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Cho MY, Eom JH, Choi EM, Yang SJ, Lee D, Kim YY, Kim HS, Hwang I. Recent advances in therapeutic probiotics: insights from human trials. Clin Microbiol Rev 2025:e0024024. [PMID: 40261032 DOI: 10.1128/cmr.00240-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/24/2025] Open
Abstract
SUMMARYRecent advances in therapeutic probiotics have shown promising results across various health conditions, reflecting a growing understanding of the human microbiome's role in health and disease. However, comprehensive reviews integrating the diverse therapeutic effects of probiotics in human subjects have been limited. By analyzing randomized controlled trials (RCTs) and meta-analyses, this review provides a comprehensive overview of key developments in probiotic interventions targeting gut, liver, skin, vaginal, mental, and oral health. Emerging evidence supports the efficacy of specific probiotic strains and combinations in treating a wide range of disorders, from gastrointestinal (GI) and liver diseases to dermatological conditions, bacterial vaginosis, mental disorders, and oral diseases. We discuss the expanding understanding of microbiome-organ connections underlying probiotic mechanisms of action. While many clinical trials demonstrate significant benefits, we acknowledge areas requiring further large-scale studies to establish definitive efficacy and optimal treatment protocols. The review addresses challenges in standardizing probiotic research methodologies and emphasizes the importance of considering individual variations in microbiome composition and host genetics. Additionally, we explore emerging concepts such as the oral-gut-brain axis and future directions, including high-resolution microbiome profiling, host-microbe interaction studies, organoid models, and artificial intelligence applications in probiotic research. Overall, this review offers a comprehensive update on the current state of therapeutic probiotics across multiple domains of human health, providing insights into future directions and the potential for probiotics to revolutionize preventive and therapeutic medicine.
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Affiliation(s)
- Mu-Yeol Cho
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
| | - Je-Hyun Eom
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
| | - Eun-Mi Choi
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
| | | | - Dahye Lee
- Department of Orthodontics, Apple Tree Dental Hospital, Goyang-si, South Korea
| | - Young Youn Kim
- Department of Oral and Maxillofacial Surgery, Apple Tree Dental Hospital, Goyang-si, South Korea
| | - Hye-Sung Kim
- Department of Oral and Maxillofacial Surgery, Apple Tree Dental Hospital, Goyang-si, South Korea
| | - Inseong Hwang
- Apple Tree Institute of Biomedical Science, Apple Tree Medical Foundation, Goyang-si, South Korea
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Sakamaki A, Yokoyama K, Yamazaki H, Wakabayashi T, Kojima Y, Tominaga K, Tsuchiya A, Kamimura K, Yokoyama J, Terai S. Small Intestinal Bacterial Overgrowth Is a Predictor of Overt Hepatic Encephalopathy in Patients with Liver Cirrhosis. J Clin Med 2025; 14:1491. [PMID: 40094949 PMCID: PMC11901010 DOI: 10.3390/jcm14051491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 02/10/2025] [Accepted: 02/21/2025] [Indexed: 03/19/2025] Open
Abstract
Objective: Liver cirrhosis (LC) progression induces intestinal microbiota abnormalities, such as small intestinal bacterial overgrowth (SIBO), and these changes lead to the inflow of gut pathogens and their degradation products into the vessels, causing cirrhotic complications such as hepatic encephalopathy (HE). Methods: To clarify the relationship between the development of overt HE and SIBO, we conducted a three-year observation after assessment of SIBO in patients with LC. Results: In the analysis of 107 patients, with a mean follow-up duration of 29.4 months, 31 were diagnosed with SIBO and 30 with covert HE. In the Cox multivariate regression analysis for prognosis, the Child-Pugh score, blood urea nitrogen level, and the Union for International Cancer Control (UICC) stage of hepatocellular carcinoma were derived using the following five factors: white blood cell count, blood urea nitrogen level, Child-Pugh score, UICC stage, and serum aspartate aminotransferase and alkaline phosphatase levels (p = 0.002, hazard ratio [HR] 3.733, 95% confidence interval [CI] 1.592-8.754, p = 0.001, HR 1.076, 95% CI 1.030-1.123, and p < 0.001, HR 2.767, 95% CI 1.780-4.302, respectively). Furthermore, in the Cox multivariate regression analysis for overt HE development, covert HE and methane-producing SIBO were derived using the following four factors: methane-producing SIBO, UICC stage, covert HE, and serum ammonia levels (p = 0.038, HR 5.008, 95% CI 1.096-22.892 and p = 0.006, HR 8.597, 95% CI 1.881-39.291, respectively). Conclusions: M-SIBO positivity was a significant predictor of overt HE.
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Affiliation(s)
- Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Kunihiko Yokoyama
- Division of Gastroenterology and Hepatology, Niigata Prefectural Hospital, Niigata 943-0192, Japan;
| | - Hanako Yamazaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Takuya Wakabayashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Yuichi Kojima
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Kentaro Tominaga
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
| | - Kenya Kamimura
- Department of General Medicine, Niigata University School of Medicine, Niigata 951-8510, Japan;
| | - Junji Yokoyama
- Division of Gastroenterology and Hepatology, Saiseikai Niigata Hospital, Niigata 950-1104, Japan;
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (H.Y.); (T.W.); (Y.K.); (K.T.); (A.T.)
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Idalsoaga F, Ayares G, Blaney H, Cabrera D, Chahuan J, Monrroy H, Matar A, Halawi H, Arrese M, Arab JP, Díaz LA. Neurogastroenterology and motility disorders in patients with cirrhosis. Hepatol Commun 2025; 9:e0622. [PMID: 39773873 PMCID: PMC11717532 DOI: 10.1097/hc9.0000000000000622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 11/21/2024] [Indexed: 01/11/2025] Open
Abstract
Neurogastroenterology and motility disorders are complex gastrointestinal conditions that are prevalent worldwide, particularly affecting women and younger individuals. These conditions significantly impact the quality of life of people suffering from them. There is increasing evidence linking these disorders to cirrhosis, with a higher prevalence compared to the general population. However, the link between neurogastroenterology and motility disorders and cirrhosis remains unclear due to undefined mechanisms. In addition, managing these conditions in cirrhosis is often limited by the adverse effects of drugs commonly used for these disorders, presenting a significant clinical challenge in the routine management of patients with cirrhosis. This review delves into this connection, exploring potential pathophysiological links and clinical interventions between neurogastroenterology disorders and cirrhosis.
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Affiliation(s)
- Francisco Idalsoaga
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Gustavo Ayares
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- Universidad Finis Terrae, Escuela de Medicina, Facultad de Medicina, Universidad Fines Terrae, Santiago, Chile
| | - Hanna Blaney
- MedStar Georgetown University Hospital, Medstar Transplant Hepatology Institute, Washington, District of Columbia, USA
| | - Daniel Cabrera
- Faculty of Medicine, Universidad de los Andes, Santiago, Chile
- Centro de Estudios e Investigación en Salud y Sociedad, Escuela de Medicina, Facultad de Ciencias Médicas, Universidad Bernardo O Higgins, Santiago, Chile
| | - Javier Chahuan
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
| | - Hugo Monrroy
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
| | - Ayah Matar
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Houssam Halawi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Marco Arrese
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Luis Antonio Díaz
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA
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Ott P, Eriksen PL, Kjærgaard K, Sørensen M, Thomsen KL, Vilstrup H. Down the road towards hepatic encephalopathy. The elusive ammonia- what determines the arterial concentration? Metab Brain Dis 2024; 40:48. [PMID: 39621139 PMCID: PMC11611965 DOI: 10.1007/s11011-024-01435-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 10/25/2024] [Indexed: 12/06/2024]
Abstract
Elevated arterial ammonia is associated with several complications of liver disease as it predicts mortality for in-patients and decompensation, hospitalization and death in out-patients with cirrhosis. In this review, our aim was to estimate how the individual organs contribute to arterial ammonia based on published data from human studies. The brain removes ammonia from arterial blood in a concentration-dependent fashion. Ammonia that is released from the gut to portal blood is mainly from metabolism of glutamine in the enterocytes using this as a source of energy. Ammonia produced by bacterial metabolism of urea and proteins only partially reach portal blood and is likely recycled into bacterial proteins. In general, the liver efficiently removes ammonia from arterial or portal blood in proportion to the delivered concentration. As a result,- and in some contrast to conventional wisdom-, the hepato-splanchnic region only contributes marginally to arterial ammonia; even during a simulated upper GI bleed. The only exception is acute liver failure where hepatocyte necrosis allows large quantities of portal ammonia to pass. The kidneys release ammonia from glutamine metabolism into systemic blood. The renal ammonia release increases during a simulated upper GI bleed or hypokalemia where it becomes a major source of elevated arterial ammonia. In the resting state, muscles remove ammonia in a concentration-dependent manner and muscles are the primary ammonia lowering organ in most situations with elevated arterial ammonia. During strenuous exercise, muscles produce large amounts of ammonia into systemic blood. Thus, the complete pattern of ammonia metabolism is very dynamic and illustrates the difficulties in designing ammonia lowering therapies.
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Affiliation(s)
- Peter Ott
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark.
| | - Peter Lykke Eriksen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
| | - Kristoffer Kjærgaard
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
| | - Michael Sørensen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
- Department of Internal Medicine, Viborg Regional Hospital, Viborg, Denmark
| | - Karen Louise Thomsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus N, DK-8200, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Sun S, Zhang G, Lv S, Sun J. Potential mechanisms of traditional Chinese medicine in the treatment of liver cirrhosis: a focus on gut microbiota. Front Microbiol 2024; 15:1407991. [PMID: 39234554 PMCID: PMC11371771 DOI: 10.3389/fmicb.2024.1407991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 07/29/2024] [Indexed: 09/06/2024] Open
Abstract
Cirrhosis, a pathological stage that develops from various chronic liver diseases, is characterized by liver fibrosis, pseudolobular formation, and chronic inflammation. When it progresses to the decompensated phase, the mortality rate of cirrhosis can reach 80%. The role of gut microbiota in the progression of liver diseases has received significant attention. Numerous studies have shown that regulating gut microbiota has significant therapeutic effects on preventing and reversing liver cirrhosis. This article reviewed the mechanisms by which gut microbiota influence liver cirrhosis, explaining the effective therapeutic effects of traditional Chinese medicine. Through multi-directional regulation involving signaling pathways, gut microbiota diversity, and restoration of intestinal barrier function, traditional Chinese medicine has been promising in ameliorating liver cirrhosis, providing treatment options and pharmacological guidance for the occurrence and development of liver cirrhosis.
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Affiliation(s)
- Siyuan Sun
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
| | - Guangheng Zhang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shimeng Lv
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jinhui Sun
- Gastroenterology Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Roszkowska P, Klimczak E, Ostrycharz E, Rączka A, Wojciechowska-Koszko I, Dybus A, Cheng YH, Yu YH, Mazgaj S, Hukowska-Szematowicz B. Small Intestinal Bacterial Overgrowth (SIBO) and Twelve Groups of Related Diseases-Current State of Knowledge. Biomedicines 2024; 12:1030. [PMID: 38790992 PMCID: PMC11117733 DOI: 10.3390/biomedicines12051030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 05/01/2024] [Accepted: 05/03/2024] [Indexed: 05/26/2024] Open
Abstract
The human gut microbiota creates a complex microbial ecosystem, characterized by its high population density, wide diversity, and complex interactions. Any imbalance of the intestinal microbiome, whether qualitative or quantitative, may have serious consequences for human health, including small intestinal bacterial overgrowth (SIBO). SIBO is defined as an increase in the number of bacteria (103-105 CFU/mL), an alteration in the bacterial composition, or both in the small intestine. The PubMed, Science Direct, Web of Science, EMBASE, and Medline databases were searched for studies on SIBO and related diseases. These diseases were divided into 12 groups: (1) gastrointestinal disorders; (2) autoimmune disease; (3) cardiovascular system disease; (4) metabolic disease; (5) endocrine disorders; (6) nephrological disorders; (7) dermatological diseases; (8) neurological diseases (9); developmental disorders; (10) mental disorders; (11) genetic diseases; and (12) gastrointestinal cancer. The purpose of this comprehensive review is to present the current state of knowledge on the relationships between SIBO and these 12 disease groups, taking into account risk factors and the causal context. This review fills the evidence gap on SIBO and presents a biological-medical approach to the problem, clearly showing the groups and diseases having a proven relationship with SIBO, as well as indicating groups within which research should continue to be expanded.
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Affiliation(s)
- Paulina Roszkowska
- Department of Diagnostic Immunology, Pomeranian Medical University, st. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (P.R.); (I.W.-K.)
| | - Emilia Klimczak
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
| | - Ewa Ostrycharz
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
- Doctoral School, University of Szczecin, st. A. Mickiewicz 16, 71-412 Szczecin, Poland
- Molecular Biology and Biotechnology Center, University of Szczecin, st. Wąska 13, 71-412 Szczecin, Poland
| | - Aleksandra Rączka
- Department of Genetics, West Pomeranian University of Technology, st. Aleja Piastów 45, 70-311 Szczecin, Poland; (A.R.); (A.D.)
| | - Iwona Wojciechowska-Koszko
- Department of Diagnostic Immunology, Pomeranian Medical University, st. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (P.R.); (I.W.-K.)
| | - Andrzej Dybus
- Department of Genetics, West Pomeranian University of Technology, st. Aleja Piastów 45, 70-311 Szczecin, Poland; (A.R.); (A.D.)
| | - Yeong-Hsiang Cheng
- Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; (Y.-H.C.); (Y.-H.Y.)
| | - Yu-Hsiang Yu
- Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; (Y.-H.C.); (Y.-H.Y.)
| | - Szymon Mazgaj
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
| | - Beata Hukowska-Szematowicz
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
- Molecular Biology and Biotechnology Center, University of Szczecin, st. Wąska 13, 71-412 Szczecin, Poland
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7
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Mantzios PG, Spyropoulou P, Hatzianastasiou S, Efthymiou D, Filippopoulos E, Mamarelis C, Potsios C, Filioti K, Letsas CA. Pediococcus pentosaceus Endocarditis in a Patient With Recent Transcatheter Aortic Valve Implantation and Liver Cirrhosis: A Case Report and Review of the Literature. Cureus 2024; 16:e57509. [PMID: 38707070 PMCID: PMC11067400 DOI: 10.7759/cureus.57509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/03/2024] [Indexed: 05/07/2024] Open
Abstract
Transcatheter aortic valve implantation (TAVI) is increasingly being used in the management of severe aortic stenosis, mainly in older and/or medically compromised patients, due to its minimally invasive nature. As in any valve replacement procedure, endocarditis is a recognized complication, more so in TAVI patients, in whom comorbidities are highly prevalent. We report the case of a 70-year-old male with a history of liver cirrhosis and a recent TAVI, who presented with recurrent fever and sustainedPediococcus pentosaceus bacteremia. The diagnosis of endocarditis was delayed, as the microorganism was initially discarded as a contaminant, given that Pediococci are rarely described as human pathogens. However, in cirrhotic patients, microbiota may cause intermittent bacteremia and thereby affect prosthetic valves. Transthoracic echocardiography was not helpful in validating the diagnosis, as is often the case in TAVI patients. Transesophageal echocardiography was deemed perilous, due to esophageal varices complicating the underlying cirrhosis. Therefore, endocarditis diagnosis was based on sustained bacteremia and Duke's criteria, including the presence of high fever, a predisposing cardiac lesion, splenic infarction, and the exclusion of an alternative diagnosis. Moreover, cirrhosis enhanced the side effects of treatment and led to the need for regimen changes and prolonged hospitalization. Given the precariousness of the situation, confirmation of treatment success by 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography-computed tomography (18F-FDG PET-CT) scan was sought. This is the first reported case of Pediococcus TAVI endocarditis in a cirrhotic patient, highlighting the unique challenges in the diagnosis and management of TAVI endocarditis in patients with co-existing conditions.
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Efremova I, Maslennikov R, Medvedev O, Kudryavtseva A, Avdeeva A, Krasnov G, Romanikhin F, Diatroptov M, Fedorova M, Poluektova E, Levshina A, Ivashkin V. Gut Microbiota and Biomarkers of Intestinal Barrier Damage in Cirrhosis. Microorganisms 2024; 12:463. [PMID: 38543514 PMCID: PMC10972037 DOI: 10.3390/microorganisms12030463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 02/20/2024] [Accepted: 02/23/2024] [Indexed: 07/26/2024] Open
Abstract
Gut dysbiosis and subclinical intestinal damage are common in cirrhosis. The aim of this study was to examine the association of intestinal damage biomarkers (diamine oxidase [DAO], claudin 3, and intestinal fatty acid binding protein [I-FABP; FABP2]) with the state of the gut microbiota in cirrhosis. The blood levels of DAO were inversely correlated with blood levels of claudin 3, lipopolysaccharide (LPS), presepsin, TNF-α, and the severity of cirrhosis according to Child-Pugh scores. The blood level of I-FABP was directly correlated with the blood level of claudin 3 but not with that of DAO. Patients with small intestinal bacterial overgrowth (SIBO) had lower DAO levels than patients without SIBO. There was no significant difference in claudin 3 levels and I-FABP detection rates between patients with and without SIBO. The DAO level was directly correlated with the abundance of Akkermansiaceae, Akkermansia, Allisonella, Clostridiaceae, Dialister, Lactobacillus, Muribaculaceae, Negativibacillus, Ruminococcus, Thiomicrospiraceae, Verrucomicrobiae, and Verrucomicrobiota; and it was inversely correlated with the abundance of Anaerostipes, Erysipelatoclostridium, and Vibrio. The I-FABP level was directly correlated with Anaerostipes, Bacteroidia, Bacteroidota, Bilophila, Megamonas, and Selenomonadaceae; and it was inversely correlated with the abundance of Brucella, Pseudomonadaceae, Pseudomonas, and Vibrionaceae. The claudin 3 level was directly correlated with Anaerostipes abundance and was inversely correlated with the abundance of Brucella, Coriobacteriia, Eggerthellaceae, and Lactobacillus.
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Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia; (I.E.); (E.P.); (A.L.)
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia; (I.E.); (E.P.); (A.L.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119435, Russia
| | - Oleg Medvedev
- Pharmacology Department, Lomonosov Moscow State University, Leninskie Gori 1, Moscow 119991, Russia
| | - Anna Kudryavtseva
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str. 32, Moscow 119991, Russia (M.F.)
| | - Anastasia Avdeeva
- V.A. Nasonova Research Institute of Rheumatology, Kashirskoye Shose 34A, Moscow 115522, Russia; (A.A.)
| | - George Krasnov
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str. 32, Moscow 119991, Russia (M.F.)
| | - Filipp Romanikhin
- Pharmacology Department, Lomonosov Moscow State University, Leninskie Gori 1, Moscow 119991, Russia
| | - Mikhail Diatroptov
- V.A. Nasonova Research Institute of Rheumatology, Kashirskoye Shose 34A, Moscow 115522, Russia; (A.A.)
| | - Maria Fedorova
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str. 32, Moscow 119991, Russia (M.F.)
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia; (I.E.); (E.P.); (A.L.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119435, Russia
| | - Anna Levshina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia; (I.E.); (E.P.); (A.L.)
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119991, Russia; (I.E.); (E.P.); (A.L.)
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Ivashkin VT, Fomin VV, Tkacheva ON, Medvedev OS, Poluektova EA, Abdulganieva DI, Abdulkhakov SR, Alexeeva OP, Alekseenko SA, Andreev DN, Baranovsky AY, Zharkova MS, Zolnikova OY, Ivashkin KV, Kliaritskaia IL, Korochanskaya NV, Mammaev SN, Maslennikov RV, Myazin RG, Perekalina MV, Povtoreyko AV, Ulyanin AI, Fadeeva MV, Khlynov IB, Tsukanov VV, Shifrin OS. Small Intestinal Bacterial Overgrowth in Various Specialties of Medical Practice (Literature Review and Expert Council Resolution). RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2024; 34:14-34. [DOI: 10.22416/1382-4376-2024-954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
Aim: to discuss current views on the clinical significance, diagnostic opportunities, and therapeutic approaches in the treatment of small intestinal bacterial overgrowth (SIBO) as an important component in the gut microbiota function assessment, to assess the awareness of physicians and the opportunities in the diagnosis and treatment of this disease in patients in the Federal districts of the Russian Federation, as well as to present the proceedings of the Expert Council held on December 16, 2023 in Moscow.Key points. SIBO is a common syndrome often associated with irritable bowel syndrome, liver cirrhosis, asthma, and congestive heart failure, being also a predictor of early death in the elderly. Today, in many regions of the Russian Federation, there are limitations for instrumental diagnosis of this disease — lack of awareness among doctors, unavailability of gas analyzers for diagnosing SIBO, lack of information about the need to diagnose SIBO in the standards of compulsory health insurance. Rifaximin is the first-line treatment due to the highest therapeutic efficacy. One of the ways to increase the efficacy of SIBO treatment is to include strain-specific probiotics in the treatment regimen. Saccharomyces boulardii CNCM I-745 is thought to be the most studied, promising probiotic. The review also presents statistical data on the issues in the diagnosis and treatment of SIBO in the regions of the Russian Federation.Conclusion. Optimization of approaches to the diagnosis and treatment of SIBO, the development of domestic gas analyzers, increasing the awareness of physicians in all regions of the Russian Federation, as well as the development and optimization of clinical recommendations appear to be necessary measures to increase the effectiveness of medical care, the duration and quality of life of the Russian population. These goals can be achieved within the framework of Federal programs under the supervision of specialized reference centers of the Ministry of Health of the Russian Federation.
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Affiliation(s)
- V. T. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - V. V. Fomin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - O. N. Tkacheva
- N.I. Pirogov Russian National Research Medical University
| | - O. S. Medvedev
- M.V. Lomonosov Moscow State University; National Medical Research Center of Cardiology names after Academician E.I. Chazov
| | - E. A. Poluektova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - S. R. Abdulkhakov
- Kazan State Medical University; Kazan (Volga Region) Federal University
| | | | | | | | | | - M. S. Zharkova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - O. Yu. Zolnikova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. V. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | - R. V. Maslennikov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | - A. I. Ulyanin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - M. V. Fadeeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - V. V. Tsukanov
- Scientific Research Institute of Medical Problems of the North, Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”
| | - O. S. Shifrin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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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; 13:919. [PMID: 38337613 PMCID: PMC10856456 DOI: 10.3390/jcm13030919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 01/26/2024] [Accepted: 01/29/2024] [Indexed: 02/12/2024] Open
Abstract
(1) 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. (2) Methods: This was a blinded, randomized, placebo-controlled study. (3) 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). (4) Conclusions: SIBO eradication was an independent predictor of a favorable prognosis during the first year of follow-up.
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Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119435, Russia
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119435, Russia
| | - Nona Benuni
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
| | - Aleksandr Kotusov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
| | - Tatyana Demina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
| | - Aleksandra Ivleva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
| | - Farida Adzhieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
| | - Taisiya Krylova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119992, Russia (M.Z.); (E.P.); (N.B.); (A.K.); (A.I.); (T.K.)
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11
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Gala KS, Winrich E, Jha SK, Parthasarathy R, Vatsalya V. Alcohol Use Disorder and the Gut Microbiome. CURRENT ADDICTION REPORTS 2023; 11:105-112. [DOI: 10.1007/s40429-023-00527-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/30/2023] [Indexed: 01/04/2025]
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12
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Liao L, Su BB, Xu SP. Helicobacter pylori infection and small intestinal bacterial overgrowth: a systematic review and meta-analysis. BMC Microbiol 2023; 23:386. [PMID: 38053022 PMCID: PMC10698970 DOI: 10.1186/s12866-023-03063-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 10/14/2023] [Indexed: 12/07/2023] Open
Abstract
BACKGROUND There is a link between Helicobacter pylori (HP) infection and small intestinal bacterial overgrowth (SIBO) with nonspecific digestive symptoms. Nonetheless, whether HP infection is associated with SIBO in adults remains unclear. Based on a meta-analysis, we evaluated this relationship. RESULTS Observational studies relevant to our research were identified by searching PubMed, Embase, the Cochrane Library, and the Web of Science. We evaluated between-study heterogeneity using the Cochrane Q test and estimated the I2 statistic. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used. Ten datasets from eight studies, including 874 patients, were involved in the meta-analysis. It was shown that HP infection was related to a higher odds of SIBO (odds ratio [OR]: 1.82, 95% confidence interval: 1.29 to 2.58, p < 0.001) with mild heterogeneity (p for Cochrane Q test = 0.11, I2 = 7%). Subgroup analyses showed that HP infection was related to SIBO in young patients (mean age < 48 years, OR: 2.68, 95% CI: 1.67 to 4.28, p < 0.001; I2 = 15%) but not in older patients (mean age ≥ 48 years, OR: 1.15, 95% CI: 0.69 to 1.92, p < 0.60; I2 = 1%; p for subgroup difference = 0.02). Subgroup analyses further indicated that the association was not significantly affected by the country of study, comorbidities, exposure to proton pump inhibitors, or methods of evaluating HP infection and SIBO. CONCLUSIONS HP infection may be related to SIBO in adults, which supports the detection of SIBO in patients with digestive symptoms and HP infection.
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Affiliation(s)
- Liang Liao
- Department of Gastroenterology, The Second Medical Center of PLA General Hospital, No.28 Fuxing Road, Beijing, 100853, China
| | - Bin-Bin Su
- Department of Gastroenterology, The Second Medical Center of PLA General Hospital, No.28 Fuxing Road, Beijing, 100853, China
| | - Shi-Ping Xu
- Department of Gastroenterology, The Second Medical Center of PLA General Hospital, No.28 Fuxing Road, Beijing, 100853, China.
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13
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Maslennikov R, Poluektova E, Zolnikova O, Sedova A, Kurbatova A, Shulpekova Y, Dzhakhaya N, Kardasheva S, Nadinskaia M, Bueverova E, Nechaev V, Karchevskaya A, Ivashkin V. Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis. Int J Mol Sci 2023; 24:16502. [PMID: 38003692 PMCID: PMC10671141 DOI: 10.3390/ijms242216502] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/11/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open
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.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119048 Moscow, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119048 Moscow, Russia
| | - Oxana Zolnikova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Alla Sedova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Anastasia Kurbatova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Yulia Shulpekova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Natyia Dzhakhaya
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Svetlana Kardasheva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Maria Nadinskaia
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Elena Bueverova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Vladimir Nechaev
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Anna Karchevskaya
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119048 Moscow, Russia
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14
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Efremova I, Maslennikov R, Poluektova E, Zharkova M, Kudryavtseva A, Krasnov G, Fedorova M, Shirokova E, Kozlov E, Levshina A, Ivashkin V. Gut Dysbiosis and Hemodynamic Changes as Links of the Pathogenesis of Complications of Cirrhosis. Microorganisms 2023; 11:2202. [PMID: 37764046 PMCID: PMC10537778 DOI: 10.3390/microorganisms11092202] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 08/26/2023] [Accepted: 08/29/2023] [Indexed: 09/29/2023] Open
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.
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Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119991 Moscow, Russia (E.P.); (M.Z.); (A.L.); (V.I.)
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119991 Moscow, Russia (E.P.); (M.Z.); (A.L.); (V.I.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119991 Moscow, Russia
- Consultative and Diagnostic Center No. 2, Moscow Health Department, 107564 Moscow, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119991 Moscow, Russia (E.P.); (M.Z.); (A.L.); (V.I.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119991 Moscow, Russia
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119991 Moscow, Russia (E.P.); (M.Z.); (A.L.); (V.I.)
| | - Anna Kudryavtseva
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology of Russian Academy of Sciences, 119991 Moscow, Russia (G.K.); (M.F.)
| | - George Krasnov
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology of Russian Academy of Sciences, 119991 Moscow, Russia (G.K.); (M.F.)
| | - Maria Fedorova
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology of Russian Academy of Sciences, 119991 Moscow, Russia (G.K.); (M.F.)
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119991 Moscow, Russia (E.P.); (M.Z.); (A.L.); (V.I.)
| | - Evgenii Kozlov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, 119991 Moscow, Russia;
| | - Anna Levshina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119991 Moscow, Russia (E.P.); (M.Z.); (A.L.); (V.I.)
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, 119991 Moscow, Russia;
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119991 Moscow, Russia (E.P.); (M.Z.); (A.L.); (V.I.)
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15
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Maslennikov R, Alieva A, Poluektova E, Zharikov Y, Suslov A, Letyagina Y, Vasileva E, Levshina A, Kozlov E, Ivashkin V. Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota. World J Gastroenterol 2023; 29:4236-4251. [PMID: 37545638 PMCID: PMC10401661 DOI: 10.3748/wjg.v29.i27.4236] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/25/2023] [Accepted: 06/21/2023] [Indexed: 07/13/2023] Open
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.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Aliya Alieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Yury Zharikov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Andrey Suslov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Yana Letyagina
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Ekaterina Vasileva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Anna Levshina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Evgenii Kozlov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
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16
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Weiler N, Bojunga J. Ernährung bei fortgeschrittener Leberzirrhose und perioperativ bei Lebertransplantation. DIE GASTROENTEROLOGIE 2023; 18:308-316. [DOI: 10.1007/s11377-023-00706-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/16/2023] [Indexed: 01/04/2025]
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17
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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; 29:3400-3421. [PMID: 37389240 PMCID: PMC10303511 DOI: 10.3748/wjg.v29.i22.3400] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 03/31/2023] [Accepted: 05/11/2023] [Indexed: 06/06/2023] Open
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.
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Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Ekaterina Vasilieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Yury Zharikov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 125009, Russia
| | - Andrey Suslov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 125009, Russia
| | - Yana Letyagina
- N.V. Sklifosovsky Institute of Clinical Medicine, Sechenov University, Moscow 119991, Russia
| | - Evgenii Kozlov
- Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Anna Levshina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
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Shah A, Ghoshal UC, Holtmann GJ. Unravelling the controversy with small intestinal bacterial overgrowth. Curr Opin Gastroenterol 2023; 39:211-218. [PMID: 37144539 DOI: 10.1097/mog.0000000000000928] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
PURPOSE OF REVIEW The aim of this review is to summarize the current and emergent approaches to characterize the small intestinal microbiota and discuss the treatment options for management of small intestinal bacterial overgrowth (SIBO). RECENT FINDINGS This review captures the growing body of evidence for the role of SIBO, a type of small intestinal dysbiosis in the pathophysiology various gastrointestinal and extraintestinal disorders. We have highlighted the drawbacks of the available methods for characterizing the small intestinal microbiota and focus on the new culture-independent techniques to diagnose SIBO. Although recurrence is common, targeted modulation of the gut microbiome as a therapeutic option for management of SIBO is associated with improvement in symptoms and quality of life. SUMMARY As a first step to precisely characterize the potential link between SIBO and various disorders, we need to address the methodological limitations of the available traditional tests for diagnosing SIBO. There is an urgency to develop culture independent techniques that can be routinely used in clinical setting, that will enable characterization of the gastrointestinal microbiome and explore the response to antimicrobial therapy including the links between long-lasting symptom resolution and the microbiome.
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Affiliation(s)
- Ayesha Shah
- The University of Queensland, Faculty of Medicine and Faculty of Health and Behavioural Sciences
- Princess Alexandra Hospital, Department of Gastroenterology & Hepatology, Brisbane, QLD, Australia
| | - Uday C Ghoshal
- Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Gerald J Holtmann
- The University of Queensland, Faculty of Medicine and Faculty of Health and Behavioural Sciences
- Princess Alexandra Hospital, Department of Gastroenterology & Hepatology, Brisbane, QLD, Australia
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Efremova I, Maslennikov R, Alieva A, Poluektova E, Ivashkin V. Small Intestinal Bacterial Overgrowth Is Associated with Poor Prognosis in Cirrhosis. Microorganisms 2023; 11:1017. [PMID: 37110440 PMCID: PMC10143588 DOI: 10.3390/microorganisms11041017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/03/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
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.
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Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119121 Moscow, Russia
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119121 Moscow, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119121 Moscow, Russia
| | - Aliya Alieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119121 Moscow, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119121 Moscow, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119121 Moscow, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119121 Moscow, Russia
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20
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Kossewska J, Bierlit K, Trajkovski V. Personality, Anxiety, and Stress in Patients with Small Intestine Bacterial Overgrowth Syndrome. The Polish Preliminary Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 20:93. [PMID: 36612414 PMCID: PMC9819554 DOI: 10.3390/ijerph20010093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 12/19/2022] [Accepted: 12/20/2022] [Indexed: 06/17/2023]
Abstract
OBJECTIVE Small intestinal bacterial overgrowth (SIBO) syndrome is associated with depression and anxiety. This study aimed to examine for the first time the correlation between personality traits, situational anxiety, and stress in Polish patients with SIBO. METHODOLOGY This study included 26 patients with SIBO aged 20-35 years and 24 non-SIBO patients aged 20-35 years. The following instruments were used: NEO-FFI Personality Inventory, KPS Sense of Stress Questionnaire, and the anxiety-state subscale from the State-Trait Anxiety Inventory (STAI). RESULTS Compared to the non-SIBO subgroup, SIBO patients expressed specific patterns of personality traits: higher neuroticism, lower extroversion, and a higher state of anxiety and stress. Unlike the non-SIBO subgroup, stress (total emotional tension, external, and intrapsychic) correlated negatively only with extroversion. CONCLUSIONS Personality is the primary regulator of experience and behavior. The specificity captured in the research is a premise for an in-depth study considering various psychological variables to determine cause-effect relationships.
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Affiliation(s)
- Joanna Kossewska
- Institute of Special Education, School Education and Teachers Education, Pedagogical University of Krakow, 30-084 Kraków, Poland
| | - Karolina Bierlit
- Student Scientific Club of Supporting People with Autism, Pedagogical University of Krakow, 30-084 Kraków, Poland
| | - Vladimir Trajkovski
- Macedonian Scientific Society for Autism, Institute of Special Education and Rehabilitation, Faculty of Philosophy, Ss. Cyril & Methodius University in Skopje, 1000 Skopje, North Macedonia
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21
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Hepatic Encephalopathy in Cirrhotic Patients and Risk of Small Intestinal Bacterial Overgrowth: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:2469513. [PMID: 36303585 PMCID: PMC9596239 DOI: 10.1155/2022/2469513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 10/04/2022] [Accepted: 10/05/2022] [Indexed: 11/23/2022]
Abstract
Background Hepatic encephalopathy (HE) is a neurological and psychiatric syndrome. Recent evidence suggests that HE is not only a disease of the liver and brain but is also related to the gut. Small intestinal bacterial overgrowth (SIBO) is well known to be associated with cirrhosis, but the relationship between SIBO and HE is unclear. We conducted this comprehensive systematic review and meta-analysis to determine the association between SIBO and HE in cirrhotic patients. Methods We conducted a comprehensive literature search of all studies on the association of SIBO and HE in cirrhotic patients using the PubMed and Embase electronic databases. Studies were screened, and relevant data were extracted and analysed. We calculated the number of cases of SIBO in patients with HE and controls. We then compared the prevalence of SIBO between the two groups to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Funnel plots were constructed to identify potential publication bias. Results Six studies with 414 participants (219 HE patients and 195 controls) met the inclusion criteria. The prevalence of SIBO in cirrhotic patients with HE was significantly higher than that in those without HE. The combined OR was 4.43 (95% CI 1.73-11.32, P = 0.002). The heterogeneity was moderate (I2 = 66%), and the funnel plot suggested no significant publication bias. Subgroup analysis showed that the OR was 1.95 (95% CI 0.63–6.09) in studies using the lactulose breath test (LBT) and 7.60 (95% CI 3.50–16.50) in studies using the glucose breath test (GBT). The prevalence of SIBO in cirrhotic patients was also related to the severity of liver disease. Conclusions Our meta-analysis identified a strong association between SIBO and HE, and the risk of SIBO was 4.43 times higher among cirrhotic patients with HE than among those without HE. SIBO could be a predisposing factor for the development of HE in cirrhotic patients. Therefore, the importance of SIBO should be emphasized in patients with HE.
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22
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Chang C, Yuan X, Zhang X, Chen X, Li K. Gastrointestinal Microbiome and Multiple Health Outcomes: Umbrella Review. Nutrients 2022; 14:3726. [PMID: 36145102 PMCID: PMC9505003 DOI: 10.3390/nu14183726] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 08/29/2022] [Accepted: 09/08/2022] [Indexed: 11/22/2022] Open
Abstract
In recent years, there has been growing concern about the impact of the gastrointestinal microbiome on human health outcomes. To clarify the evidence for a link between the gastrointestinal microbiome and a variety of health outcomes in humans, we conducted an all-encompassing review of meta-analyses and systematic reviews that included 195 meta-analyses containing 950 unique health outcomes. The gastrointestinal microbiome is related to mortality, gastrointestinal disease, immune and metabolic outcomes, neurological and psychiatric outcomes, maternal and infant outcomes, and other outcomes. Existing interventions for intestinal microbiota (such as probiotics, fecal microbiota transplant, etc.) are generally safe and beneficial to a variety of human health outcomes, but the quality of evidence is not high, and more detailed and well-designed randomized controlled trials are necessary.
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Affiliation(s)
- Chengting Chang
- West China School of Nursing, Sichuan University/West China Hospital, Sichuan University, 37 Guo Xue Rd., Chengdu 610041, China
| | - Xingzhu Yuan
- West China School of Nursing, Sichuan University/West China Hospital, Sichuan University, 37 Guo Xue Rd., Chengdu 610041, China
| | - Xingxia Zhang
- Department of Organization, West China Hospital, Sichuan University, 37 Guo Xue Rd., Chengdu 610041, China
| | - Xinrong Chen
- West China School of Nursing, Sichuan University/West China Hospital, Sichuan University, 37 Guo Xue Rd., Chengdu 610041, China
| | - Ka Li
- West China School of Nursing, Sichuan University/West China Hospital, Sichuan University, 37 Guo Xue Rd., Chengdu 610041, China
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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; 14:1667-1677. [PMID: 36157871 PMCID: PMC9453455 DOI: 10.4254/wjh.v14.i8.1667] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/12/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
- Consultative and Diagnostic Center No. 2 of Moscow Health Department , Moscow 107764, Russia.
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Konstantin Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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Ivashkin VT, Maev IV, Abdulganieva DI, Alekseeva OP, Alekseenko SA, Zolnikova OY, Korochanskaya NV, Medvedev OS, Poluektova EA, Simanenkov VI, Trukhmanov AS, Khlynov IB, Tsukanov VV, Shifrin OS, Ivashkin KV, Lapina TL, Maslennikov RV, Fadeeva MV, Ulyanin AI. 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; 32:68-85. [DOI: 10.22416/1382-4376-2022-32-3-68-85] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
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.
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Affiliation(s)
- V. T. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - I. V. Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | - O. Yu. Zolnikova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - O. S. Medvedev
- Lomonosov Moscow State University;
Institute of Experimental Cardiology of National Medical Research Center of Cardiology
| | - E. A. Poluektova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - A. S. Trukhmanov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - V. V. Tsukanov
- Research Institute for Medical Problems in the North — Division of Krasnoyarsk Scientific Centre of the Siberian Branch of the RAS
| | - O. S. Shifrin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. V. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - T. L. Lapina
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - R. V. Maslennikov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - M. V. Fadeeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. I. Ulyanin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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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; 14:1210-1225. [PMID: 35978666 PMCID: PMC9258262 DOI: 10.4254/wjh.v14.i6.1210] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 07/09/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
- Department of Internal Medicine, Сonsultative and Diagnostic Center No. 2, Moscow City Health Department, Moscow 107564, Russia.
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Aliya Alieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Anna Kudryavtseva
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
- Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
| | - George Krasnov
- Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Yuri Zharikov
- Department of Anatomy, Sechenov University, Moscow 119435, Russia
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Scarpellini E, Abenavoli L, Cassano V, Rinninella E, Sorge M, Capretti F, Rasetti C, Svegliati Baroni G, Luzza F, Santori P, Sciacqua A. The Apparent Asymmetrical Relationship Between Small Bowel Bacterial Overgrowth, Endotoxemia, and Liver Steatosis and Fibrosis in Cirrhotic and Non-Cirrhotic Patients: A Single-Center Pilot Study. Front Med (Lausanne) 2022; 9:872428. [PMID: 35559337 PMCID: PMC9090439 DOI: 10.3389/fmed.2022.872428] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 03/18/2022] [Indexed: 11/18/2022] Open
Abstract
Introduction Gut microbiota are a complex ecosystem harboring our intestine. They maintain human body equilibrium, while their derangement, namely, “dysbiosis“, has been associated with several gastrointestinal diseases, such as liver steatosis (NAFLD) and liver cirrhosis. Small intestinal bacterial overgrowth (SIBO) is an example of dysbiosis of the upper gastrointestinal (GI) tract. Aim The aim of this study is to evaluate the relationship between SIBO and levels of endotoxemia and grade of liver steatosis (LS) and liver fibrosis (LF) in hepatologic patients. Materials and Methods Consecutive outpatients referred to our hepatology clinic were tested for SIBO by the lactulose breath test (LBT) and peripheral blood levels of endotoxemia; LS grading and LF were assessed by abdominal ultrasound and transient elastography, respectively. Results Fifty-two consecutive patients (17 with alcohol abuse (4.5 ± 0.8 alcohol units per day), 4 with HCV and 2 with HBV infection, 24 of metabolic origin, 2 of autoimmune origin, and 3 with cholangiopathies; mean age 54.7 ± 8.3 years, 31 F, BMI 24.1 ± 1.1 Kg/m2) and 14 healthy volunteers (HV) (mean age 50.1 ± 4.3 years, 9 F, BMI 23.3 ± 1.1 Kg/m2) were enrolled. SIBO prevalence was significantly higher in cirrhotic (LC) vs. non-cirrhotic (LNC) patients and vs. HV (all, p < 0.05), with a significant positive trend according to Child-Pugh status (all, p < 0.05). SIBO prevalence was not correlated with LS stages (all, p = NS). Consensually, endotoxin levels were significantly higher in LC vs. LNC and vs. HV (all, p < 0.05) and significantly correlated with LF in patients with LC, according to Child-Pugh status (all, p < 0.05). Conclusion This study shows that SIBO prevalence and relative endotoxin blood levels seem to be significantly associated with the grade of LF vs. LS in LC. SIBO is also present under pre-cirrhotic conditions, but its prevalence seems to correlate with liver disease irreversible derangement.
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Affiliation(s)
- E. Scarpellini
- Hepatology and Internal Medicine Unit, “Madonna del Soccorso” General Hospital, San Benedetto del Tronto, Italy
- T.A.R.G.I.D., Gasthuisberg University Hospital, KULeuven, Lueven, Belgium
- *Correspondence: E. Scarpellini
| | - L. Abenavoli
- Department of Health Sciences, University “Magna Græcia”, Catanzaro, Italy
| | - V. Cassano
- Department of Medical and Surgical Sciences, University “Magna Græcia”, Catanzaro, Italy
| | - E. Rinninella
- Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - M. Sorge
- Gastroenterology and Endoscopy Unit “Madonna del Soccorso” General Hospital, San Benedetto del Tronto, Italy
| | - F. Capretti
- Gastroenterology and Endoscopy Unit “Madonna del Soccorso” General Hospital, San Benedetto del Tronto, Italy
| | - C. Rasetti
- Hepatology and Internal Medicine Unit, “Madonna del Soccorso” General Hospital, San Benedetto del Tronto, Italy
| | - G. Svegliati Baroni
- Gastroenterology Clinic, “Riuniti University Hospital”, Polytechnics University of Marche, Ancona, Italy
| | - F. Luzza
- Department of Health Sciences, University “Magna Græcia”, Catanzaro, Italy
| | - P. Santori
- Hepatology and Internal Medicine Unit, “Madonna del Soccorso” General Hospital, San Benedetto del Tronto, Italy
| | - A. Sciacqua
- Department of Medical and Surgical Sciences, University “Magna Græcia”, Catanzaro, Italy
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Tranah TH, Kronsten VT, Shawcross DL. Implications and Management of Cirrhosis-Associated Immune Dysfunction Before and After Liver Transplantation. Liver Transpl 2022; 28:700-716. [PMID: 34738724 DOI: 10.1002/lt.26353] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/18/2021] [Accepted: 10/27/2021] [Indexed: 12/28/2022]
Abstract
Cirrhosis-associated immune dysfunction (CAID) describes a panacea of innate and adaptive deficits that result from the sequelae of cirrhotic portal hypertension that is similar in its manifestations regardless of etiology of chronic liver injury. CAID is associated with synchronous observations of dysregulated priming of innate immune effector cells that demonstrate a proinflammatory phenotype but are functionally impaired and unable to adequately prevent invading pathogens. CAID is mainly driven by gut-barrier dysfunction and is associated with deficits of microbial compartmentalization and homeostasis that lead to tonic activation, systemic inflammation, and exhaustion of innate-immune cells. CAID leads to a high frequency of bacterial and fungal infections in patients with cirrhosis that are often associated with acute decompensation of chronic liver disease and acute-on-chronic liver failure and carry a high mortality rate. Understanding the deficits of mucosal and systemic immunity in the context of chronic liver disease is essential to improving care for patients with cirrhosis, preventing precipitants of acute decompensation of cirrhosis, and improving morbidity and survival. In this review, we summarize the detailed dynamic immunological perturbations associated with advanced chronic liver disease and highlight the importance of recognizing immune dysregulation as a sequela of cirrhosis. Furthermore, we address the role of screening, prevention, and early treatment of infections in cirrhosis in improving patient outcomes in transplant and nontransplant settings.
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Affiliation(s)
- Thomas H Tranah
- Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.,Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, UK
| | - Victoria T Kronsten
- Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.,Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, UK
| | - Debbie L Shawcross
- Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.,Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, UK
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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; 28:1067-1077. [PMID: 35431497 PMCID: PMC8968519 DOI: 10.3748/wjg.v28.i10.1067] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/29/2021] [Accepted: 02/09/2022] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
- Department of Internal Medicine 1, Сonsultative and Diagnostic Center 2 of the Moscow City Health Department, Moscow 107564, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Anna Kudryavtseva
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - George Krasnov
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
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Yokoyama K, Sakamaki A, Takahashi K, Naruse T, Sato C, Kawata Y, Tominaga K, Abe H, Sato H, Tsuchiya A, Kamimura K, Takamura M, Yokoyama J, Terai S. Hydrogen-producing small intestinal bacterial overgrowth is associated with hepatic encephalopathy and liver function. PLoS One 2022; 17:e0264459. [PMID: 35213654 PMCID: PMC8880851 DOI: 10.1371/journal.pone.0264459] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 02/11/2022] [Indexed: 12/15/2022] Open
Abstract
Overt hepatic encephalopathy (HE) is one of the complications of liver cirrhosis (LC), which negatively affects the prognosis and quality of life of patients. Small intestinal bacterial overgrowth (SIBO) is significantly associated with LC and its complications, including HE. We investigated the relationship between SIBO and LC, and the difference between hydrogen-producing and methane-producing SIBO (H-SIBO and M-SIBO, respectively). This is a prospective cohort study of 107 cases. Breath measurements of hydrogen and methane concentrations were performed for the diagnosis of SIBO. The study cohort included 81 males with a median age of 70 (40-86) years, and SIBO was detected in 31 cases (29.0%). There were no significant differences between the SIBO positive and SIBO negative groups. Reclassification into H-SIBO (16 cases) and others (91 cases) was performed, and the Child-Pugh score was only derived in the multivariate logistic analysis (P = 0.028, odds ratio 1.39, 95% confidence interval 1.04-1.85). Furthermore, H-SIBO was significantly associated with covert HE in chi-square test (50.0% vs. 24.2%, P = 0.034). In addition, we evaluated the therapeutic response on SIBO of rifaximin in eight covert HE patients. 20% patients with M-SIBO and 67% patients with H-SIBO showed an improvement of the breath test. In conclusion, H-SIBO, but not M-SIBO, is significantly associated with liver function, and rifaximin might be more effective for covert HE with H-SIBO. Therefore, the diagnosis of SIBO, including the classification as H-SIBO and M-SIBO, might help to determine the choice of treatment for HE.
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Affiliation(s)
- Kunihiko Yokoyama
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kazuya Takahashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takumi Naruse
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Chihiro Sato
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yuzo Kawata
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kentaro Tominaga
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroyuki Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroki Sato
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Department of General Medicine, School of Medicine, Niigata University, Niigata, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Junji Yokoyama
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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Ghoshal UC, Sachdeva S, Ghoshal U, Misra A, Puri AS, Pratap N, Shah A, Rahman MM, Gwee KA, Tan VPY, Ahmed T, Lee YY, Ramakrishna BS, Talukdar R, Rana SV, Sinha SK, Chen M, Kim N, Holtmann G. Asian-Pacific consensus on small intestinal bacterial overgrowth in gastrointestinal disorders: An initiative of the Indian Neurogastroenterology and Motility Association. Indian J Gastroenterol 2022; 41:483-507. [PMID: 36214973 PMCID: PMC9549446 DOI: 10.1007/s12664-022-01292-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 08/02/2022] [Indexed: 02/04/2023]
Abstract
In the clinical setting, small intestinal bacterial overgrowth (SIBO) is a frequent, but under-diagnosed entity. SIBO is linked to various gastrointestinal (GI) and non-GI disorders with potentially significant morbidity. The optimal management of SIBO is undefined while there is a lack of published consensus guidelines. Against this background, under the auspices of the Indian Neurogastroenterology and Motility Association (INMA), formerly known as the Indian Motility and Functional Diseases Association (IMFDA), experts from the Asian-Pacific region with extensive research and clinical experience in the field of gut dysbiosis including SIBO developed this evidence-based practice guideline for the management of SIBO utilizing a modified Delphi process based upon 37 consensus statements, involving an electronic voting process as well as face-to-face meetings and review of relevant supporting literature. These statements include 6 statements on definition and epidemiology; 11 on etiopathogenesis and pathophysiology; 5 on clinical manifestations, differential diagnosis, and predictors; and 15 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservations was 80% or higher, the statement was regarded as accepted. The members of the consensus team consider that this guideline would be valuable to inform clinical practice, teaching, and research on SIBO in the Asian-Pacific region as well as in other countries.
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Affiliation(s)
- Uday C. Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014 India
| | - Sanjeev Sachdeva
- Department of Gastroenterology, G B Pant Hospital, New Delhi, 110 002 India
| | - Ujjala Ghoshal
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014 India
| | - Asha Misra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014 India
| | | | | | - Ayesha Shah
- University of Queensland, Faculty of Medicine, and Princess Alexandra Hospital, Department of Gastroenterology and Hepatology, Brisbane, Queensland, Australia
| | - M. Masudur Rahman
- Sheikh Russel National Gastroliver Institute and Hospital, Dhaka, Bangladesh
| | - Kok Ann Gwee
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ,Stomach, Liver and Bowel Centre, Gleneagles Hospital, Singapore, Singapore
| | - Victoria P Y Tan
- Faculty of Medicine, University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Tahmeed Ahmed
- International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia ,GI Function and Motility Unit, Hospital Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - B S Ramakrishna
- SIMS Institute of Gastroenterology, Hepatology, and Transplantation, SRM Institutes for Medical Science, Chennai, 600 026 India
| | - Rupjyoti Talukdar
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, 500 082 India
| | - S V Rana
- Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, 249 203 India
| | - Saroj K Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012 India
| | - Minhu Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Gerald Holtmann
- University of Queensland, Faculty of Medicine, and Princess Alexandra Hospital, Department of Gastroenterology and Hepatology, Brisbane, Queensland, Australia
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Chaudhari A, Dwivedi MK. The concept of probiotics, prebiotics, postbiotics, synbiotics, nutribiotics, and pharmabiotics. PROBIOTICS IN THE PREVENTION AND MANAGEMENT OF HUMAN DISEASES 2022:1-11. [DOI: 10.1016/b978-0-12-823733-5.00013-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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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; 9:9320-9332. [PMID: 34877269 PMCID: PMC8610853 DOI: 10.12998/wjcc.v9.i31.9320] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 06/03/2021] [Accepted: 09/07/2021] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization "Scientific Community for the Promotion of the Clinical Study of the Human Microbiome", Moscow 119435, Russia
- Department of Internal Medicine, Consultative and Diagnostic Center of the Moscow City Health Department, Moscow 107564, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization "Scientific Community for the Promotion of the Clinical Study of the Human Microbiome", Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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Maslennikov R, Ivashkin V, Efremova I, Poluektova E, Shirokova E. Probiotics in hepatology: An update. World J Hepatol 2021; 13:1154-1166. [PMID: 34630882 PMCID: PMC8473492 DOI: 10.4254/wjh.v13.i9.1154] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 06/04/2021] [Accepted: 08/16/2021] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
- Department of Internal Medicine, Consultative and Diagnostic Center of the Moscow City Health Department, Moscow 107564, Russia.
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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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.
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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; 13:557-570. [PMID: 34131470 PMCID: PMC8173342 DOI: 10.4254/wjh.v13.i5.557] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 02/28/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119435, Russia.
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Aliya Alieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Ekaterina Kashuh
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Ekaterina Tsvetaeva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Konstantin Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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36
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Yamamoto K, Honda T, Ito T, Ishizu Y, Kuzuya T, Nakamura M, Miyahara R, Kawashima H, Ishigami M, Fujishiro M. The relationship between oral-origin bacteria in the fecal microbiome and albumin-bilirubin grade in patients with hepatitis C. J Gastroenterol Hepatol 2021; 36:790-799. [PMID: 32744764 DOI: 10.1111/jgh.15206] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 07/20/2020] [Accepted: 07/28/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Bacteria of oral origin (BO) in the gut are associated with prognosis in patients with cirrhosis. The Greengenes database (gg_13_8) is widely used in microbiome analysis, but the expanded Human Oral Microbiome Database (eHOMD), a specialized database for BO, can add more detailed information. We used each database to evaluate the relationship between the albumin-bilirubin grade (ALBI) and the microbiome in patients with hepatitis C. METHODS Eighty patients were classified into the low ALBI group (LA; n = 34) or high ALBI group (HA; n = 46). Isolated DNA from stool was amplified to target the V3-4 regions of 16S rRNA. The microbiomes of the two groups were compared using gg_13_8 or eHOMD. We evaluated the associations between microbiomes and prognoses using Cox proportional hazards models. RESULTS At the genus level, the two groups differed significantly regarding 6 (gg_13_8) and 7 (eHOMD) types of bacteria. All types except Akkermansia are classified as BO. Both databases showed an increase in Streptococcus and Veillonella. eHOMD showed a decrease in Fusobacterium and an increase in Fretibacterium; both produce various types of short-chain fatty acids. At the species level, the two groups demonstrated significant differences in 2 (gg_13_8) and 6 (eHOMD) bacterial types. Selenomonas noxia and Streptococcus salivarius were related to poor prognosis in univariate analysis. CONCLUSION The HA group demonstrated increased BO, most of which produce lactic acid or acetic acid. The correlation between the microbiome and metabolism might be related to prognosis. eHOMD was a useful database for analyzing BO.
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Affiliation(s)
- Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ryoji Miyahara
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Traub J, Reiss L, Aliwa B, Stadlbauer V. Malnutrition in Patients with Liver Cirrhosis. Nutrients 2021; 13:540. [PMID: 33562292 PMCID: PMC7915767 DOI: 10.3390/nu13020540] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 02/04/2021] [Accepted: 02/04/2021] [Indexed: 12/13/2022] Open
Abstract
Liver cirrhosis is an increasing public health threat worldwide. Malnutrition is a serious complication of cirrhosis and is associated with worse outcomes. With this review, we aim to describe the prevalence of malnutrition, pathophysiological mechanisms, diagnostic tools and therapeutic targets to treat malnutrition. Malnutrition is frequently underdiagnosed and occurs-depending on the screening methods used and patient populations studied-in 5-92% of patients. Decreased energy and protein intake, inflammation, malabsorption, altered nutrient metabolism, hypermetabolism, hormonal disturbances and gut microbiome dysbiosis can contribute to malnutrition. The stepwise diagnostic approach includes a rapid prescreen, the use of a specific screening tool, such as the Royal Free Hospital Nutritional Prioritizing Tool and a nutritional assessment by dieticians. General dietary measures-especially the timing of meals-oral nutritional supplements, micronutrient supplementation and the role of amino acids are discussed. In summary malnutrition in cirrhosis is common and needs more attention by health care professionals involved in the care of patients with cirrhosis. Screening and assessment for malnutrition should be carried out regularly in cirrhotic patients, ideally by a multidisciplinary team. Further research is needed to better clarify pathogenic mechanisms such as the role of the gut-liver-axis and to develop targeted therapeutic strategies.
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Affiliation(s)
- Julia Traub
- Department of Clinical Medical Nutrition, University Hospital Graz, 8036 Graz, Austria; (J.T.); (L.R.)
| | - Lisa Reiss
- Department of Clinical Medical Nutrition, University Hospital Graz, 8036 Graz, Austria; (J.T.); (L.R.)
| | - Benard Aliwa
- Department of Gastroenterology and Hepatology, Medical University of Graz, 8036 Graz, Austria;
| | - Vanessa Stadlbauer
- Department of Gastroenterology and Hepatology, Medical University of Graz, 8036 Graz, Austria;
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Hassouneh R, Bajaj JS. Gut Microbiota Modulation and Fecal Transplantation: An Overview on Innovative Strategies for Hepatic Encephalopathy Treatment. J Clin Med 2021; 10:330. [PMID: 33477417 PMCID: PMC7830387 DOI: 10.3390/jcm10020330] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/07/2021] [Accepted: 01/09/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatic encephalopathy (HE) is a major complication of cirrhosis, which is associated with gut microbial composition and functional alterations. Current treatments largely focus on gut microbiota using lactulose, rifaximin and other agents. However, despite these treatments, patients with HE have a high rate of readmission, morbidity and cognitive impairment. Fecal microbiota transplant (FMT) involves introduction of a donor microbiota into a recipient and is currently mainly used for recurrent C. difficile infection (rCDI). The role of FMT in cirrhosis and HE is evolving. There have been two randomized clinical trials (RCT) and several case reports/series in cirrhosis. Both RCTs were safety-focused phase 1 trials. One involved pre-FMT antibiotics and FMT enema versus standard of care, while the other involved 15 FMT capsules versus placebo without pre-FMT antibiotics. There was evidence of safety in both trials and the FMT group demonstrated reduction in hospitalizations compared to the non-FMT group. Changes in microbial function centered around short-chain fatty acids, bile acids and brain function showed improvement in the FMT groups. Long-term follow-up demonstrated continued safety and reduction in the antibiotic-resistance gene carriage. However, larger trials of FMT in HE are needed that can refine the dose, duration and route of FMT administration.
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Affiliation(s)
- Ramzi Hassouneh
- Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA;
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology and Nutrition Virginia Commonwealth University and Central Virginia Veterans Healthcare System, 1201 Broad Rock Blvd, Richmond, VA 23249, USA
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Kucheryavyy YA, Andreev DN, Maev IV. [Prevalence of small bowel bacterial overgrowth in patients with functional dyspepsia: a meta-analysis]. TERAPEVT ARKH 2020; 92:53-58. [PMID: 33720574 DOI: 10.26442/00403660.2020.12.200433] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 02/07/2021] [Indexed: 12/12/2022]
Abstract
AIM Systematization of data on the frequency of detection of the syndrome of bacterial overgrowth in the small intestine (SIBO) in patients with functional dyspepsia (FD). MATERIALS AND METHODS MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, the Russian Science Citation Index (RSCI) through July 2020 were searched to identify studies evaluating the prevalence of SIBO in FD. In addition, a search for relevant abstracts was carried out in the electronic databases of the United European Gastroenterology Week (UEG), American College of Gastroenterology (ACG), International Conference on Nutrition and Food (ICNF). For the final analysis, publications were selected that used validated tests for the assessment of SIBO (hydrogen breath test using glucose or lactulose) with detailed descriptive statistics, allowing the resulting data to be included in the meta-analysis. RESULTS The final analysis included 7 studies with 1248 patients with FD. Overall pooled prevalence of SIBO in patients with FD was 34.73% (95% CI 24.80745.383). There was significant heterogeneity between the results (p0.0001; I2=89.91%). When excluded from the meta-analysis of a study in which the incidence of SIBO was studied in patients with refractory FD, the pooled prevalence was 38.98% (95% CI 28.96449.490). CONCLUSION This meta-analysis has demonstrated that SIBO is often associated with FD and is observed in about every third patient with this functional gastrointestinal tract disease.
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Affiliation(s)
- Y A Kucheryavyy
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - D N Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
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Sarkar S, Das D, Dutta P, Kalita J, Wann SB, Manna P. Chitosan: A promising therapeutic agent and effective drug delivery system in managing diabetes mellitus. Carbohydr Polym 2020; 247:116594. [PMID: 32829787 DOI: 10.1016/j.carbpol.2020.116594] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 06/03/2020] [Accepted: 06/03/2020] [Indexed: 02/06/2023]
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Skinner C, Thompson AJ, Thursz MR, Marchesi JR, Vergis N. Intestinal permeability and bacterial translocation in patients with liver disease, focusing on alcoholic aetiology: methods of assessment and therapeutic intervention. Therap Adv Gastroenterol 2020; 13:1756284820942616. [PMID: 33149761 PMCID: PMC7580143 DOI: 10.1177/1756284820942616] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 06/25/2020] [Indexed: 02/04/2023] Open
Abstract
Increased bacterial translocation (BT) across the gut barrier due to greater intestinal permeability (IP) is seen across a range of conditions, including alcohol-related liver disease (ArLD). The phenomenon of BT may contribute to both the pathogenesis and the development of complications in ArLD. There are a number of methods available to assess IP and in this review we look at their various advantages and limitations. The knowledge around BT and IP in ArLD is also reviewed, as well as the therapeutic strategies currently in use and in development.
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Affiliation(s)
- Charlotte Skinner
- Department of Metabolism, Digestion and Reproduction, St Mary’s Hospital Campus, Imperial College London, London, UK
| | - Alex J. Thompson
- Department of Surgery & Cancer, St. Mary’s Hospital Campus, Imperial College London, London, UK
| | - Mark R. Thursz
- Department of Metabolism, Digestion and Reproduction, St Mary’s Hospital Campus, Imperial College London, London, UK
| | - Julian R. Marchesi
- Department of Metabolism, Digestion and Reproduction, St Mary’s Hospital Campus, Imperial College London, London, UK
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Small Intestinal Bacterial Overgrowth: How to Diagnose and Treat (and Then Treat Again). Gastroenterol Clin North Am 2020; 49:571-587. [PMID: 32718571 DOI: 10.1016/j.gtc.2020.04.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Small intestinal bacterial overgrowth (SIBO) is a condition with presentation that can vary from asymptomatic to steatorrhea and malnutrition. Small bowel aspiration and culture is the current gold standard of diagnosis; however, this is invasive and is not without risk to the patient. Breath testing is a noninvasive and less expensive alternative method; however, it lacks diagnostic sensitivity and specificity. Novel diagnostic methods being studied include gas-sensing capsules. The mainstay of treatment is antibiotics; alternative therapies include herbal medications, dietary modifications, and prokinetic agents. Further investigation into less invasive and less harmful diagnostic methods and treatment options is warranted.
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Sakamaki A, Yokoyama K, Yamazaki F, Kamimura H, Kamimura K, Takamura M, Yokoyama J, Terai S. Small Intestinal Bacterial Overgrowth Diagnosed by a Breath Test and Improved by Rifaximin in a Patient with Hepatic Encephalopathy and Alcoholic Liver Cirrhosis. Intern Med 2020; 59:1849-1853. [PMID: 32321898 PMCID: PMC7474984 DOI: 10.2169/internalmedicine.4593-20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 03/04/2020] [Indexed: 12/12/2022] Open
Abstract
A 66-year-old Japanese man was admitted to our hospital with grade 2 hepatic encephalopathy (HE). Abdominal computed tomography and laboratory examinations revealed decompensated liver cirrhosis. Intravenous administration of branched-chain amino acids immediately ameliorated the HE, and lactulose was initiated. However, a breath test revealed small intestinal bacterial overgrowth (SIBO); therefore, rifaximin was additionally initiated. The breath test was repeated after discharge, when no evidence of SIBO or overt HE was identified. This case suggested that a breath test is effective for the identification of SIBO and that the administration of a poorly absorbed antibiotic should be considered in SIBO-positive HE patients taking lactulose.
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Affiliation(s)
- Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
| | - Kunihiko Yokoyama
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
| | - Fusako Yamazaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
| | - Junji Yokoyama
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
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Gut Microbiota and Liver Fibrosis: One Potential Biomarker for Predicting Liver Fibrosis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3905130. [PMID: 32685479 PMCID: PMC7322594 DOI: 10.1155/2020/3905130] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 05/19/2020] [Indexed: 12/16/2022]
Abstract
Purpose To investigate the relationship between gut microbiota and liver fibrosis and establish a microbiota biomarker for detecting and staging liver fibrosis. Methods 131 Wistar rats were used in our study, and liver fibrosis was induced by carbon tetrachloride. Stool samples were collected within 72 hours after the last administration. The V4 regions of 16S rRNA gene were amplified. The sequencing data was processed using the Quantitative Insights Into Microbial Ecology (QIIME version 1.9). The diversity, principal coordinate analysis (PCoA), nonmetric multidimensional scaling (NMDS), and linear discriminant analysis (LDA) effect size (LEfSe) were performed. Random-Forest classification was performed for discriminating the samples from different groups. Microbial function was assessed using the PICRUST. Results The Simpson in the control group was lower than that in the liver fibrosis group (p = 0.048) and differed significantly among different fibrosis stages (p = 0.047). The Chao1 index in the control group was higher than that in the liver fibrosis group (p < 0.001). NMDS analysis showed a marked difference between the control and liver fibrosis groups (p < 0.001). PCoA analysis indicated the different community composition between the control and liver fibrosis groups with variances of PC1 13.76% and PC2 5.89% and between different liver fibrosis stages with variances of PC1 10.51% and PC2 7.78%. LEfSe analysis showed alteration of gut microbiota in the liver fibrosis group. Biomarkers obtained from Random-Forest classification showed excellent diagnostic accuracy in prediction of liver fibrosis with AUROCs of 0.99. The AUROCs were 0.77~0.84 in prediction of stage F4. There were six increased and 17 decreased metabolic functions in the liver fibrosis group and 6 metabolic functions significantly differed among four liver fibrosis stages. Conclusion Gut microbiota is a potential biomarker for detecting and staging liver fibrosis with high diagnostic accuracies.
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Bruns T, Stallmach A. Gastrointestinale Mikrobiota bei Leberzirrhose: pathophysiologische Veränderungen und therapeutische Interventionen. DER GASTROENTEROLOGE 2020; 15:194-200. [DOI: 10.1007/s11377-020-00436-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Macke L, Schulz C, Koletzko L, Malfertheiner P. Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract-evidence from next-generation sequencing studies. Aliment Pharmacol Ther 2020; 51:505-526. [PMID: 31990420 DOI: 10.1111/apt.15604] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Revised: 09/03/2019] [Accepted: 11/13/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are widely used to treat acid-related disorders of the upper gastrointestinal tract. However, large observational studies have raised concerns about PPI-associated adverse events. In recent years, data from next-generation sequencing studies suggested that PPIs affect the composition of the intestinal microbiota, while a balanced gut microbiome is essential for maintaining health. AIM To review the available evidence from next-generation sequencing studies on the effect of PPIs on the intestinal microbiome and to discuss possible implications of PPI-induced dysbiosis in health and disease. METHODS A systematic review was conducted following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. A PubMed query yielded 197 results. 19 publications met the prespecified eligibility criteria. RESULTS Twelve observational study cohorts with 708 PPI users and 11 interventional cohorts with 180 PPI users were included in the review. In most studies, PPI treatment did not affect microbiological richness and diversity, but was associated with distinct taxonomic alterations: In the upper gastrointestinal tract, PPI users showed overgrowth of orally derived bacteria, mostly Streptococcaceae (findings based on six independent cohorts with 126 PPI users). In faecal samples, PPIs increased multiple taxa from the orders Bacillales (eg, Staphylococcaceae), Lactobacillales (eg, Enterococcaceae, Lactobacillaceae, Streptococcaceae) and Actinomycetales (eg, Actinomycetaceae, Micrococcaceae), the families Pasteurellaceae and Enterobacteriaceae and the genus Veillonella. Taxa decreased by PPIs include Bifidobacteriaceae, Ruminococcaceae, Lachnospiraceae and Mollicutes (findings in faecal samples based on 19 independent cohorts with 790 PPI users). CONCLUSION PPI use is associated with moderate alterations to upper and distal gut microbiota. The available data suggest that PPI-induced hypochlorhydria facilitates colonization of more distal parts of the digestive tract by upper gastrointestinal microbiota.
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Affiliation(s)
- Lukas Macke
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Christian Schulz
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Leandra Koletzko
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Peter Malfertheiner
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.,Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
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Lin L, Hou L, Deng Y, Zhao T, Wang B, Sun C. Acid suppression therapy and its association with spontaneous bacterial peritonitis incidence: A systemic review and meta-analysis. Hepatol Res 2020; 50:233-245. [PMID: 31667938 DOI: 10.1111/hepr.13447] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 10/02/2019] [Accepted: 10/04/2019] [Indexed: 12/16/2022]
Abstract
AIM It is well known that the use of proton pump inhibitor (PPI) is widespread in patients with liver cirrhosis. PPI counteracts H2 receptor inhibitor (H2 RA) with its strong acid suppression effect. However, there is always a concern that PPI use may increase spontaneous bacteria peritonitis (SBP) development in cirrhotic patients. We aimed to investigate the association between acid suppression therapy (i.e. PPI or H2 RA) and SBP through meta-analysis. METHODS We searched PubMed, Medline, Web of Science, Cochrane library, and Embase for relevant studies published up to April 2019. Pooled OR and 95% CI were calculated by a random-effects model. Funnel plots and Egger's tests were performed for the evaluation of publication bias. Non-parametric "trim-and-fill" tests were conducted for sensitivity analysis. RESULTS A total of 20 original articles including 9566 cirrhotic patients were analyzed. The overall meta-analysis highlighted that PPI use was associated with the risk of SBP (pooled OR 1.77, 95% CI 1.49-2.11). The conclusion was irrespective of study methods, whereas the result was inconsistent only in South America. However, the conclusion might not be stable enough and should be extrapolated with caution. Unlike PPI, we found H2 RA was not associated with SBP (pooled OR 1.06, 95% CI 0.75-1.48). CONCLUSIONS In conclusion, PPI use, but not H2 RA, will increase the incidence of SBP in cirrhotic patients. In addition, H2 RA might be beneficial for patients who require long-term acid suppression therapy.
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Affiliation(s)
- Lin Lin
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
| | - Lijun Hou
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
| | - You Deng
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Tianming Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
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Adverse outcomes of proton pump inhibitors in chronic liver disease: a systematic review and meta-analysis. Hepatol Int 2020; 14:385-398. [PMID: 31912308 DOI: 10.1007/s12072-019-10010-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 12/03/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIM Proton pump inhibitors (PPIs) are among the most commonly prescribed medications in the US, but their safety in cirrhosis has recently been questioned. We performed a meta-analysis of observational studies to evaluate the impact of PPIs on adverse clinical outcomes in the setting of chronic liver disease (CLD). METHODS We searched several databases from inception to 26 May 2019 to identify comparative studies evaluating the effect of PPIs in CLD. Outcomes of interest were the associations between PPIs use and the occurrence of hepatic encephalopathy, hepatocellular carcinoma, spontaneous bacterial peritonitis, bacterial infections, and mortality in CLD. We performed a meta-analysis in accordance to the PRISMA guidelines. RESULTS Of 14,662 papers evaluated, 47 studies with 169,806 participants were identified. Of these, 35 were cohort studies and 12 were case-control studies. The pooled odds ratio (OR) for hepatic encephalopathy in individuals with PPI users, compared with those without, was 2.31 (95% CI 1.63-3.28). The pooled OR for spontaneous bacterial peritonitis in individuals with PPI users was significantly higher compared with non-PPI users (OR = 1.72, 95% CI 1.42-2.09). Results were also consistent with a higher risk of the bacterial infections and mortality in PPI users compared with non-PPI users. For hepatocellular carcinoma, the final conclusion cannot be drawn because of the limited number of studies. CONCLUSIONS This study identifies a significant relationship between PPIs therapies and several specific adverse clinical outcomes in CLD. However, these results should be carefully considered given the potential selection bias and unmeasured confounding variables in observational studies, it may be reasonable to re-evaluate the need for PPIs in patients with CLD.
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Quigley EMM. The Microbiota-Gut-Liver Axis: Implications for the Pathophysiology of Liver Disease. LIVER IMMUNOLOGY 2020:125-137. [DOI: 10.1007/978-3-030-51709-0_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Chen D, Le TH, Shahidipour H, Read SA, Ahlenstiel G. The Role of Gut-Derived Microbial Antigens on Liver Fibrosis Initiation and Progression. Cells 2019; 8:E1324. [PMID: 31717860 PMCID: PMC6912265 DOI: 10.3390/cells8111324] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 10/22/2019] [Accepted: 10/23/2019] [Indexed: 12/12/2022] Open
Abstract
Intestinal dysbiosis has recently become known as an important driver of gastrointestinal and liver disease. It remains poorly understood, however, how gastrointestinal microbes bypass the intestinal mucosa and enter systemic circulation to enact an inflammatory immune response. In the context of chronic liver disease (CLD), insults that drive hepatic inflammation and fibrogenesis (alcohol, fat) can drastically increase intestinal permeability, hence flooding the liver with gut-derived microbiota. Consequently, this may result in exacerbated liver inflammation and fibrosis through activation of liver-resident Kupffer and stellate cells by bacterial, viral, and fungal antigens transported to the liver via the portal vein. This review summarizes the current understanding of microbial translocation in CLD, the cell-specific hepatic response to intestinal antigens, and how this drives the development and progression of hepatic inflammation and fibrosis. Further, we reviewed current and future therapies targeting intestinal permeability and the associated, potentially harmful anti-microbial immune response with respect to their potential in terms of limiting the development and progression of liver fibrosis and end-stage cirrhosis.
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Affiliation(s)
- Dishen Chen
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead 2145, NSW, Australia; (D.C.); (T.H.L.); (H.S.)
| | - Thanh H. Le
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead 2145, NSW, Australia; (D.C.); (T.H.L.); (H.S.)
- School of Medicine, Western Sydney University, Campbelltown 2560, NSW, Australia
| | - Haleh Shahidipour
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead 2145, NSW, Australia; (D.C.); (T.H.L.); (H.S.)
- Blacktown Medical School, Western Sydney University, Blacktown 2148, NSW, Australia
| | - Scott A. Read
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead 2145, NSW, Australia; (D.C.); (T.H.L.); (H.S.)
- Blacktown Medical School, Western Sydney University, Blacktown 2148, NSW, Australia
| | - Golo Ahlenstiel
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead 2145, NSW, Australia; (D.C.); (T.H.L.); (H.S.)
- Blacktown Medical School, Western Sydney University, Blacktown 2148, NSW, Australia
- Blacktown Hospital, Blacktown 2148, NSW, Australia
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