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Alenezy EK, Kandjani AE, Shaibani M, Trinchi A, Bhargava SK, Ippolito SJ, Sabri Y. Human breath analysis; Clinical application and measurement: An overview. Biosens Bioelectron 2025; 278:117094. [PMID: 40037038 DOI: 10.1016/j.bios.2024.117094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 12/05/2024] [Accepted: 12/21/2024] [Indexed: 03/06/2025]
Abstract
Human breath has been recognized as a complex yet predictive mixture of volatile organic compounds (VOCs) and inorganic gas species that can be utilized to non-invasively diagnose common diseases. Current laboratory techniques such as gas chromatography/mass spectrometry (GC/MS) and high-performance liquid chromatography (HPLC), are capable of VOC detection down to ppm concentrations. However, these methods are expensive, non-portable, require pre-processing of the exhaled VOCs, and expert operators, making them unsuitable for wide-spread use. Portable gas sensors have various advantages over other methods used in gas analysis, including ease of transportation, reduced treatment costs, fast results, and improved patient experience. Recent advancements in gas sensing technologies have enabled such devices to be used to diagnose, predict, and monitor a wide range of diseases and conditions, however, many challenges need still need to be addressed (i.e., sensitivity and selectivity) before they can be employed for such applications. Although nanotechnology has greatly improved the performance of gas sensor materials and their capacity to detect VOCs in human breath, issues around repeatability and accuracy remain, as well as adequateness due to the close proximity of the human body and the sensor device. This review focuses on how recent advancements in nanotechnology and solid-state materials have enabled VOC gas sensors to evolve into miniaturized, sensitive and selective devices for monitoring human breath in clinical applications. An introduction to the key aspects of breath analysis, including sources of VOCs in human breath and their role in disease diagnosis, is discussed. Furthermore, the current limitations and future prospects of such gas sensors for breath monitoring applications are also discussed in detail.
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Affiliation(s)
- Ebtsam K Alenezy
- Department of chemistry, College of Science, Jouf University, Sakaka, Aljouf, 72341, Saudi Arabia.
| | - Ahmad E Kandjani
- Commonwealth Scientific and Industrial Research Organisation (CSIRO), Manufacturing Research Unit, Clayton, VIC, 3168, Australia.
| | - Mahdokht Shaibani
- School of Engineering, RMIT University, Melbourne, Victoria, 3001, Australia.
| | - Adrian Trinchi
- Commonwealth Scientific and Industrial Research Organisation (CSIRO), Manufacturing Research Unit, Clayton, VIC, 3168, Australia.
| | - Suresh K Bhargava
- Centre for Advanced Materials and Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO Box 2476, Melbourne, Victoria, 3001, Australia.
| | - Samuel J Ippolito
- Centre for Advanced Materials and Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO Box 2476, Melbourne, Victoria, 3001, Australia; School of Engineering, RMIT University, Melbourne, Victoria, 3001, Australia.
| | - Ylias Sabri
- Centre for Advanced Materials and Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO Box 2476, Melbourne, Victoria, 3001, Australia; School of Engineering, RMIT University, Melbourne, Victoria, 3001, Australia.
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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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3
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Shah A, Spannenburg L, Thite P, Morrison M, Fairlie T, Koloski N, Kashyap PC, Pimentel M, Rezaie A, Gores GJ, Jones MP, Holtmann G. Small intestinal bacterial overgrowth in chronic liver disease: an updated systematic review and meta-analysis of case-control studies. EClinicalMedicine 2025; 80:103024. [PMID: 39844931 PMCID: PMC11751576 DOI: 10.1016/j.eclinm.2024.103024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 12/05/2024] [Accepted: 12/12/2024] [Indexed: 01/24/2025] Open
Abstract
Background Small Intestinal Bacterial Overgrowth (SIBO) has been implicated in the pathophysiology of chronic liver disease (CLD). We conducted a systematic review and meta-analysis to assess and compare the prevalence of SIBO among CLD patients (with and without with complications of end stage liver disease) and healthy controls. Methods Electronic databases were searched from inception up to July-2024 for case-control studies reporting SIBO in CLD. Prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) of SIBO in patients with CLD and controls were calculated utilizing a random-effects model. The protocol was prospectively registered with PROSPERO (CRD42022379578). Findings The final dataset included 34 case-control studies with 2130 CLD patients and 1222 controls. Overall, the odds for SIBO prevalence in CLD patients compared to controls was 6.7 (95% CI 4.6-9.7, p < 0.001). Although the prevalence of SIBO among patients with CLD with cirrhosis was higher at 42.9% (95% CI: 35.9-50.2) compared to 36.9% (95% CI: 27.4-47.6) in those without cirrhosis, this difference failed statistical significance. However, CLD patients with decompensated cirrhosis had a significantly higher prevalence of SIBO compared to those with compensated cirrhosis, with an OR of 2.6 (95% CI: 1.5-4.5, p < 0.001). Additionally, the prevalence of SIBO was significantly higher in CLD patients with portal hypertension (PHT) than in those without PHT, with an OR of 2.1 (95% CI: 1.4-3.1, p < 0.001). The highest prevalence of SIBO was observed in patients with spontaneous bacterial peritonitis (SBP) (57.7%, 95% CI 38.8-74.5), followed by patients with hepatic encephalopathy (41.0%, 95% CI 16.0-72.3) and patients with variceal bleed (39.5%, 95% CI 12.1-75.6). Interpretation Overall, there is a significantly increased prevalence of SIBO in CLD patients compared to controls. The prevalence is even higher in CLD patients with PHT, especially those with SBP. This meta-analysis suggests that SIBO is associated with complications of CLD and potentially linked to the progression of CLD. Funding National Health and Medical Research Council, Centre for Research Excellence (APP170993).
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Affiliation(s)
- Ayesha Shah
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
- Translational Research Institute, QLD, Australia
| | - Liam Spannenburg
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
| | - Parag Thite
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
| | - Mark Morrison
- Faculty of Medicine, University of Queensland Frazer Institute, Woolloongabba, QLD, Australia
| | - Thomas Fairlie
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
- Translational Research Institute, QLD, Australia
| | - Natasha Koloski
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
- Translational Research Institute, QLD, Australia
| | - Purna C. Kashyap
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Mark Pimentel
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Ali Rezaie
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Gregory J. Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Michael P. Jones
- Macquarie University, Department of Psychology, Sydney, NSW, Australia
| | - Gerald Holtmann
- Faculty of Medicine, University of Queensland, Australia
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Australia
- Translational Research Institute, QLD, Australia
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Incicco S, Angeli P, Piano S. Infectious Complications of Portal Hypertension. Clin Liver Dis 2024; 28:525-539. [PMID: 38945641 DOI: 10.1016/j.cld.2024.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Patients with cirrhosis and clinically significant portal hypertension are at high risk of developing bacterial infections (BIs) that are the most common trigger of acute decompensation and acute-on-chronic liver failure. Furthermore, after decompensation, the risk of developing BIs further increases in an ominous vicious circle. BIs may be subtle, and they should be ruled out in all patients at admission and in case of deterioration. Timely administration of adequate empirical antibiotics is the cornerstone of treatment. Herein, we reviewed current evidences about pathogenesis, clinical implications and management of BIs in patients with cirrhosis and portal hypertension.
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Affiliation(s)
- Simone Incicco
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy.
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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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Lombardi M, Troisi J, Motta BM, Torre P, Masarone M, Persico M. Gut-Liver Axis Dysregulation in Portal Hypertension: Emerging Frontiers. Nutrients 2024; 16:1025. [PMID: 38613058 PMCID: PMC11013091 DOI: 10.3390/nu16071025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/27/2024] [Accepted: 03/30/2024] [Indexed: 04/14/2024] Open
Abstract
Portal hypertension (PH) is a complex clinical challenge with severe complications, including variceal bleeding, ascites, hepatic encephalopathy, and hepatorenal syndrome. The gut microbiota (GM) and its interconnectedness with human health have emerged as a captivating field of research. This review explores the intricate connections between the gut and the liver, aiming to elucidate how alterations in GM, intestinal barrier function, and gut-derived molecules impact the development and progression of PH. A systematic literature search, following PRISMA guidelines, identified 12 original articles that suggest a relationship between GM, the gut-liver axis, and PH. Mechanisms such as dysbiosis, bacterial translocation, altered microbial structure, and inflammation appear to orchestrate this relationship. One notable study highlights the pivotal role of the farnesoid X receptor axis in regulating the interplay between the gut and liver and proposes it as a promising therapeutic target. Fecal transplantation experiments further emphasize the pathogenic significance of the GM in modulating liver maladies, including PH. Recent advancements in metagenomics and metabolomics have expanded our understanding of the GM's role in human ailments. The review suggests that addressing the unmet need of identifying gut-liver axis-related metabolic and molecular pathways holds potential for elucidating pathogenesis and directing novel therapeutic interventions.
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Affiliation(s)
- Martina Lombardi
- Department of Chemistry and Biology “A. Zambelli”, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy;
- European Institute of Metabolomics (EIM) Foundation, Via G. Puccini, 3, 84081 Baronissi, SA, Italy
| | - Jacopo Troisi
- Department of Chemistry and Biology “A. Zambelli”, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy;
- European Institute of Metabolomics (EIM) Foundation, Via G. Puccini, 3, 84081 Baronissi, SA, Italy
- Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, SA, Italy; (B.M.M.); (P.T.); (M.M.)
| | - Benedetta Maria Motta
- Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, SA, Italy; (B.M.M.); (P.T.); (M.M.)
| | - Pietro Torre
- Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, SA, Italy; (B.M.M.); (P.T.); (M.M.)
| | - Mario Masarone
- Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, SA, Italy; (B.M.M.); (P.T.); (M.M.)
| | - Marcello Persico
- Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, SA, Italy; (B.M.M.); (P.T.); (M.M.)
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Terbah R, Testro A, Gow P, Majumdar A, Sinclair M. Portal Hypertension in Malnutrition and Sarcopenia in Decompensated Cirrhosis-Pathogenesis, Implications and Therapeutic Opportunities. Nutrients 2023; 16:35. [PMID: 38201864 PMCID: PMC10780673 DOI: 10.3390/nu16010035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 12/18/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024] Open
Abstract
Malnutrition and sarcopenia are highly prevalent in patients with decompensated cirrhosis and are associated with poorer clinical outcomes. Their pathophysiology is complex and multifactorial, with protein-calorie malnutrition, systemic inflammation, reduced glycogen stores and hormonal imbalances all well reported. The direct contribution of portal hypertension to these driving factors is however not widely documented in the literature. This review details the specific mechanisms by which portal hypertension directly contributes to the development of malnutrition and sarcopenia in cirrhosis. We summarise the existing literature describing treatment strategies that specifically aim to reduce portal pressures and their impact on nutritional and muscle outcomes, which is particularly relevant to those with end-stage disease awaiting liver transplantation.
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Affiliation(s)
- Ryma Terbah
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Adam Testro
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Paul Gow
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Avik Majumdar
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Marie Sinclair
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
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8
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Torre A, Cisneros-Garza LE, Castillo-Barradas M, Navarro-Alvarez N, Sandoval-Salas R, González-Huezo MS, Pérez-Hernández JL, Méndez-Guerrero O, Ruiz-Manríquez JA, Trejo-Estrada R, Chavez-Tapia NC, Solís-Gasca LC, Moctezuma-Velázquez C, Aguirre-Valádez J, Flores-Calderón J, Higuera-de-la-Tijera F, García-Juárez I, Canedo-Castillo NA, Malé-Velázquez R, Montalvo-Gordon I, Vilatobá M, Márquez-Guillén E, Córdova-Gallardo J, Flores-García NC, Miranda-Zazueta G, Martínez-Saldívar BI, Páez-Zayas VM, Muñoz-Espinosa LE, Solís-Galindo FA. Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology. Ann Hepatol 2023; 28:101140. [PMID: 37482299 DOI: 10.1016/j.aohep.2023.101140] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/26/2023] [Accepted: 05/31/2023] [Indexed: 07/25/2023]
Abstract
Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.
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Affiliation(s)
- Aldo Torre
- Metabolic Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
| | - Laura Esthela Cisneros-Garza
- Gastroenterology and Hepatology Department, Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico
| | | | - Nalu Navarro-Alvarez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Osvely Méndez-Guerrero
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Luis Carlos Solís-Gasca
- Gastroenterology Department, Hospital General de Zona #12 Benito Juárez del Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico
| | - Carlos Moctezuma-Velázquez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Medicine - Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | | | - Judith Flores-Calderón
- Pediatrics Department, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | | | - Ignacio García-Juárez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Iaarah Montalvo-Gordon
- Clinic of Gastrointestinal and Hepatic Specialties, Hospital Faro del Mayab, Mérida, Yucatán, Mexico
| | - Mario Vilatobá
- Transplant Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Ernesto Márquez-Guillén
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Hospital Ángeles del Pedregal, Mexico City, Mexico
| | - Jacqueline Córdova-Gallardo
- Hepatology Department - General Surgery Service, Hospital General Dr. Manuel Gea González, Mexico City, Mexico
| | - Nayeli Cointa Flores-García
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Godolfino Miranda-Zazueta
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Linda Elsa Muñoz-Espinosa
- Universidad Autónoma de Nuevo León. Liver Unit, Department of Internal Medicine, University Hospital 'Dr. José E. González', Monterrey, Nuevo León, Mexico
| | - Francisco Alfonso Solís-Galindo
- Gastroenterology Department, Unidad Médica de Alta Especialidad # 71 Instituto Mexicano del Seguro Social, Torreón, Coahuila, Mexico
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9
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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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10
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Liu Y, Li Y, Xie J. Traditional Chinese Medicine Strategy for Treating Major Depressive Disorder Based on a Famous Formulation-Baweixiaoyaosan. AN ACAD BRAS CIENC 2023; 95:e20220676. [PMID: 37255171 DOI: 10.1590/0001-3765202320220676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Accepted: 12/13/2022] [Indexed: 06/01/2023] Open
Abstract
In this study, systematic pharmacological methods were used to reveal the potential pharmacological targets of baweixiaoyaosan in the treatment of major depressive disorder (MDD). We identified 133 potential active compounds through data mining and absorption, distribution, metabolism, and excretion evaluation systems. Then, the target of potential active compounds is predicted by a system model based on random forest and support vector machine methods. Next, construct herbal ingredient-target networks and target-disease networks for further analysis of multi-directional treatment methods. At the same time, we also performed gene ontology enrichment analysis, tissue location analysis, and pathway analysis on 76 potential targets. Finally, we conducted the Jun-Chen-Zuo-Shi compatibility analysis of the formula and scientifically explained the different functions of different herbs in the formula. In short, we found that the formula mainly exerts the effect of treating MDD through the four functional modules of inflammation inhibition, neuroprotection, monoamine neurotransmitter and liver. This research not only explores the mechanism of Traditional Chinese Medicine treatment of MDD from a multi-scale perspective, but also provides a reference for future research on BWXYS. It plays a role in promoting the widespread use of BWXYS.
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Affiliation(s)
- Yongwei Liu
- Dalian University of Technology, Chemical Engineering Institute, Linggong Road, 2, 116023 Dalian, Liaoning, China
| | - Yan Li
- Dalian University of Technology, Chemical Engineering Institute, Linggong Road, 2, 116023 Dalian, Liaoning, China
| | - Jing Xie
- Dalian University of Technology, Chemical Engineering Institute, Linggong Road, 2, 116023 Dalian, Liaoning, China
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11
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Qin T, Chen X, Meng J, Guo Q, Xu S, Hou S, Yuan Z, Zhang W. The role of curcumin in the liver-gut system diseases: from mechanisms to clinical therapeutic perspective. Crit Rev Food Sci Nutr 2023; 64:8822-8851. [PMID: 37096460 DOI: 10.1080/10408398.2023.2204349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
Abstract
Natural products have provided abundant sources of lead compounds for new drug discovery and development over the past centuries. Curcumin is a lipophilic polyphenol isolated from turmeric, a plant used in traditional Asian medicine for centuries. Despite the low oral bioavailability, curcumin exhibits profound medicinal value in various diseases, especially liver and gut diseases, bringing an interest in the paradox of its low bioavailability but high bioactivity. Several latest studies suggest that curcumin's health benefits may rely on its positive gastrointestinal effects rather than its poor bioavailability solely. Microbial antigens, metabolites, and bile acids regulate metabolism and immune responses in the intestine and liver, suggesting the possibility that the liver-gut axis bidirectional crosstalk controls gastrointestinal health and diseases. Accordingly, these pieces of evidence have evoked great interest in the curcumin-mediated crosstalk among liver-gut system diseases. The present study discussed the beneficial effects of curcumin against common liver and gut diseases and explored the underlying molecular targets, as well as collected evidence from human clinical studies. Moreover, this study summarized the roles of curcumin in complex metabolic interactions in liver and intestine diseases supporting the application of curcumin in the liver-gut system as a potential therapeutic option, which opens an avenue for clinical use in the future.
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Affiliation(s)
- Tingting Qin
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Xiuying Chen
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Jiahui Meng
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Qianqian Guo
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Shan Xu
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Shanshan Hou
- Department of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, China
| | - Ziqiao Yuan
- Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Wenzhou Zhang
- Department of Pharmacy, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
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12
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Plauzolles A, Uras S, Pénaranda G, Bonnet M, Dukan P, Retornaz F, Halfon P. Small Intestinal Bacterial Overgrowths and Intestinal Methanogen Overgrowths Breath Testing in a Real-Life French Cohort. Clin Transl Gastroenterol 2023; 14:e00556. [PMID: 36515897 PMCID: PMC10132713 DOI: 10.14309/ctg.0000000000000556] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 12/02/2022] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Breath testing has become a widely used tool to diagnose small intestinal bacterial overgrowths (SIBOs) and intestinal methanogen overgrowths (IMOs) in clinical settings. Owing to the heterogeneity in clinical manifestations and lack of standardization among centers performing breath testing, SIBO and IMO can be easily overlooked by the clinician. We studied the prevalence and symptoms of SIBO/IMO in French patients referred for breath testing after seeking medical advice. METHODS Breath test data and symptoms of 331 patients were assessed for SIBO/IMO using the H 2 /CH 4 lactulose breath test (LBT). Wilcoxon test or χ 2 test were used to compare patients with SIBO/IMO with patients without SIBO/IMO. LBT positive patients (H 2 +, CH 4 +, and CH 4 +/H 2 +) were compared using Kruskal-Wallis test for continuous data or χ 2 test for categorical data. RESULTS Among the 186 (68.1%) patients tested positive for an overgrowth with 40.3%, 47.3%, and 12.4% for H 2 +, CH 4 + and CH 4 +/H 2 +, respectively, the presence of diarrhea was significantly increased in hydrogen type overgrowths ( P < 0.001). No significant difference according to age, gender, and symptoms was associated with a positive test except for joint pain that was less prevalent among LBT positive patients ( P = 0.038). In 86.5% of IMOs, positivity with CH 4 values ≥10 ppm could be identified at baseline. DISCUSSION There are little discriminating symptoms that can help the clinician to identify patients likely to have a SIBO/IMO. However, SIBO/IMOs remain a common disorder widely underdiagnosed that need further studies to better apprehend functional bowel disorders.
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Affiliation(s)
- Anne Plauzolles
- Clinical Research and R&D Department, Laboratoire Européen Alphabio Biogroup, Marseille, France
| | - Stella Uras
- Clinical Research and R&D Department, Laboratoire Européen Alphabio Biogroup, Marseille, France
- Faculty of Sciences, Aix-Marseille University, Marseille, France
| | - Guillaume Pénaranda
- Clinical Research and R&D Department, Laboratoire Européen Alphabio Biogroup, Marseille, France
| | - Marion Bonnet
- Clinical Research and R&D Department, Laboratoire Européen Alphabio Biogroup, Marseille, France
| | - Patrick Dukan
- Infectious and Internal Medicine Department, Hôpital Européen Marseille, Marseille, France
| | - Frédérique Retornaz
- Infectious and Internal Medicine Department, Hôpital Européen Marseille, Marseille, France
| | - Philippe Halfon
- Clinical Research and R&D Department, Laboratoire Européen Alphabio Biogroup, Marseille, France
- Infectious and Internal Medicine Department, Hôpital Européen Marseille, Marseille, France
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Muñoz L, Caparrós E, Albillos A, Francés R. The shaping of gut immunity in cirrhosis. Front Immunol 2023; 14:1139554. [PMID: 37122743 PMCID: PMC10141304 DOI: 10.3389/fimmu.2023.1139554] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 03/27/2023] [Indexed: 05/02/2023] Open
Abstract
Cirrhosis is the common end-stage of chronic liver diseases of different etiology. The altered bile acids metabolism in the cirrhotic liver and the increase in the blood-brain barrier permeability, along with the progressive dysbiosis of intestinal microbiota, contribute to gut immunity changes, from compromised antimicrobial host defense to pro-inflammatory adaptive responses. In turn, these changes elicit a disruption in the epithelial and gut vascular barriers, promoting the increased access of potential pathogenic microbial antigens to portal circulation, further aggravating liver disease. After summarizing the key aspects of gut immunity during homeostasis, this review is intended to update the contribution of liver and brain metabolites in shaping the intestinal immune status and, in turn, to understand how the loss of homeostasis in the gut-associated lymphoid tissue, as present in cirrhosis, cooperates in the advanced chronic liver disease progression. Finally, several therapeutic approaches targeting the intestinal homeostasis in cirrhosis are discussed.
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Affiliation(s)
- Leticia Muñoz
- Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Esther Caparrós
- Grupo de Inmunobiología Hepática e Intestinal, Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain
- Instituto de Investigación Sanitaria ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain
| | - Agustín Albillos
- Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Departamento de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
- *Correspondence: Agustín Albillos, ; Rubén Frances,
| | - Rubén Francés
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Grupo de Inmunobiología Hepática e Intestinal, Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain
- Instituto de Investigación Sanitaria ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain
- Instituto de Investigación, Desarrollo e Innovación en Biotecnologiía Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Elche, Spain
- *Correspondence: Agustín Albillos, ; Rubén Frances,
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Sroka N, Rydzewska-Rosołowska A, Kakareko K, Rosołowski M, Głowińska I, Hryszko T. Show Me What You Have Inside-The Complex Interplay between SIBO and Multiple Medical Conditions-A Systematic Review. Nutrients 2022; 15:nu15010090. [PMID: 36615748 PMCID: PMC9824151 DOI: 10.3390/nu15010090] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/18/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open
Abstract
The microbiota, as a complex of microorganisms in a particular ecosystem, is part of the wider term-microbiome, which is defined as the set of all genetic content in the microbial community. Imbalanced gut microbiota has a great impact on the homeostasis of the organism. Dysbiosis, as a disturbance in bacterial balance, might trigger or exacerbate the course of different pathologies. Small intestinal bacterial overgrowth (SIBO) is a disorder characterized by differences in quantity, quality, and location of the small intestine microbiota. SIBO underlies symptoms associated with functional gastrointestinal disorders (FGD) as well as may alter the presentation of chronic diseases such as heart failure, diabetes, etc. In recent years there has been growing interest in the influence of SIBO and its impact on the whole human body as well as individual systems. Therefore, we aimed to investigate the co-existence of SIBO with different medical conditions. The PubMed database was searched up to July 2022 and we found 580 original studies; inclusion and exclusion criteria let us identify 112 eligible articles, which are quoted in this paper. The present SIBO diagnostic methods could be divided into two groups-invasive, the gold standard-small intestine aspirate culture, and non-invasive, breath tests (BT). Over the years scientists have explored SIBO and its associations with other diseases. Its role has been confirmed not only in gastroenterology but also in cardiology, endocrinology, neurology, rheumatology, and nephrology. Antibiotic therapy could reduce SIBO occurrence resulting not only in the relief of FGD symptoms but also manifestations of comorbid diseases. Although more research is needed, the link between SIBO and other diseases is an important pathway for scientists to follow.
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Affiliation(s)
- Natalia Sroka
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
- Correspondence:
| | - Alicja Rydzewska-Rosołowska
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| | - Katarzyna Kakareko
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| | - Mariusz Rosołowski
- Department of Internal Medicine and Hypertension, Medical University of Białystok, 15-540 Białystok, Poland
| | - Irena Głowińska
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
| | - Tomasz Hryszko
- 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland
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15
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Haj Ali S, Abu Sneineh A, Hasweh R. Nutritional assessment in patients with liver cirrhosis. World J Hepatol 2022; 14:1694-1703. [PMID: 36185724 PMCID: PMC9521456 DOI: 10.4254/wjh.v14.i9.1694] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/09/2022] [Accepted: 09/09/2022] [Indexed: 02/06/2023] Open
Abstract
Malnutrition is a liver cirrhosis complication affecting more than 20%-50% of patients. Although the term can refer to either nutrient deficiency or excess, it usually relates to undernutrition in cirrhosis settings. Frailty is defined as limited physical function due to muscle weakness, whereas sarcopenia is defined as muscle mass loss and an advanced malnutrition stage. The pathogenesis of malnutrition in liver cirrhosis is multifactorial, including decreased oral intake, maldigestion/malabsorption, physical inactivity, hyperammonemia, hypermetabolism, altered macronutrient metabolism and gut microbiome dysbiosis. Patients with chronic liver disease with a Body Mass Index of < 18.5 kg/m2 and/or decompensated cirrhosis or Child-Pugh class C are at the highest risk of malnutrition. For patients at risk of malnutrition, a detailed nutritional assessment is required, typically including a history and physical examination, laboratory testing, global assessment tools and body composition testing. The latter can be done using anthropometry, cross-sectional imaging including computed tomography or magnetic resonance, bioelectrical impedance analysis and dual-energy X-ray absorptiometry. A multidisciplinary team should screen for and treat malnutrition in patients with cirrhosis. Malnutrition and sarcopenia are associated with an increased risk of complications and a poor prognosis in patients with liver cirrhosis; thus, it is critical to diagnose these conditions early and initiate the appropriate nutritional therapy. In this review, we describe the prevalence and pathogenesis of malnutrition in liver cirrhosis patients and discuss the best diagnostic approach to nutritional assessment for them.
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Affiliation(s)
- Sara Haj Ali
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Salt 19117, Jordan
| | - Awni Abu Sneineh
- Department of Gastroenterology and Hepatology, University of Jordan, Faculty of Medicine, Amman 11942, Jordan
| | - Reem Hasweh
- Department of Internal Medicine, Faculty of Medicine, Al-Balqa Applied University, Salt 19117, Jordan
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Geng W, Zhang Y, Yang J, Zhang J, Zhao J, Wang J, Jia L, Wang Y. Identification of a novel probiotic and its protective effects on NAFLD via modulating gut microbial community. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2022; 102:4620-4628. [PMID: 35174500 DOI: 10.1002/jsfa.11820] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 01/12/2022] [Accepted: 02/17/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is becoming the most common progressive liver diseases. Therapeutic strategy based on gut-liver axis and probiotics is a promising approach for the treatment of NAFLD. However, rare probiotics have been applied in NAFLD treatment, and the involved molecular mechanism is not entirely clear. RESULTS We initially identified a novel functional probiotic, Lactobacillus kefiranofaciens ZW3, on the lipid deposition by a simple and rapid zebrafish model. Supplementation with ZW3 to the methionine and choline deficient (MCD) diet induced NAFLD rats could improve the liver impairments and reduce inflammation through TLR4-MyD88 and JNK signaling pathways. Moreover, ZW3 modulated gut microbiota by promoting relative abundance of Firmicutes and Lactobacillus, decreasing the abundance of Escherichia-Shigella and Bacteroides. Functional prediction of microbiome showed ZW3 presented potential enhancement on carbohydrate and lipid metabolism, cell process control and signal transduction processes, and reduced several human diseases. CONCLUSION This present study identified a novel probiotic and its protective effects on NAFLD, and interpreted the interactions of ZW3 with the immune system and gut microbiota involved in gut-liver axis. © 2022 Society of Chemical Industry.
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Affiliation(s)
- Weitao Geng
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Yang Zhang
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Jingnan Yang
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Jing Zhang
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Jingqi Zhao
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Jinju Wang
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Longgang Jia
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
| | - Yanping Wang
- College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin, China
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Upper Gastrointestinal Cancer and Liver Cirrhosis. Cancers (Basel) 2022; 14:cancers14092269. [PMID: 35565397 PMCID: PMC9105927 DOI: 10.3390/cancers14092269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/26/2022] [Accepted: 04/29/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary There is a higher incidence rate of upper gastrointestinal cancer in those with liver cirrhosis. The contributing factors include gastric ulcers, congestive gastropathy, zinc deficiency, alcohol drinking, tobacco use and gut microbiota. Most of the de novo malignancies that develop after liver transplantation for cirrhotic patients are upper gastrointestinal cancers. The surgical risk of upper gastrointestinal cancers in cirrhotic patients with advanced liver cirrhosis is higher. Abstract The extended scope of upper gastrointestinal cancer can include esophageal cancer, gastric cancer and pancreatic cancer. A higher incidence rate of gastric cancer and esophageal cancer in patients with liver cirrhosis has been reported. It is attributable to four possible causes which exist in cirrhotic patients, including a higher prevalence of gastric ulcers and congestive gastropathy, zinc deficiency, alcohol drinking and tobacco use and coexisting gut microbiota. Helicobacter pylori infection enhances the development of gastric cancer. In addition, Helicobacter pylori, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans also contribute to the development of pancreatic cancer in cirrhotic patients. Cirrhotic patients (especially those with alcoholic liver cirrhosis) who undergo liver transplantation have a higher overall risk of developing de novo malignancies. Most de novo malignancies are upper gastrointestinal malignancies. The prognosis is usually poor. Considering the surgical risk of upper gastrointestinal cancer among those with liver cirrhosis, a radical gastrectomy with D1 or D2 lymph node dissection can be undertaken in Child class A patients. D1 lymph node dissection can be performed in Child class B patients. Endoscopic submucosal dissection for gastric cancer or esophageal cancer can be undertaken safely in selected cirrhotic patients. In Child class C patients, a radical gastrectomy is potentially fatal. Pancreatic radical surgery should be avoided in those with liver cirrhosis with Child class B or a MELD score over 15. The current review focuses on the recent reports on some factors in liver cirrhosis that contribute to the development of upper gastrointestinal cancer. Quitting alcohol drinking and tobacco use is important. How to decrease the risk of the development of gastrointestinal cancer in those with liver cirrhosis remains a challenging problem.
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Preventing Bacterial Translocation in Patients with Leaky Gut Syndrome: Nutrition and Pharmacological Treatment Options. Int J Mol Sci 2022; 23:ijms23063204. [PMID: 35328624 PMCID: PMC8949204 DOI: 10.3390/ijms23063204] [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] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/14/2022] [Accepted: 03/14/2022] [Indexed: 12/11/2022] Open
Abstract
Leaky gut syndrome is a medical condition characterized by intestinal hyperpermeability. Since the intestinal barrier is one of the essential components maintaining homeostasis along the gastrointestinal tract, loss of its integrity due to changes in bacterial composition, decreased expression levels of tight junction proteins, and increased concentration of pro-inflammatory cytokines may lead to intestinal hyperpermeability followed by the development of gastrointestinal and non-gastrointestinal diseases. Translocation of microorganisms and their toxic metabolites beyond the gastrointestinal tract is one of the fallouts of the leaky gut syndrome. The presence of intestinal bacteria in sterile tissues and distant organs may cause damage due to chronic inflammation and progression of disorders, including inflammatory bowel diseases, liver cirrhosis, and acute pancreatitis. Currently, there are no medical guidelines for the treatment or prevention of bacterial translocation in patients with the leaky gut syndrome; however, several studies suggest that dietary intervention can improve barrier function and restrict bacteria invasion. This review contains current literature data concerning the influence of diet, dietary supplements, probiotics, and drugs on intestinal permeability and bacterial translocation.
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Nutritional therapy to cirrhotic patients on transplantation waiting lists. JOURNAL OF LIVER TRANSPLANTATION 2022. [DOI: 10.1016/j.liver.2021.100060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Amedei A, Gitto S, Campani C, Marra F. Probiotics and the gut-liver axis. PROBIOTICS 2022:467-481. [DOI: 10.1016/b978-0-323-85170-1.00003-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Park JW, Kim SE, Lee NY, Kim JH, Jung JH, Jang MK, Park SH, Lee MS, Kim DJ, Kim HS, Suk KT. Role of Microbiota-Derived Metabolites in Alcoholic and Non-Alcoholic Fatty Liver Diseases. Int J Mol Sci 2021; 23:426. [PMID: 35008852 PMCID: PMC8745242 DOI: 10.3390/ijms23010426] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/28/2021] [Accepted: 12/28/2021] [Indexed: 12/12/2022] Open
Abstract
Chronic liver disease encompasses diseases that have various causes, such as alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Gut microbiota dysregulation plays a key role in the pathogenesis of ALD and NAFLD through the gut-liver axis. The gut microbiota consists of various microorganisms that play a role in maintaining the homeostasis of the host and release a wide number of metabolites, including short-chain fatty acids (SCFAs), peptides, and hormones, continually shaping the host's immunity and metabolism. The integrity of the intestinal mucosal and vascular barriers is crucial to protect liver cells from exposure to harmful metabolites and pathogen-associated molecular pattern molecules. Dysbiosis and increased intestinal permeability may allow the liver to be exposed to abundant harmful metabolites that promote liver inflammation and fibrosis. In this review, we introduce the metabolites and components derived from the gut microbiota and discuss their pathologic effect in the liver alongside recent advances in molecular-based therapeutics and novel mechanistic findings associated with the gut-liver axis in ALD and NAFLD.
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Affiliation(s)
- Ji-Won Park
- Department of Internal Medicine, Hallym University Sacred Heart Hospital of Hallym University Medical Center, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si 14068, Korea; (J.-W.P.); (S.-E.K.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
| | - Sung-Eun Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital of Hallym University Medical Center, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si 14068, Korea; (J.-W.P.); (S.-E.K.)
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
| | - Na Young Lee
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
- Department of Internal Medicine, Chuncheon Sacred Heart Hospital of Hallym University Medical Center, 77, Sakju-ro, Chuncheon-si 24253, Korea
| | - Jung-Hee Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
- Department of Internal Medicine, Dongtan Sacred Heart Hospital of Hallym University Medical Center, 7, Keunjaebong-gil, Hwaseong-si 445-907, Korea
| | - Jang-Han Jung
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
- Department of Internal Medicine, Dongtan Sacred Heart Hospital of Hallym University Medical Center, 7, Keunjaebong-gil, Hwaseong-si 445-907, Korea
| | - Myoung-Kuk Jang
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
- Department of Internal Medicine, Kangdong Sacred Heart Hospital of Hallym University Medical Center, 18, Cheonho-daero 173-gil, Gangdong-gu, Seoul 05355, Korea
| | - Sang-Hoon Park
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
- Department of Internal Medicine, Kangnam Sacred Heart Hospital of Hallym University Medical Center, 1, Singil-ro, Yeongdeungpo-gu, Seoul 07441, Korea
| | - Myung-Seok Lee
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
- Department of Internal Medicine, Kangnam Sacred Heart Hospital of Hallym University Medical Center, 1, Singil-ro, Yeongdeungpo-gu, Seoul 07441, Korea
| | - Dong-Joon Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
- Department of Internal Medicine, Chuncheon Sacred Heart Hospital of Hallym University Medical Center, 77, Sakju-ro, Chuncheon-si 24253, Korea
| | - Hyoung-Su Kim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
- Department of Internal Medicine, Kangdong Sacred Heart Hospital of Hallym University Medical Center, 18, Cheonho-daero 173-gil, Gangdong-gu, Seoul 05355, Korea
| | - Ki Tae Suk
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon-si 24252, Korea; (N.Y.L.); (J.-H.K.); (J.-H.J.); (M.-K.J.); (S.-H.P.); (M.-S.L.); (D.-J.K.)
- Department of Internal Medicine, Chuncheon Sacred Heart Hospital of Hallym University Medical Center, 77, Sakju-ro, Chuncheon-si 24253, Korea
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Bi C, Xiao G, Liu C, Yan J, Chen J, Si W, Zhang J, Liu Z. Molecular Immune Mechanism of Intestinal Microbiota and Their Metabolites in the Occurrence and Development of Liver Cancer. Front Cell Dev Biol 2021; 9:702414. [PMID: 34957088 PMCID: PMC8693382 DOI: 10.3389/fcell.2021.702414] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 11/11/2021] [Indexed: 12/12/2022] Open
Abstract
Intestinal microorganisms are closely associated with immunity, metabolism, and inflammation, and play an important role in health and diseases such as inflammatory bowel disease, diabetes, cardiovascular disease, Parkinson’s disease, and cancer. Liver cancer is one of the most fatal cancers in humans. Most of liver cancers are slowly transformed from viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease. However, the relationship between intestinal microbiota and their metabolites, including short-chain fatty acids, bile acids, indoles, and ethanol, and liver cancer remains unclear. Here, we summarize the molecular immune mechanism of intestinal microbiota and their metabolites in the occurrence and development of liver cancer and reveal the important role of the microbiota-gut-liver axis in liver cancer. In addition, we describe how the intestinal flora can be balanced by antibiotics, probiotics, postbiotics, and fecal bacteria transplantation to improve the treatment of liver cancer. This review describes the immunomolecular mechanism of intestinal microbiota and their metabolites in the occurrence and development of hepatic cancer and provides theoretical evidence support for future clinical practice.
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Affiliation(s)
- Chenchen Bi
- Department of Pharmacology, Medical College of Shaoxing University, Shaoxing, China
| | - Geqiong Xiao
- Department of Oncology, Affiliated Hospital of Shaoxing University, Shaoxing, China
| | - Chunyan Liu
- Department of Clinical Medicine, Shaoxing People's Hospital, Shaoxing, China
| | - Junwei Yan
- Department of Pharmacology, Medical College of Shaoxing University, Shaoxing, China
| | - Jiaqi Chen
- Department of Pharmacology, Medical College of Shaoxing University, Shaoxing, China
| | - Wenzhang Si
- Department of General Surgery, Affiliated Hospital of Shaoxing University, Shaoxing, China
| | - Jian Zhang
- Department of Pharmacology, Medical College of Shaoxing University, Shaoxing, China
| | - Zheng Liu
- Department of Pharmacology, Medical College of Shaoxing University, Shaoxing, China
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23
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Voulgaris TA, Karagiannakis D, Hadziyannis E, Manolakopoulos S, Karamanolis GP, Papatheodoridis G, Vlachogiannakos J. Serum zonulin levels in patients with liver cirrhosis: Prognostic implications. World J Hepatol 2021; 13:1394-1404. [PMID: 34786174 PMCID: PMC8568570 DOI: 10.4254/wjh.v13.i10.1394] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/12/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Increased gut permeability and bacterial translocation play an important role in liver cirrhosis. Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier. AIM To investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic implications. METHODS Consecutive cirrhotic patients who attended our liver clinic were included in the study. Serum zonulin levels, clinical, radiological and biochemical data were collected at baseline. Patients who accepted participation in a regular surveillance program were followed-up for at least 12 mo. RESULTS We enrolled 116 cirrhotics [mean Child-Turcotte-Pugh (CTP) score: 6.2 ± 1.6; model for end-stage liver disease score: 11 ± 3.9]. The causes of cirrhosis were viral hepatitis (39%), alcohol (30%), non-alcoholic fatty liver disease (17%), and other (14%). At baseline, 53% had decompensated cirrhosis, 48% had ascites, and 32% had history of hepatic encephalopathy. Mean zonulin levels were significantly higher in patients with CTP-B class than CTP-A class (4.2 ± 2.4 ng/dL vs 3.5 ± 0.9 ng/dL, P = 0.038), with than without ascites (P = 0.006), and with than without history of encephalopathy (P = 0.011). Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year (P = 0.039), with an area under the receiving operating characteristic of 0.723 for predicting hepatic decompensation. Higher CTP score (P = 0.021) and portal vein diameter (P = 0.022) were independent predictors of mortality. CONCLUSION Serum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation.
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Affiliation(s)
- Theodoros A Voulgaris
- Academic Department of Gastroenterology and Hepatology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens 11527, Greece
| | - Dimitrios Karagiannakis
- Academic Department of Gastroenterology and Hepatology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens 11527, Greece
| | - E Hadziyannis
- Academic Department of Medicine, Hippokrat General Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Spilios Manolakopoulos
- Academic Department of Gastroenterology and Hepatology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens 11527, Greece
| | - Georgios P Karamanolis
- Academic Department of Gastroenterology and Hepatology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens 11527, Greece
| | - George Papatheodoridis
- Academic Department of Gastroenterology and Hepatology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens 11527, Greece
| | - John Vlachogiannakos
- Academic Department of Gastroenterology and Hepatology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens 11527, Greece.
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24
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Le Guern R, Stabler S, Gosset P, Pichavant M, Grandjean T, Faure E, Karaca Y, Faure K, Kipnis E, Dessein R. Colonization resistance against multi-drug-resistant bacteria: a narrative review. J Hosp Infect 2021; 118:48-58. [PMID: 34492304 DOI: 10.1016/j.jhin.2021.09.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 09/01/2021] [Accepted: 09/01/2021] [Indexed: 12/15/2022]
Abstract
Colonization resistance by gut microbiota is a fundamental phenomenon in infection prevention and control. Hospitalized patients may be exposed to multi-drug-resistant bacteria when hand hygiene compliance among healthcare workers is not adequate. An additional layer of defence is provided by the healthy gut microbiota, which helps clear the exogenous bacteria and acts as a safety net when hand hygiene procedures are not followed. This narrative review focuses on the role of the gut microbiota in colonization resistance against multi-drug-resistant bacteria, and its implications for infection control. The review discusses the underlying mechanisms of colonization resistance (direct or indirect), the concept of resilience of the gut microbiota, the link between the antimicrobial spectrum and gut dysbiosis, and possible therapeutic strategies. Antimicrobial stewardship is crucial to maximize the effects of colonization resistance. Avoiding unnecessary antimicrobial therapy, shortening the antimicrobial duration as much as possible, and favouring antibiotics with low anti-anaerobe activity may decrease the acquisition and expansion of multi-drug-resistant bacteria. Even after antimicrobial therapy, the resilience of the gut microbiota often occurs spontaneously. Spontaneous resilience explains the existence of a window of opportunity for colonization of multi-drug-resistant bacteria during or just after antimicrobial therapy. Strategies favouring resilience of the gut microbiota, such as high-fibre diets or precision probiotics, should be evaluated.
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Affiliation(s)
- R Le Guern
- Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille, Lille, France; Laboratoire de Bactériologie-Hygiène, CHU Lille, Lille, France.
| | - S Stabler
- Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille, Lille, France; Service de Maladies Infectieuses, CHU Lille, Lille, France
| | - P Gosset
- Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille, Lille, France
| | - M Pichavant
- Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille, Lille, France
| | - T Grandjean
- Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille, Lille, France
| | - E Faure
- Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille, Lille, France; Service de Maladies Infectieuses, CHU Lille, Lille, France
| | - Y Karaca
- Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille, Lille, France
| | - K Faure
- Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille, Lille, France; Service de Maladies Infectieuses, CHU Lille, Lille, France
| | - E Kipnis
- Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille, Lille, France; Service de Réanimation Chirurgicale, CHU Lille, Lille, France
| | - R Dessein
- Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille, Lille, France; Laboratoire de Bactériologie-Hygiène, CHU Lille, Lille, France
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25
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Van der Merwe S, Chokshi S, Bernsmeier C, Albillos A. The multifactorial mechanisms of bacterial infection in decompensated cirrhosis. J Hepatol 2021; 75 Suppl 1:S82-S100. [PMID: 34039494 DOI: 10.1016/j.jhep.2020.11.029] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 11/17/2020] [Accepted: 11/20/2020] [Indexed: 02/08/2023]
Abstract
Infections, due to a dysfunctional immune response, pose a great risk to patients with decompensated cirrhosis and herald the beginning of the terminal phase of this disease. Infections typically result from breaches in innate immune barriers and inadequate clearance by immune cells. This leads to bacterial and bacterial product translocation to the systemic circulation, which is already primed by ongoing hepatic inflammation in patients with cirrhosis, who are particularly prone to developing organ failure in the presence of an infection. Early identification of bacterial infection, along with the prompt use of appropriate antibiotics, have reduced the mortality associated with certain infections in patients with decompensated cirrhosis. Judicious use of antibiotic therapy remains imperative given the emergence of multidrug-resistant infections in the cirrhotic population. Important research over the last few years has identified molecular targets on immune cells that may enhance their function, and theoretically prevent infections. Clinical trials are ongoing to delineate the beneficial effects of targeted molecules from their off-target effects. Herein, we review the mechanisms that predispose patients with cirrhosis to bacterial infections, the clinical implications of infections and potential targets for the prevention or treatment of infections in this vulnerable population.
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Affiliation(s)
- Schalk Van der Merwe
- Department of Gastroenterology and Hepatology, University hospital, Leuven, Belgium; Laboratory of Hepatology, University of Leuven, Belgium.
| | - Shilpa Chokshi
- Institute of Hepatology, Foundation for Liver Research, London, UK; Division of Transplantation, Immunology and Mucosal Biology, Faculty of Life Sciences and Medicine, King's College, London, United Kingdom
| | - Christine Bernsmeier
- Department of Biomedicine, University of Basel, Switzerland; University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Agustin Albillos
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), CIBEREHD, Universidad de Alcalá, Madrid, Spain
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26
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Loisios-Konstantinidis I, Dressman J. Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling to Support Waivers of In Vivo Clinical Studies: Current Status, Challenges, and Opportunities. Mol Pharm 2020; 18:1-17. [PMID: 33320002 DOI: 10.1021/acs.molpharmaceut.0c00903] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling has been extensively applied to quantitatively translate in vitro data, predict the in vivo performance, and ultimately support waivers of in vivo clinical studies. In the area of biopharmaceutics and within the context of model-informed drug discovery and development (MID3), there is a rapidly growing interest in applying verified and validated mechanistic PBPK models to waive in vivo clinical studies. However, the regulatory acceptance of PBPK analyses for biopharmaceutics and oral drug absorption applications, which is also referred to variously as "PBPK absorption modeling" [Zhang et al. CPT: Pharmacometrics Syst. Pharmacol. 2017, 6, 492], "physiologically based absorption modeling", or "physiologically based biopharmaceutics modeling" (PBBM), remains rather low [Kesisoglou et al. J. Pharm. Sci. 2016, 105, 2723] [Heimbach et al. AAPS J. 2019, 21, 29]. Despite considerable progress in the understanding of gastrointestinal (GI) physiology, in vitro biopharmaceutic and in silico tools, PBPK models for oral absorption often suffer from an incomplete understanding of the physiology, overparameterization, and insufficient model validation and/or platform verification, all of which can represent limitations to their translatability and predictive performance. The complex interactions of drug substances and (bioenabling) formulations with the highly dynamic and heterogeneous environment of the GI tract in different age, ethnic, and genetic groups as well as disease states have not been yet fully elucidated, and they deserve further research. Along with advancements in the understanding of GI physiology and refinement of current or development of fully mechanistic in silico tools, we strongly believe that harmonization, interdisciplinary interaction, and enhancement of the translational link between in vitro, in silico, and in vivo will determine the future of PBBM. This Perspective provides an overview of the current status of PBBM, reflects on challenges and knowledge gaps, and discusses future opportunities around PBPK/PD models for oral absorption of small and large molecules to waive in vivo clinical studies.
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Affiliation(s)
| | - Jennifer Dressman
- Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main 60438, Germany.,Fraunhofer Institute of Translational Pharmacology and Medicine (ITMP), Carl-von-Noorden Platz 9, Frankfurt am Main 60438, Germany
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27
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GUIMARÃES VM, SANTOS VN, BORGES PSDA, DE FARIAS JLR, GRILLO P, PARISE ER. PERIPHERAL BLOOD ENDOTOXIN LEVELS ARE NOT ASSOCIATED WITH SMALL INTESTINAL BACTERIAL OVERGROWTH IN NONALCOHOLIC FATTY LIVER DISEASE WITHOUT CIRRHOSIS. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:471-476. [DOI: 10.1590/s0004-2803.202000000-82] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 08/26/2020] [Indexed: 02/07/2023]
Abstract
ABSTRACT BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease worldwide. Approximately 20% of individuals with NAFLD develop nonalcoholic steatohepatitis (NASH), which is associated with increased risk of cirrhosis, portal hypertension, and hepatocellular carcinoma. Intestinal microflora, including small intestinal bacterial overgrowth (SIBO), appear to play an important role in the pathogenesis of the disease, as demonstrated in several clinical and experimental studies, by altering intestinal permeability and allowing bacterial endotoxins to enter the circulation. OBJECTIVE: To determine the relationship between SIBO and endotoxin serum levels with clinical, laboratory, and histopathological aspects of NAFLD and the relationship between SIBO and endotoxin serum levels before and after antibiotic therapy. METHODS: Adult patients with a histological diagnosis of NAFLD, without cirrhosis were included. A comprehensive biochemistry panel, lactulose breath test (for diagnosis of SIBO), and serum endotoxin measurement (chromogenic LAL assay) were performed. SIBO was treated with metronidazole 250 mg q8h for 10 days and refractory cases were given ciprofloxacin 500 mg q12h for 10 days. RESULTS: Overall, 42 patients with a histopathological diagnosis of NAFLD were examined. The prevalence of SIBO was 26.2%. Comparison of demographic and biochemical parameters between patients with SIBO and those without SIBO revealed no statistically significant differences, except for use of proton pump inhibitors, which was significantly more frequent in patients with positive breath testing. The presence of SIBO was also associated with greater severity of hepatocellular ballooning on liver biopsy. Although the sample, as a whole, have elevated circulating endotoxin levels, we found no significant differences in this parameter between the groups with and without SIBO. Endotoxin values before and after antibiotic treatment did not differ, even on paired analysis, suggesting absence of any relationship between these factors. Serum endotoxin levels were inversely correlated with HDL levels, and directly correlated with triglyceride levels. CONCLUSION: Serum endotoxin levels did not differ between patients with and without SIBO, nor did these levels change after antibacterial therapy, virtually ruling out the possibility that elevated endotoxinemia in non-cirrhotic patients with NAFLD is associated with SIBO. Presence of SIBO was associated with greater severity of ballooning degeneration on liver biopsy, but not with a significantly higher prevalence of NASH. Additional studies are needed to evaluate the reproducibility and importance of this finding in patients with NAFLD and SIBO.
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28
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Current Status and Prospects of Spontaneous Peritonitis in Patients with Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3743962. [PMID: 32724800 PMCID: PMC7364234 DOI: 10.1155/2020/3743962] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 06/03/2020] [Indexed: 12/14/2022]
Abstract
Spontaneous bacterial peritonitis (SBP) is a common cirrhotic ascites complication which exacerbates the patient's condition. SBP is caused by gram-negative bacilli and, to a lesser extent, gram-positive cocci. Hospital-acquired infections show higher levels of drug-resistant bacteria. Geographical location influences pathogenic bacteria distribution; therefore, different hospitals in the same country record different bacteria strains. Intestinal changes and a weak immune system in patients with liver cirrhosis lead to bacterial translocation thus causing SBP. Early diagnosis and timely treatment are important in SBP management. When the treatment effect is not effective, other rare pathogens should be explored.
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29
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Gundling F, Luxi M, Seidel H, Schepp W, Schmidt T. Small intestinal dysmotility in cirrhotic patients: correlation with severity of liver disease and cirrhosis-associated complications. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 59:540-550. [PMID: 32512591 DOI: 10.1055/a-1162-0357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
INTRODUCTION Altered small intestinal motility has been observed in various manometry studies in patients with cirrhosis. Since small bowel manometry is available only in a few centers, interpretation of dysmotility in cirrhosis is controversial. PATIENTS AND METHODS In this study, both fasting and postprandial manometric tracings of 24-hour antroduodenojejunal manometries were analyzed using both visual analysis and computer-aided analysis. RESULTS In 34 patients (83 %), the mean migrating motor complex (MMC) cycle length was different compared with healthy controls. Phase II was prolonged in 27 patients (66 %), while phase I showed a reduced duration in 23 (56 %) and in phase III in 13 individuals (32 %). We also observed special motor patterns, e. g., migrating clustered contractions (MCCs) or retrograde clustered contractions (RCCs), which were present during fasting (69 %) and postprandial (92 %) motility, while none of the healthy controls showed any special motor patterns. Special motor patterns showed a significant correlation with the severity of cirrhosis (Child-Score; p > 0.05) and the existence of ascites (p < 0.05). DISCUSSION This study in a large cohort of patients with cirrhosis by using 24-hour, solid state portable manometry showed in most individuals disturbances of cyclic fasting motility. Special motor patterns like RCCs during fasting and postprandial motility could be observed exclusively in the cirrhosis group, showing a significant correlation with severity of cirrhosis and the occurence of associated complications.
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Affiliation(s)
- Felix Gundling
- Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Munich, Germany.,Department of Internal Medicine - Division of Gastroenterology, Diabetology and Endocrinology, Kemperhof Koblenz, Koblenz, Germany
| | - Margo Luxi
- Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Munich, Germany
| | - Holger Seidel
- Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Munich, Germany.,Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Isar Klinik, Munich, Germany
| | - Wolfgang Schepp
- Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Munich, Germany
| | - Thomas Schmidt
- Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Munich, Germany.,Helios Klinik Attendorn, Attendorn, Germany
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30
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Li B, Gao Y, Wang X, Qian Z, Meng Z, Huang Y, Deng G, Lu X, Liu F, Zheng X, Li H, Chen J. Clinical features and outcomes of bacterascites in cirrhotic patients: A retrospective, multicentre study. Liver Int 2020; 40:1447-1456. [PMID: 32128975 DOI: 10.1111/liv.14418] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 02/02/2020] [Accepted: 02/19/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Current guidelines on the management of bacterascites are limited. This multicentre, retrospective study investigated the clinical features and outcomes of cirrhosis patients with bacterascites. METHODS Two series of cirrhosis patients were evaluated. The first included 418 patients with ascites-positive cultures at 11 hospitals during 2012-2018. Clinical characteristics and outcomes were recorded. The second included 208 patients with sterile ascites from a prospective cohort (NCT02457637). Clinical features and outcomes of cirrhotic patients with or without bacterascites were investigated. RESULTS In the first series, bacterascites was diagnosed in 254/418 (60.8%) patients, and culture-positive spontaneous bacterial peritonitis (SBP) in 164/418 (39.2%) patients. Gram-positive bacteria were more prevalent in bacterascites patients than in culture-positive SBP patients (59.1% vs 22.0%; P < .001). For patients with acute-on-chronic liver failure (ACLF) in bacterascites and culture-positive SBP groups, the 28-day transplant-free mortality (41.3% vs 65.5%; P = .015) and the prevalence of in-hospital acute kidney injury (AKI) (84.8% vs 75%; P = .224). For patients without ACLF in the bacterascites (n = 208) and culture-positive SBP groups (n = 108), the 28-day transplant-free mortalities were 13% vs 13.9% (P = .822), the probabilities of progression to ACLF within 28 days were 10.1% vs 14.8% (P = .216) and the prevalences of in-hospital AKI were 14.4% vs 30.6% (P = .001). Bacterascites patients had higher 28-day mortality than those patients with sterile ascites, after propensity score matching (18.4% vs 8.6%; P = .010). CONCLUSION Bacterascites patients had non-negligible poor clinical outcomes, including in-hospital AKI, progression to ACLF and 28-day mortality. Future studies are warranted to expedite the diagnosis of bacterascites and optimize antibiotic treatment.
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Affiliation(s)
- Beiling Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yanhang Gao
- Department of Hepatology, The First Hospital of Jilin University (JU), Jilin, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Zhiping Qian
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre (SPHCC), Fudan University, Shanghai, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Zhongji Meng
- Department of Infectious Diseases, Taihe Hospital, Hubei University of Medicine, Hubei, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Yan Huang
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Hunan, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Guohong Deng
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Xiaobo Lu
- Infectious Disease Centre, The First Affiliated Hospital of Xinjiang Medical University (XMU), Xinjiang, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Feng Liu
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University (SDU), Jinan, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Xin Zheng
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Hai Li
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
| | - Jinjun Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Chinese (acute on) Chronic Liver Failure Consortium (Ch-CLIF.C), China
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Wijarnpreecha K, Werlang ME, Watthanasuntorn K, Panjawatanan P, Cheungpasitporn W, Gomez V, Lukens FJ, Ungprasert P. Obesity and Risk of Small Intestine Bacterial Overgrowth: A Systematic Review and Meta-Analysis. Dig Dis Sci 2020; 65:1414-1422. [PMID: 31605277 DOI: 10.1007/s10620-019-05887-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 10/09/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND/OBJECTIVES Recent studies have proposed that obesity may be associated with a higher risk of small intestine bacterial overgrowth (SIBO) although the results were inconsistent. The microbiome has a known metabolic role; its impact on obesity in animal models generated the hypothesis of an association between a dysfunctional microbiome and obesity. We performed this systematic review and meta-analysis to elucidate this possible association by summarizing all available data. METHODS A literature search utilizing MEDLINE and EMBASE databases from inception until August 2019 was conducted. Eligible studies included either cohort studies or cross-sectional studies that consisted of two groups of participants, those with obesity and those without obesity, and compared the prevalence of SIBO between the groups. Adjusted odds ratios (OR) from each study were consolidated by the generic inverse variance method of DerSimonian and Laird. RESULTS A total of five studies with 515 patients fulfilled eligibility criteria and were included in this meta-analysis. The risk of SIBO among individuals with obesity was higher than in individuals without obesity but did not reach statistical significance with a pooled OR of 2.08 [95% confidence interval (CI) 0.82-5.31; p = 0.12; I2 84%]. Sensitivity analysis including only studies from Western countries increased the pooled OR to 3.41 and reached statistical significance (95% CI 1.21-9.59; p = 0.02; I2 62%). CONCLUSIONS This meta-analysis found that the risk of SIBO was about two times higher among individuals with obesity compared to individuals without obesity, although the result did not reach statistical significance. The risk increased to threefold and reached statistical significance when only studies from Western countries were included. These observations may suggest the role of obesity as a predisposing factor for SIBO although more studies are still needed to corroborate these preliminary results.
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Affiliation(s)
- Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA.
| | - Monia E Werlang
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA
| | | | | | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
| | - Victoria Gomez
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA
| | - Frank J Lukens
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA
| | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Roehlen N, Crouchet E, Baumert TF. Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells 2020; 9:cells9040875. [PMID: 32260126 PMCID: PMC7226751 DOI: 10.3390/cells9040875] [Citation(s) in RCA: 700] [Impact Index Per Article: 140.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 03/28/2020] [Accepted: 04/01/2020] [Indexed: 02/06/2023] Open
Abstract
Liver fibrosis due to viral or metabolic chronic liver diseases is a major challenge of global health. Correlating with liver disease progression, fibrosis is a key factor for liver disease outcome and risk of hepatocellular carcinoma (HCC). Despite different mechanism of primary liver injury and disease-specific cell responses, the progression of fibrotic liver disease follows shared patterns across the main liver disease etiologies. Scientific discoveries within the last decade have transformed the understanding of the mechanisms of liver fibrosis. Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. However, reversal often occurs too slowly or too infrequent to avoid life-threatening complications particularly in advanced fibrosis. Thus, there is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and HCC development. However, while many anti-fibrotic candidate agents have shown robust effects in experimental animal models, their anti-fibrotic effects in clinical trials have been limited or absent. Thus, no approved therapy exists for liver fibrosis. In this review we summarize cellular drivers and molecular mechanisms of fibrogenesis in chronic liver diseases and discuss their impact for the development of urgently needed anti-fibrotic therapies.
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Affiliation(s)
- Natascha Roehlen
- Université de Strasbourg, 67000 Strasbourg, France; (N.R.); (E.C.)
- Institut de Recherche sur les Maladies Virales et Hépatiques U1110, 67000 Strasbourg, France
| | - Emilie Crouchet
- Université de Strasbourg, 67000 Strasbourg, France; (N.R.); (E.C.)
- Institut de Recherche sur les Maladies Virales et Hépatiques U1110, 67000 Strasbourg, France
| | - Thomas F. Baumert
- Université de Strasbourg, 67000 Strasbourg, France; (N.R.); (E.C.)
- Institut de Recherche sur les Maladies Virales et Hépatiques U1110, 67000 Strasbourg, France
- Pôle Hepato-digestif, Institut Hopitalo-Universitaire, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France
- Correspondence: ; Tel.: +33-366853703
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Arab JP, Arrese M, Shah VH. Gut microbiota in non-alcoholic fatty liver disease and alcohol-related liver disease: Current concepts and perspectives. Hepatol Res 2020; 50:407-418. [PMID: 31840358 PMCID: PMC7187400 DOI: 10.1111/hepr.13473] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 12/05/2020] [Accepted: 12/10/2020] [Indexed: 12/17/2022]
Abstract
The term, gut-liver axis, is used to highlight the close anatomical and functional relationship between the intestine and the liver. It has been increasingly recognized that the gut-liver axis plays an essential role in the development and progression of liver disease. In particular, in non-alcoholic fatty liver disease and alcohol-related liver disease, the two most common causes of chronic liver disease, a dysbiotic gut microbiota can influence intestinal permeability, allowing some pathogens or bacteria-derived factors from the gut reaching the liver through the enterohepatic circulation contributing to liver injury, steatohepatitis, and fibrosis progression. Pathways involved are multiple, including changes in bile acid metabolism, intestinal ethanol production, generation of short-chain fatty acids, and other by-products. Bile acids act through dedicated bile acid receptors, farnesoid X receptor and TGR5, in both the ileum and the liver, influencing lipid metabolism, inflammation, and fibrogenesis. Currently, both non-alcoholic fatty liver disease and alcohol-related liver disease lack effective therapies, and therapeutic targeting of gut microbiota and bile acids enterohepatic circulation holds promise. In this review, we summarize current knowledge about the role of gut microbiota in the pathogenesis of non-alcoholic fatty liver disease and alcohol-related liver disease, as well as the relevance of microbiota or bile acid-based approaches in the management of those liver diseases.
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Affiliation(s)
- Juan P. Arab
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.,Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile,Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Albillos A, de Gottardi A, Rescigno M. The gut-liver axis in liver disease: Pathophysiological basis for therapy. J Hepatol 2020; 72:558-577. [PMID: 31622696 DOI: 10.1016/j.jhep.2019.10.003] [Citation(s) in RCA: 1201] [Impact Index Per Article: 240.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 09/14/2019] [Accepted: 10/02/2019] [Indexed: 02/06/2023]
Abstract
The gut-liver axis refers to the bidirectional relationship between the gut and its microbiota, and the liver, resulting from the integration of signals generated by dietary, genetic and environmental factors. This reciprocal interaction is established by the portal vein which enables transport of gut-derived products directly to the liver, and the liver feedback route of bile and antibody secretion to the intestine. The intestinal mucosal and vascular barrier is the functional and anatomical structure that serves as a playground for the interactions between the gut and the liver, limiting the systemic dissemination of microbes and toxins while allowing nutrients to access the circulation and to reach the liver. The control of microbial communities is critical to maintaining homeostasis of the gut-liver axis, and as part of this bidirectional communication the liver shapes intestinal microbial communities. Alcohol disrupts the gut-liver axis at multiple interconnected levels, including the gut microbiome, mucus barrier, epithelial barrier and at the level of antimicrobial peptide production, which increases microbial exposure and the proinflammatory environment of the liver. Growing evidence indicates the pathogenetic role of microbe-derived metabolites, such as trimethylamine, secondary bile acids, short-chain fatty acids and ethanol, in the pathogenesis of non-alcoholic fatty liver disease. Cirrhosis by itself is associated with profound alterations in gut microbiota and damage at the different levels of defence of the intestinal barrier, including the epithelial, vascular and immune barriers. The relevance of the severe disturbance of the intestinal barrier in cirrhosis has been linked to translocation of live bacteria, bacterial infections and disease progression. The identification of the elements of the gut-liver axis primarily damaged in each chronic liver disease offers possibilities for intervention. Beyond antibiotics, upcoming therapies centred on the gut include new generations of probiotics, bacterial metabolites (postbiotics), faecal microbial transplantation, and carbon nanoparticles. FXR-agonists target both the gut and the liver and are currently being tested in different liver diseases. Finally, synthetic biotic medicines, phages that target specific bacteria or therapies that create physical barriers between the gut and the liver offer new therapeutic approaches.
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Affiliation(s)
- Agustín Albillos
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, IRYCIS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
| | - Andrea de Gottardi
- Hepatology, Inselspital and Department of Biomedical Research, University of Bern, Switzerland; Servizio di Gastroenterología e Epatologia, Ente Ospedaliero Cantonale, Università della Svizzera Italiana, Lugano, Switzerland
| | - María Rescigno
- Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele (Mi), Italy; Humanitas Clinical and Research Center, IRCCS, 20089 Rozzano (Mi), Italy
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35
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Liu Chen Kiow J, Vincent C, Sidani S, Bouin M. High occurrence of small intestinal bacterial overgrowth in primary biliary cholangitis. Neurogastroenterol Motil 2019; 31:e13691. [PMID: 31373141 DOI: 10.1111/nmo.13691] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 07/11/2019] [Accepted: 07/18/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease affecting mainly middle-aged women. An alteration in intestinal motility has been well documented in cirrhosis predisposing to small intestinal bacterial overgrowth (SIBO). Patients with PBC frequently complain of various gastrointestinal symptoms compatible with SIBO. No study has specifically been published to this day to determine the occurrence of SIBO in PBC. Our objective was to determine the prevalence of SIBO in patients with PBC. METHODS Retrospective study from 2010 to 2018. All patients diagnosed with PBC during this period had a systematic screening for SIBO in their diagnostic workup. The diagnosis of SIBO was made by a carbohydrate breath test (lactulose and/or glucose). Clinical and paraclinical factors of patients were compared with a control group of healthy subjects. KEY RESULTS Ninety-eight subjects were included in the study (mean age 49, range 21-88 years) including 58 patients with PBC and 40 healthy subjects. The PBC group was older than the control group (mean age 56, range 31-88 vs 39, range 21-62 years; P < .001), but identical for gender and body mass index. The prevalence of SIBO was higher in PBC versus controls (32.8% vs 2.5%; P < .001). The PBC group with SIBO had significantly more diarrhea (78.9% vs 35.9%; P < .05) than the PBC group without SIBO, but the prevalence of abdominal pain and bloating was similar. CONCLUSIONS & INFERENCES The high occurrence of SIBO in PBC may explain some of the frequently reported gastrointestinal symptoms. This study justifies the systematic screening for SIBO in PBC.
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Affiliation(s)
- Jeremy Liu Chen Kiow
- Department of Gastroenterology and Hepatology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada
| | - Catherine Vincent
- Department of Gastroenterology and Hepatology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada
| | - Sacha Sidani
- Department of Gastroenterology and Hepatology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada
| | - Mickael Bouin
- Department of Gastroenterology and Hepatology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada
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37
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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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38
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Iacob S, Iacob DG. Infectious Threats, the Intestinal Barrier, and Its Trojan Horse: Dysbiosis. Front Microbiol 2019; 10:1676. [PMID: 31447793 PMCID: PMC6692454 DOI: 10.3389/fmicb.2019.01676] [Citation(s) in RCA: 87] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 07/08/2019] [Indexed: 02/06/2023] Open
Abstract
The ecosystem of the gut microbiota consists of diverse intestinal species with multiple metabolic and immunologic activities and it is closely connected with the intestinal epithelia and mucosal immune response, with which it builds a complex barrier against intestinal pathogenic bacteria. The microbiota ensures the integrity of the gut barrier through multiple mechanisms, either by releasing antibacterial molecules (bacteriocins) and anti-inflammatory short-chain fatty acids or by activating essential cell receptors for the immune response. Experimental studies have confirmed the role of the intestinal microbiota in the epigenetic modulation of the gut barrier through posttranslational histone modifications and regulatory mechanisms induced by epithelial miRNA in the epithelial lumen. Any quantitative or functional changes of the intestinal microbiota, referred to as dysbiosis, alter the immune response, decrease epithelial permeability and destabilize intestinal homeostasis. Consequently, the overgrowth of pathobionts (Staphylococcus, Pseudomonas, and Escherichia coli) favors intestinal translocations with Gram negative bacteria or their endotoxins and could trigger sepsis, septic shock, secondary peritonitis, or various intestinal infections. Intestinal infections also induce epithelial lesions and perpetuate the risk of bacterial translocation and dysbiosis through epithelial ischemia and pro-inflammatory cytokines. Furthermore, the decline of protective anaerobic bacteria (Bifidobacterium and Lactobacillus) and inadequate release of immune modulators (such as butyrate) affects the release of antimicrobial peptides, de-represses microbial virulence factors and alters the innate immune response. As a result, intestinal germs modulate liver pathology and represent a common etiology of infections in HIV immunosuppressed patients. Antibiotic and antiretroviral treatments also promote intestinal dysbiosis, followed by the selection of resistant germs which could later become a source of infections. The current article addresses the strong correlations between the intestinal barrier and the microbiota and discusses the role of dysbiosis in destabilizing the intestinal barrier and promoting infectious diseases.
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Affiliation(s)
- Simona Iacob
- Infectious Diseases Department, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.,National Institute of Infectious Diseases "Prof. Dr. Matei Balş", Bucharest, Romania
| | - Diana Gabriela Iacob
- Infectious Diseases Department, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
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The Effect of Obesity on the Quality of Bowel Preparation for Colonoscopy: Results From a Large Observational Study. J Clin Gastroenterol 2019; 53:e214-e220. [PMID: 29738352 DOI: 10.1097/mcg.0000000000001045] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Obesity has been linked to suboptimal bowel preparation but this association has not been conclusively investigated in prospective studies. GOALS Our objective was to determine whether any relationship exists between obesity as measured by body mass index (BMI) and quality of bowel preparation. STUDY Adult patients who presented for outpatient colonoscopy at a single urban ambulatory surgery center within a 6-month period and fulfilled inclusion criteria were prospectively enrolled for the study. Patients were divided by BMI into subcategories based on the World Health Organization international classification of obesity. The Modified Aronchick scale was used to assess bowel preparation for colonoscopy. A univariate and multivariate analysis was used to determine a possible association between BMI and poor preparation. RESULTS A total of 1429 patients were evaluated. On the basis of inclusion criteria, 1314 subjects were analyzed, out of which 73% were overweight or obese. Inadequate bowel preparation was noted in 21.1% of patients. There was no correlation between obesity and the quality of the bowel preparation. Male gender (P=0.002), diabetes mellitus (P<0.0001), liver cirrhosis (P=0.001), coronary artery disease (P=0.003), refractory constipation (P<0.0001), and current smoking (P=0.01) were found to be independently predictive of poor bowel preparation. CONCLUSIONS Increased BMI is not predictive of suboptimal bowel preparation for colonoscopy. The results of our study are pivotal given the increased risk of colorectal cancer in obese patients and their known lower rate of colorectal cancer screening in certain populations. It is important to avoid subjecting these patients to an intensive bowel preparation that may further discourage screening in a patient population that requires it.
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40
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Baffy G. Potential mechanisms linking gut microbiota and portal hypertension. Liver Int 2019; 39:598-609. [PMID: 30312513 DOI: 10.1111/liv.13986] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 10/01/2018] [Accepted: 10/04/2018] [Indexed: 12/11/2022]
Abstract
Gut microbiota is the largest collection of commensal micro-organisms in the human body, engaged in reciprocal cellular and molecular interactions with the liver. This mutually beneficial relationship may break down and result in dysbiosis, associated with disease phenotypes. Altered composition and function of gut microbiota has been implicated in the pathobiology of nonalcoholic fatty liver disease (NAFLD), a prevalent condition linked to obesity, insulin resistance and endothelial dysfunction. NAFLD may progress to cirrhosis and portal hypertension, which is the result of increased intrahepatic vascular resistance and altered splanchnic circulation. Gut microbiota may contribute to rising portal pressure from the earliest stages of NAFLD, although the significance of these changes remains unclear. NAFLD has been linked to lower microbial diversity and weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defence and inflammation. Moreover, disrupted host-microbial metabolic interplay alters bile acid signalling and the release of vasoregulatory gasotransmitters. These perturbations become prominent in cirrhosis, increasing the risk of clinically significant portal hypertension and leading to bacterial translocation, sepsis and acute-on-chronic liver failure. Better understanding of the gut-liver axis and identification of novel microbial molecular targets may yield specific strategies in the prevention and management of portal hypertension.
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Affiliation(s)
- Gyorgy Baffy
- Department of Medicine, VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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41
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Jiang JW, Chen XH, Ren Z, Zheng SS. Gut microbial dysbiosis associates hepatocellular carcinoma via the gut-liver axis. Hepatobiliary Pancreat Dis Int 2019; 18:19-27. [PMID: 30527903 DOI: 10.1016/j.hbpd.2018.11.002] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 09/28/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Gut microbiota has been demonstrated to play a critical role in liver inflammation, chronic fibrosis, liver cirrhosis, and HCC development through the gut-liver axis. DATA SOURCES Recently there have been several innovative studies investigating gut microbial dysbiosis-mediated enhancement of HCC through the gut-liver axis. Literatures from January 1998 to January 2018 were searched in the PubMed database using the keywords "gut microbiota" and "hepatocellular carcinoma" or "liver cancer", and the results of experimental and clinical studies were analyzed. RESULTS Gut microbial dysbiosis accompanies the progression of alcoholic liver disease, non-alcoholic fatty liver disease and liver cirrhosis, and promotes HCC progression in an experimental mouse model. The immune system and key factors such as Toll-like receptor 4 are involved in the process. There is evidence for gut microbial dysbiosis in hepatitis virus-related HCC patients. CONCLUSIONS Gut microbial dysbiosis is closely associated with hepatic inflammation disease and HCC through the gut-liver axis. With the enhanced understanding of the interactions between gut microbiota and liver through the gut-liver axis, new treatment strategies for HCC are being developed.
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Affiliation(s)
- Jian-Wen Jiang
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Road, Hangzhou 310003, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China; Health Management Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xin-Hua Chen
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Road, Hangzhou 310003, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China
| | - Zhigang Ren
- Department of Infectious Disease, Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Road, Hangzhou 310003, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
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Buerger AN, Schmidt J, Chase A, Paixao C, Patel TN, Brumback BA, Kane AS, Martyniuk CJ, Bisesi JH. Examining the responses of the zebrafish (Danio rerio) gastrointestinal system to the suspected obesogen diethylhexyl phthalate. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2019; 245:1086-1094. [PMID: 30682743 DOI: 10.1016/j.envpol.2018.11.032] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 10/26/2018] [Accepted: 11/09/2018] [Indexed: 06/09/2023]
Abstract
Epidemiological evidence suggests that phthalate plasticizers may act as "obesogens", which are chemicals that exacerbate obesity. The gastrointestinal (GI) system is the primary exposure route for phthalates, however, the relationship between phthalate-driven perturbations of GI system functions that can influence obesity has yet to be examined. To address this knowledge gap, we exposed Danio rerio (zebrafish) for 60 days to either (1) Control feeding (5 mg/fish/day), (2) Overfeeding (20 mg/fish/day) or (3) Overfeeding with diethyl-hexyl phthalate (DEHP) (20 mg/fish/day with 3 mg/kg DEHP). After 60 days, Overfed and Overfed + DEHP zebrafish had elevated body mass, and hepatosomatic and gonadosomatic indices. RNAseq analysis of the GI revealed enrichment of gene networks related to lipid metabolism in the Overfed + DEHP group. Many of the enriched networks were under transcriptional control of peroxisome proliferator activated receptor alpha (pparα), a known modulator of lipid metabolism, immune function, and GI function. Real-time PCR confirmed that pparα was overexpressed in the Overfed + DEHP zebrafish, further revealing a pathway by which DEHP may influence lipid metabolism via the GI. These data increase our understanding of phthalate-driven effects on GI function and lipid metabolism, identifying gut-specific gene networks that may drive phthalate-exacerbated obesity.
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Affiliation(s)
- Amanda N Buerger
- Department of Environmental and Global Health, University of Florida, Gainesville, FL, 32611, USA; Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611, USA
| | - Jordan Schmidt
- Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611, USA; Department of Physiological Sciences, UF Genetics Institute, University of Florida, Gainesville, FL, 32611, USA
| | - Amanda Chase
- Department of Environmental and Global Health, University of Florida, Gainesville, FL, 32611, USA; Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611, USA
| | - Carla Paixao
- Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611, USA; Department of Physiological Sciences, UF Genetics Institute, University of Florida, Gainesville, FL, 32611, USA
| | - Tejas N Patel
- Department of Environmental and Global Health, University of Florida, Gainesville, FL, 32611, USA; Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611, USA
| | - Babette A Brumback
- Department of Biostatistics, University of Florida, Gainesville, FL, 32611, USA
| | - Andrew S Kane
- Department of Environmental and Global Health, University of Florida, Gainesville, FL, 32611, USA; Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611, USA; Emerging Pathogens Institute, University of Florida, Gainesville, FL, 32611, USA
| | - Christopher J Martyniuk
- Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611, USA; Department of Physiological Sciences, UF Genetics Institute, University of Florida, Gainesville, FL, 32611, USA
| | - Joseph H Bisesi
- Department of Environmental and Global Health, University of Florida, Gainesville, FL, 32611, USA; Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611, USA.
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43
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Abstract
Malnutrition is a change in body composition owing to disordered nutrition associated with a decrease in function and poor clinical outcomes. Malnutrition can result from overnutrition, undernutrition and inflammatory activity. Patients with alcoholic liver disease are at increased risk for malnutrition. In this article, we discuss the different methods used to assess malnutrition, prevalence of malnutrition, potential mechanisms underlying malnutrition, and its treatments in patients with alcoholic liver disease.
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Affiliation(s)
- Brett Styskel
- Section of Gastroenterology and Hepatology, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX 77030, USA
| | - Yamini Natarajan
- Section of Gastroenterology and Hepatology, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX 77030, USA.
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX 77030, USA; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA; Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
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Dumic I, Nordin T, Jecmenica M, Stojkovic Lalosevic M, Milosavljevic T, Milovanovic T. Gastrointestinal Tract Disorders in Older Age. Can J Gastroenterol Hepatol 2019; 2019:6757524. [PMID: 30792972 PMCID: PMC6354172 DOI: 10.1155/2019/6757524] [Citation(s) in RCA: 134] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 12/11/2018] [Accepted: 12/17/2018] [Indexed: 02/07/2023] Open
Abstract
Considering an increase in the life expectancy leading to a rise in the elderly population, it is important to recognize the changes that occur along the process of aging. Gastrointestinal (GI) changes in the elderly are common, and despite some GI disorders being more prevalent in the elderly, there is no GI disease that is limited to this age group. While some changes associated with aging GI system are physiologic, others are pathological and particularly more prevalent among those above age 65 years. This article reviews the most important GI disorders in the elderly that clinicians encounter on a daily basis. We highlight age-related changes of the oral cavity, esophagus, stomach, small and large bowels, and the clinical implications of these changes. We review epidemiology and pathophysiology of common diseases, especially as they relate to clinical manifestation in elderly. Details regarding management of specific disease are discussed in detail if they significantly differ from the management for younger groups or if they are associated with significant challenges due to side effects or polypharmacy. Cancers of GI tract are not included in the scope of this article.
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Affiliation(s)
- Igor Dumic
- Division of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI, USA
- Mayo Clinic College of Medicine and Sciences, Rochester, MN, USA
| | - Terri Nordin
- Mayo Clinic College of Medicine and Sciences, Rochester, MN, USA
- Department of Family Medicine, Mayo Clinic Health System, Eau Claire WI, USA
| | - Mladen Jecmenica
- Gastroenterology Fellowship Program, The Wright Center for Graduate Medical Education, Scranton, PA, USA
| | | | - Tomica Milosavljevic
- Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, Belgrade University, Belgrade, Serbia
| | - Tamara Milovanovic
- Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade, Serbia
- School of Medicine, Belgrade University, Belgrade, Serbia
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45
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Milosevic I, Vujovic A, Barac A, Djelic M, Korac M, Radovanovic Spurnic A, Gmizic I, Stevanovic O, Djordjevic V, Lekic N, Russo E, Amedei A. Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature. Int J Mol Sci 2019; 20:395. [PMID: 30658519 PMCID: PMC6358912 DOI: 10.3390/ijms20020395] [Citation(s) in RCA: 330] [Impact Index Per Article: 55.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Revised: 01/13/2019] [Accepted: 01/14/2019] [Indexed: 02/06/2023] Open
Abstract
The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called "the new virtual metabolic organ", makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of "ancient" microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies.
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Affiliation(s)
- Ivana Milosevic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Ankica Vujovic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Aleksandra Barac
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Marina Djelic
- Faculty of Medicine, Universisty of Belgrade; Institute of Medical Physiology "Rihard Burijan", 11000 Belgrade, Serbia.
| | - Milos Korac
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Aleksandra Radovanovic Spurnic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Ivana Gmizic
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Olja Stevanovic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Hospital for Infectious and Tropical Diseases, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Vladimir Djordjevic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Clinic for Digestive Surgery, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Nebojsa Lekic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
- Clinic for Digestive Surgery, Clinical Center of Serbia, 11000 Belgrade, Serbia.
| | - Edda Russo
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
- Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), 50134 Florence, Italy.
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46
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Arunima A, Das JK, Suar M. Gut Microbes in Liver Diseases. DIETARY INTERVENTIONS IN GASTROINTESTINAL DISEASES 2019:117-131. [DOI: 10.1016/b978-0-12-814468-8.00010-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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47
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Ghosh G, Jesudian AB. Small Intestinal Bacterial Overgrowth in Patients With Cirrhosis. J Clin Exp Hepatol 2019; 9:257-267. [PMID: 31024208 PMCID: PMC6477138 DOI: 10.1016/j.jceh.2018.08.006] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 08/19/2018] [Indexed: 02/07/2023] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is defined by increased density and/or abnormal composition of microbiota in the small bowel. SIBO is often encountered in patients with cirrhosis as a result of impaired intestinal motility and delayed transit time, both of which are exacerbated by more severe liver disease. Additional risk factors for SIBO commonly encountered in cirrhotic patients include coexisting diabetes, autonomic neuropathy, and/or alcoholic use. Diagnosis of SIBO is performed by breath testing or jejunal aspiration, the gold standard. In cirrhotic patients, the presence of SIBO can lead to profound clinical consequences. Increased intestinal permeability in these patients predisposes to bacterial translocation into the systemic circulation. As a result, SIBO is implicated as a significant risk factor in the pathogenesis of both spontaneous bacterial peritonitis and hepatic encephalopathy in cirrhotics. Antibiotics, especially rifaximin, are the best studied and most effective treatment options for SIBO. However, prokinetics, probiotics, nonselective beta-blockers, and treatment of underlying liver-related pathophysiology with transjugular intrahepatic portosystemic shunt placement or liver transplantation are also being investigated. This review will discuss the risk factors, diagnosis, manifestations in cirrhosis, and treatment options of SIBO.
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Key Words
- 51Cr-EDTA, 51Cr-Ethylenediaminetetraacetic Acid
- CFUs, Colony-Forming Units
- CP, Child-Pugh Score
- FODMAPS, Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols
- GI, Gastrointestinal
- HBV, Hepatitis B Virus
- HE, Hepatic Encephalopathy
- IBS, Irritable Bowel Syndrome
- MHE, Minimal Hepatic Encephalopathy
- MMC, Migrating Motor Complex
- OCTT, Orocecal Transit Time
- PH, Portal Hypertension
- PPI, Proton Pump Inhibitor
- SBP, Spontaneous Bacterial Peritonitis
- SBRT, Small Bowel Residence Time
- SBTT, Small Bowel Transit Time
- SIBO, Small Intestinal Bacterial Overgrowth
- TIPS, Transjugular Intrahepatic Portosystemic Shunt
- bacterial translocation
- cirrhosis
- liver disease
- mL, Milliliter
- ppm, Parts Per Million
- small intestinal bacterial overgrowth
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Affiliation(s)
- Gaurav Ghosh
- Department of Medicine, NewYork-Presbyterian Hospital/Weill Cornell Medicine, 525 E. 68th Street, M-532, New York, NY, 10065, USA
| | - Arun B. Jesudian
- Division of Gastroenterology and Hepatology, NewYork-Presbyterian Hospital/Weill Cornell Medicine, 1305 York Avenue, 4th Floor, New York, NY, 10065, USA,Address for correspondence: Arun B. Jesudian, 1305 York Avenue, 4th Floor, New York, NY, 10065, USA
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48
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Bjerring PN, Morgan MY, Vilstrup H, Nielsen SM, Christensen R, Gluud LL. Medical interventions for prevention and treatment of hepatic encephalopathy in adults with cirrhosis: a network meta‐analysis. Cochrane Database Syst Rev 2018; 2018:CD013241. [PMCID: PMC6517127 DOI: 10.1002/14651858.cd013241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the beneficial and harmful effects of medical interventions for prevention and treatment of hepatic encephalopathy in adults with cirrhosis.
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Affiliation(s)
- Peter N Bjerring
- Copenhagen University Hospital HvidovreGastrounit, Medical DivisionHvidovreDenmark
| | - Marsha Y Morgan
- Division of Medicine, Royal Free Campus, University College LondonUCL Institute for Liver & Digestive HealthRowland Hill StreetHampsteadLondonUKNW3 2PF
| | - Hendrik Vilstrup
- Aarhus University HospitalDepartment of Hepatology and GastroenterologyNørrebrogade 44AarhusDenmark
| | - Sabrina M Nielsen
- The Parker Institute, Bispebjerg and Frederiksberg HospitalMusculoskeletal Statistics UnitCopenhagenDenmark2000 F
| | - Robin Christensen
- Bispebjerg and Frederiksberg HospitalMusculoskeletal Statistics Unit, The Parker InstituteCopenhagenDenmark
| | - Lise Lotte Gluud
- Copenhagen University Hospital HvidovreGastrounit, Medical DivisionHvidovreDenmark
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49
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is an increasingly important cause of chronic liver disease globally. Similar to metabolic syndrome and obesity, NAFLD is associated with alternations in the gut microbiota and its related biological pathways. While the exact pathophysiology of NAFLD remains largely unknown, changes in intestinal inflammation, gut permeability, energy harvest, anaerobic fermentation and insulin resistance have been described. In this chapter, we review the relationship between the gut microbiota, obesity and NAFLD, and highlight potential ways to modify the gut microbiota to help managing NAFLD patients.
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Affiliation(s)
- Louis H S Lau
- Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Department of Medicine & Therapeutics and LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Sunny H Wong
- Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Department of Medicine & Therapeutics and LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
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50
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Tu B, Bi J, Wu D, Zhao P, Shi L, Xie Y, Zhang X, Xu Z, Liu S, Wang X, Li X, Wang F, Qin E. Bloodstream infection due to Escherichia coli in liver cirrhosis patients: clinical features and outcomes. Oncotarget 2018; 9:35780-35789. [PMID: 30515269 PMCID: PMC6254670 DOI: 10.18632/oncotarget.23200] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Accepted: 05/29/2017] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES The study aimed to investigate the clinical characteristics and antibiotic management, as well as independent indicators for survival within 30 days for Escherichia coli bloodstream infection (BSI) in liver cirrhosis. RESULTS Hospital-acquired BSI accounted for 60.07%, with prolonged hospital stay (P = 0.000). The prevalence of Extended Spectrum Beta-Lactamases (ESBL) producing bacteria was 48.26%, which correlated with ICU admission (P = 0.015) and high model for end-stage liver disease (MELD) score at onset of BSI (P = 0.035). Moreover, ESBL producing pathogens showed a high resistant to the common antibiotic families and 27.5% pathogens were confirmed as multidrug-resistant (MDR). MDR infection was significantly correlated with ESBL production, ICU admission, inappropriate empiric therapy, resistance to firstly selected antibiotic, and infection duration (P < 0.05 for all). In addition, appropriate empiric therapy within 48 h (HR = 2.581, 95% CI = 1.166-5.715), ICU admission (HR = 4.434, 95% CI = 2.130-8.823), HE (HR = 2.379, 95% CI = 1.115-5.073) and final MELD (HR = 1.074, 95% CI = 1.044-1.106) were independent indicators for 30-day mortality. MATERIALS AND METHODS The clinical data were collected from 288 eligible patients, and compared according to survival status and sites of infection acquisition. Drug resistance was recorded according to ESBL. In addition, cox regression analysis model was applied to evaluate the risk factors for 30-day mortality. CONCLUSIONS ESBL production can promote resistance to antibiotics in Escherichia coli. Antibiotic regimens, ICU admission, HE and MELD score can help identify the risk individuals who will benefit from the improved therapeutic regimens.
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Affiliation(s)
- Bo Tu
- Center for Infectious Disease, Beijing 302 Hospital, Beijing 100039, China
| | - Jingfeng Bi
- Center for Clinical Research Management, Beijing 302 Hospital, Beijing 100039, China
| | - Dan Wu
- Center for Infectious Disease, Beijing 302 Hospital, Beijing 100039, China
| | - Peng Zhao
- Center for Infectious Disease, Beijing 302 Hospital, Beijing 100039, China
| | - Lei Shi
- Center for Infectious Disease, Beijing 302 Hospital, Beijing 100039, China
| | - Yangxin Xie
- Center for Infectious Disease, Beijing 302 Hospital, Beijing 100039, China
| | - Xin Zhang
- Center for Infectious Disease, Beijing 302 Hospital, Beijing 100039, China
| | - Zhe Xu
- Center for Infectious Disease, Beijing 302 Hospital, Beijing 100039, China
| | - Suxia Liu
- Center for Liver Failure, Beijing 302 Hospital, Beijing 100039, China
| | - Xinhua Wang
- Center for Obstetrics and Gynecology, Beijing 302 Hospital, Beijing 100039, China
| | - Xiaoxi Li
- Center for Clinical Laboratory, Beijing 302 Hospital, Beijing 100039, China
| | - Fusheng Wang
- Center for Infectious Disease, Beijing 302 Hospital, Beijing 100039, China
| | - Enqiang Qin
- Center for Infectious Disease, Beijing 302 Hospital, Beijing 100039, China
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