 12, 567–576 (2018). https://doi.org/10.1007/s12072-018-9898-2

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Roman Maslennikov, Chavdar Pavlov, Vladimir Ivashkin

Turkish Journal of Gastroenterology

DOI: 10.5152 / tjg.2019.18551

Abstract

Background/aims: Small intestinal bacterial overgrowth (SIBO) and hemodynamic changes are common in cirrhosis. We wanted to examine our hypothesis whether SIBO leads to hemodynamic changes in cirrhosis.

Materials and methods: A total of 50 patients with cirrhosis and 15 healthy controls were enrolled in a pilot prospective study. All participants underwent the lactulose hydrogen breath test for SIBO and echocardiography with a simultaneous assessment of blood pressure and heart rate. Cardiac output and systemic vascular resistance were calculated.

Results: Study participants with SIBO had a lower systolic blood pressure and systemic vascular resistance compared to those without SIBO and to healthy controls (110.2±12.3 mmHg vs. 126.2±21.0 mmHg and 121.2±9.8 mmHg; p=0.005 and p=0.011, respectively; 1312±352 dyn•s•cm-5 vs. 1704±424 dyn•s•cm-5 and 1648±272 dyn•s•cm-5; p=0.001 and p=0.006, respectively), but a higher cardiac output (5.38±1.41 l/min vs. 4.52±1.03 l/min and 4.40±0.68 l/min; p=0.034 and p=0.041, respectively) and C-reactive protein (10.5[1.2-16.5] mg/l vs. 2.8[0.6-9.1] mg/l; p=0.028; no comparison with healthy controls). There were no significant differences between patients without SIBO and healthy controls with regard to systolic blood pressure (p=0.554), systemic vascular resistance (p=0.874), and cardiac output (p=0.795). SIBO was associated with vasodilation and hyperdynamic circulation in decompensated cirrhosis (p=0.002; p=0.012), but not in compensated cirrhosis (p=1.000; p=0.474).

Conclusions: SIBO is associated with hyperdynamic circulation and other hemodynamic changes in cirrhosis and may be a principal factor causing these through systemic inflammation.

Keywords: Cirrhosis, vasodilation, gut microbiota, hemodynamics, systemic inflammation

For citation: Maslennikov R, Pavlov C, Ivashkin V. Is small intestinal bacterial overgrowth a cause of hyperdynamic circulation in cirrhosis? Turk J Gastroenterol 2019; 30(11):964-75.

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Oxana Zolnikova, Inna Komkova, Nino Potskherashvili, Alexander Trukhmanov, Vladimir Ivashkin

Italian Journal of Medicine

https://doi.org/10.4081/itjm.2018.931

Abstract

We have reviewed the currently published results on a role of the gut microflora in a prevention of acute respiratory infections. The main biological properties of probiotic bacteria are presented in a context of their modulating activity on an inflammatory immune response. Available data on the reduction of a possible risk, duration, and severity of respiratory infection symptoms during a probiotic medication intake were analyzed. Potential antiviral probiotic mechanisms have been reviewed and discussed.

Keywords: Acute respiratory infections, lung microbiome, intestinal microbiome, immunomodulation, probiotic.

For citation: Zolnikova, O., Komkova, I., Potskherashvili, N., Trukhmanov, A., & Ivashkin, V. (2018). Application of probiotics for acute respiratory tract infections. Italian Journal of Medicine, 12(1), 32-38. https://doi.org/10.4081/itjm.2018.931

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Vladimir Ivashkin, Oxana Zolnikova, Nino Potskherashvili, Alexander Trukhmanov, Natalia Kokina, Natiya Dzhakhaya

Italian Journal of Medicine

https://doi.org/10.4081/itjm.2018.1040

Abstract

The efficacy of a gut microbiota control was investigated for patients with atopic asthma. 45 patients with atopic asthma were included in the study. The results of our clinical and lab tests, pulmonary function tests and the lactulose hydrogen breath tests have been presented to evaluate small intestine bacterial overgrowth (SIBO). Under the standard SIBO’s therapy (long-acting beta-agonists, inhaled glucocorticoids), the first group (15 patients) had being tested with Rifaximin for the SIBO therapy during 7 days. The second group (15 patients) had been tested with Rifaximin and with a succeeding probiotics therapy for three months (B. bifidum, B. longum, B. infantis, L. rhamnosus). SIBO was diagnosed for 30 (67%) patients. We have detected a higher IgE level (P<0.01), a higher eosinophils level (P<0.001) in sputum and more significant decrease of FEV1 (P<0.01) in SIBO(+). The IgE level in patients was decreased (P<0.01) after the complex SIBO therapy both for the Rifaximin therapy group (P<0.05) and for the Rifaximin + Probiotic therapy group (P<0.05). A dramatic decrease of the IgE level (P<0.05) had been induced by probiotics and it was confirmed by the control testing results with a high statistical accuracy for the observed groups of patients. We did not detect any changes for the patients without SIBO (P=0.46), those who had been treated with a standard therapy. A decrease in the number of patient hospitalization was defined by the treatment with probiotics after SIBO therapy (P<0.05). So, SIBO is a significant factor aggravating the atopic asthma in patients. The gut microflora correction with probiotics therapy has been accompanied by a statistical reliability improvement for the immune response and spirometry, as well as by a decrease in the number of hospitalizations for these patients during the year.

Keywords: Gut microbiota, atopic asthma, small intestine bacterial overgrowth, immunomodulation, probiotic.

For citation: Ivashkin, V., Zolnikova, O., Potskherashvili, N., Trukhmanov, A., Kokina, N., & Dzhakhaya, N. (2018). A correction of a gut microflora composition for the allergic bronchial asthma complex therapy. Italian Journal of Medicine, 12(4), 260-264. https://doi.org/10.4081/itjm.2018.1040

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Vladimir Ivashkin, Maria Fadeeva, Manana Skhirtladze, Oxana Zolnikova

Italian Journal of Medicine

https://doi.org/10.4081/itjm.2020.1185

Abstract

In this review, we have considered and discussed the existing data to achieve a deeper understanding of the role of intestinal microbiota in the development and progression of chronic heart failure (CHF). The key moments of the CHF pathogenesis (an imbalance of neurohumoral systems, inflammatory theory and metabolic disorders) and the respective changes of the intestinal microflora composition were compared. Here, we also present the latest results of the positive influence of the microflora modulations on the course and prognosis of CHF with the prescribing antibiotics, probiotics and prebiotics.

Keywords: Intestinal microbiota, chronic heart failure, probiotics, cytokines.

For citation: Ivashkin, V., Fadeeva, M., Skhirtladze, M., & Zolnikova, O. (2020). Intestinal microbiota in the pathogenesis of chronic heart failure. Italian Journal of Medicine, 14(1), 1-8. https://doi.org/10.4081/itjm.2020.1185

Vladimir Ivashkin, Oleg Medvedev, Elena Poluektova, Anna Kudryavtseva, Ildar Bakhtogarimov, Anna Karchevskaya

Russian Journal of Gastroenterology, Hepatology, Coloproctology

(https://www.gastro-j.ru/jour?locale=en_US)

https://doi.org/10.22416/1382-4376-2022-32-2-19-34

Abstract

Aim: To review the main methods of intestinal microbiota studying.

Key  points.  Currently,  molecular  genetic  methods  are  used  mainly  for  basic  research  and  do  not  have  a  unified  protocol for data analysis, which makes it difficult to implement them in clinical practice. Measurement of short chain fatty acids (SCFA) concentrations in plasma provides the data, which can serve as an indirect biomarker of the colonic microbiota  composition.  However,  currently  available  evidence  is  insufficient  to  relate  the  obtained  values  (SCFA  levels and ratio) to a particular disease with a high degree of certainty. Trimethylamine N-oxide (TMAO) levels in the blood plasma and urine can also reflect the presence of specific bacterial clusters containing genes Cut, CntA/CntB and YeaW/YeaX. Therefore, further studies are required to reveal possible correlations between certain disorders and such parameters as the composition of gut microbiota, dietary patterns and TMAO concentration. Gas biomarkers, i.e.  hydrogen,  methane  and  hydrogen  sulphide,  have  been  studied  in  more  detail  and  are  better  understood  as  compared  to  other  biomarkers  of  the  gut  microbiome  composition  and  functionality.  The  main  advantage  of  gas  biomarkers  is  that  they  can  be  measured  multiple  times  using  non-invasive  techniques.  These  measurements  provide  information  on  the  relative  proportion  of  hydrogenic  (i.e.  hydrogen  producing)  and  hydrogenotrophic  (i.e.  methanogenic  and  sulfate-reducing)  microorganisms.  In  its  turn,  this  opens  up  the  possibility  of  developing  new  approaches to correction of individual microbiota components. Conclusions.  Integration  of  the  data  obtained  by  gut  microbiota  studies  at  the  genome,  transcriptome  and  metabolome  levels  would  allow  a  comprehensive  analysis  of  microbial  community  function  and  its  interaction  with  the human organism. This approach may increase our understanding of the pathogenesis of various diseases as well open up new opportunities for prevention and treatment.

Keywords: microbiota, microbiome, metabolome, transcriptome, sequencing, trimethylamine, trimethylaminoxide, short-chain fatty acids, hydrogen, methane, hydrogen sulfide

For citation: Ivashkin  V.T.,  Medvedev  O.S.,  Poluektova  E.A.,  Kudryavtseva  A.V.,  Bakhtogarimov  I.R.,  Karchevskaya  A.E.  Direct  and  Indirect  Methods  for  Studying  Human  Gut  Microbiota.  Russian  Journal  of  Gastroenterology,  Hepatology,  Coloproctology.  2022;32(2):19–34. https://doi.org/10.22416/1382-4376-2022-32-2-19-34