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Li Y, Wu YT, Wu H. Management of hepatic encephalopathy following transjugular intrahepatic portosystemic shunts: Current strategies and future directions. World J Gastroenterol 2025; 31:103512. [PMID: 40309228 PMCID: PMC12038546 DOI: 10.3748/wjg.v31.i15.103512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 03/04/2025] [Accepted: 04/02/2025] [Indexed: 04/18/2025] Open
Abstract
Transjugular intrahepatic portosystemic shunts (TIPSs) are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis. However, hepatic encephalopathy (HE), which impairs neuropsychiatric function and motor control, remains the primary adverse effect of TIPS, limiting its utility. Prompt prevention and treatment of post-TIPS HE are critical, as they are strongly associated with readmission rates and poor quality of life. This review focuses on the main pathophysiological mechanisms underlying post-TIPS HE, explores advanced biomarkers and predictive tools, and discusses current management strategies and future directions to prevent or reverse HE following TIPS. These strategies include preoperative patient assessment, individualized shunt diameter optimization, spontaneous portosystemic shunt embolization during the TIPS procedure, postoperative preventive and therapeutic measures such as nutrition management, medical therapy, fecal microbiota transplantation, and stent reduction.
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Affiliation(s)
- Ying Li
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Tong Wu
- Chongqing Medical University-University of Leicester Joint Institute, Chongqing Medical University, Chongqing 400016, China
| | - Hao Wu
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Abdul Manan M. Progress in Probiotic Science: Prospects of Functional Probiotic-Based Foods and Beverages. INTERNATIONAL JOURNAL OF FOOD SCIENCE 2025; 2025:5567567. [PMID: 40259922 PMCID: PMC12011469 DOI: 10.1155/ijfo/5567567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 03/27/2025] [Indexed: 04/23/2025]
Abstract
This comprehensive review explores the evolving role of probiotic-based foods and beverages, highlighting their potential as functional and "future foods" that could significantly enhance nutrition, health, and overall well-being. These products are gaining prominence for their benefits in gut health, immune support, and holistic wellness. However, their future success depends on addressing critical safety concerns and navigating administrative complexities. Ensuring that these products "do more good than harm" involves rigorous evaluations of probiotic strains, particularly those sourced from the human gastrointestinal tract. Lactic acid bacteria (LABs) serve as versatile and effective functional starter cultures for the development of probiotic foods and beverages. The review emphasizes the role of LABs as functional starter cultures and the development of precision probiotics in advancing these products. Establishing standardized guidelines and transparent practices is essential, requiring collaboration among regulatory bodies, industry stakeholders, and the scientific community. The review underscores the importance of innovation in developing "friendly bacteria," "super probiotics," precision fermentation, and effective safety assessments. The prospects of functional probiotic-based foods and beverages rely on refining these elements and adapting to emerging scientific advancements. Ultimately, empowering consumers with accurate information, fostering innovation, and maintaining stringent safety standards will shape the future of these products as trusted and beneficial components of a health-conscious society. Probiotic-based foods and beverages, often infused with LABs, a "friendly bacteria," are emerging as "super probiotics" and "future foods" designed to "do more good than harm" for overall health.
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Affiliation(s)
- Musaalbakri Abdul Manan
- Food Science and Technology Research Centre, Malaysian Agricultural Research and Development Institute (MARDI), MARDI Headquarters, Persiaran MARDI-UPM, Serdang, Selangor, Malaysia
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Leitner U, Brits A, Xu D, Patil S, Sun J. Efficacy of probiotics on improvement of health outcomes in cirrhotic liver disease patients: A systematic review and meta-analysis of randomised controlled trials. Eur J Pharmacol 2024; 981:176874. [PMID: 39121983 DOI: 10.1016/j.ejphar.2024.176874] [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: 06/11/2024] [Revised: 07/23/2024] [Accepted: 08/05/2024] [Indexed: 08/12/2024]
Abstract
UNLABELLED Liver cirrhosis is a chronic condition of the liver and is the 14th most common cause of death around the world; yet it remains an incurable disease. Probiotics have gained significant popularity as a potential treatment option for liver cirrhosis. METHODS A systematic review and meta-analysis was conducted to assess the effects of probiotics on liver cirrhosis. PubMed, Scopus, Cochrane Central Register for Controlled Trials (CENTRAL) and ProQuest Dissertation and Thesis were searched from 2000 to January 2024 for studies that evaluated the effects of probiotics on a variety of outcomes of liver disease. RESULTS A total of 22 randomised controlled trial studies were included in the meta-analysis. Probiotics significantly decreased Gamma-glutamyl transferase (effect size: 0.307, p = 0.024, 95% CI [-0.572, -0.040]) and Aspartate aminotransferase (p = 0.013, 95% CI [-17.927, -2.128]). Significant reduction in serum ammonia levels (effect size = -1.093, p = 0.000, 95% CI [-1.764, -0.423]) and endotoxin levels (effect size = -0.961, p = 0.000, 95% CI [-1.537, -0.385]) were also found. SUMMARY Overall probiotics could be recommended as a potential adjunct therapy for patients with cirrhosis, as they appear to have some benefit in improving liver function, and are well tolerated with minimal adverse effects. More comprehensive research with larger sample sizes is recommended to understand more about the widespread effects of probiotic use.
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Affiliation(s)
- Unnah Leitner
- School of Medicine and Dentistry, Griffith University, Gold Coast, QLD 4215. Australia
| | - Anita Brits
- School of Medicine and Dentistry, Griffith University, Gold Coast, QLD 4215. Australia
| | - Dawei Xu
- Rural Health Research Institute, Charles Sturt University, New South Wales, NSW 2800, Australia; School of Medicine and Dentistry, Griffith University, Gold Coast, QLD 4215. Australia
| | - Sasha Patil
- School of Medicine and Dentistry, Griffith University, Gold Coast, QLD 4215. Australia
| | - Jing Sun
- Rural Health Research Institute, Charles Sturt University, New South Wales, NSW 2800, Australia; School of Medicine and Dentistry, Griffith University, Gold Coast, QLD 4215. Australia.
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Ashique S, Mishra N, Garg A, Kumar N, Khan Z, Mohanto S, Chellappan DK, Farid A, Taghizadeh-Hesary F. A Critical Review on the Role of Probiotics in Lung Cancer Biology and Prognosis. Arch Bronconeumol 2024; 60 Suppl 2:S46-S58. [PMID: 38755052 DOI: 10.1016/j.arbres.2024.04.030] [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: 02/20/2024] [Revised: 04/09/2024] [Accepted: 04/10/2024] [Indexed: 05/18/2024]
Abstract
Lung cancer remains the leading cause of cancer-related deaths worldwide. According to the American Cancer Society (ACS), it ranks as the second most prevalent type of cancer globally. Recent findings have highlighted bidirectional gut-lung interactions, known as the gut-lung axis, in the pathophysiology of lung cancer. Probiotics are live microorganisms that boost host immunity when consumed adequately. The immunoregulatory mechanisms of probiotics are thought to operate through the generation of various metabolites that impact both the gut and distant organs (e.g., the lungs) through blood. Several randomized controlled trials have highlighted the pivotal role of probiotics in gut health especially for the prevention and treatment of malignancies, with a specific emphasis on lung cancer. Current research indicates that probiotic supplementation positively affects patients, leading to a suppression in cancer symptoms and a shortened disease course. While clinical trials validate the therapeutic benefits of probiotics, their precise mechanism of action remains unclear. This narrative review aims to provide a comprehensive overview of the present landscape of probiotics in the management of lung cancer.
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Affiliation(s)
- Sumel Ashique
- Department of Pharmaceutical Sciences, Bengal College of Pharmaceutical Sciences & Research, Durgapur 713212, West Bengal, India.
| | - Neeraj Mishra
- Amity Institute of Pharmacy, Amity University Madhya Pradesh, Gwalior 474005, MP, India
| | - Ashish Garg
- Guru Ramdas Khalsa Institute of Science and Technology, Pharmacy, Jabalpur, MP 483001, India
| | - Nitish Kumar
- SRM Modinagar College of Pharmacy, SRM Institute of Science and Technology (Deemed to be University), Delhi-NCR Campus, Modinagar, Ghaziabad, Uttar Pradesh 201204, India
| | - Zuber Khan
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India
| | - Sourav Mohanto
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka 575018, India
| | - Dinesh Kumar Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
| | - Arshad Farid
- Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan
| | - Farzad Taghizadeh-Hesary
- ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Clinical Oncology, Iran University of Medical Sciences, Tehran, Iran.
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Yang X, Lei L, Shi W, Li X, Huang X, Lan L, Lin J, Liang Q, Li W, Yang J. Probiotics are beneficial for liver cirrhosis: a systematic review and meta-analysis of randomized control trials. Front Med (Lausanne) 2024; 11:1379333. [PMID: 38618195 PMCID: PMC11010643 DOI: 10.3389/fmed.2024.1379333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 03/19/2024] [Indexed: 04/16/2024] Open
Abstract
Introduction Gut dysbiosis may play a pivotal role in the pathogenesis of cirrhosis and the severity of complications. Numerous studies have investigated the probiotics as treatments for cirrhosis. However, there is still a lack of definitive evidence confirming the beneficial effects of probiotics on cirrhosis. Methods Databases including PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for randomized controlled trials that compared the effects of probiotic intervention and control treatments, including placebo, no treatment, and active control, on cirrhosis, published from inception to February 2024. Outcomes included hepatic encephalopathy (HE) reversal, safety and tolerability of probiotics, liver function, quality of life, and other cirrhotic-related outcomes. A meta-analysis was conducted to synthesize evidence. Results Thirty studies were included. The quantitative synthesis results showed that compared with the control group, probiotics significantly reverse minimal hepatic encephalopathy (MHE) (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.03 to 2.32) and improve HE (RR 1.94, 95% CI 1.24 to 3.06). Additionally, probiotics demonstrated higher safety and tolerability by causing a lower incidence of serious adverse events (RR 0.71, 95% CI 0.58 to 0.87). Probiotics could potentially improve liver function by reducing the Model for End-Stage Liver Disease (MELD) scores (standardized mean difference [SMD] -0.57, 95% CI -0.85 to -0.30), and displayed favorable changes in quality of life (SMD 0.51, 95% CI 0.27 to 0.75) and gut flora (SMD 1.67, 95% CI 1.28 to 2.06). Conclusion This systematic review and meta-analysis offers compelling evidence that probiotics are beneficial for cirrhosis by demonstrating reversal of HE, potential for liver function improvements, enhancements in quality of life, and regulation of gut dysbiosis. Furthermore, the apparent safety profile suggests that probiotics are a promising intervention for treating cirrhosis. Clinical trial registration number CRD42023478380.
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Affiliation(s)
- Xing Yang
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Langhuan Lei
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Wei Shi
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Xiaozhen Li
- Health Management Center, People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Xiaozhi Huang
- Health Management Center, People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Liuyan Lan
- Office of Hospital Quality and Safety Management Committee, People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Jiali Lin
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Qiuyu Liang
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Wei Li
- Health Management Center, People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
| | - Jianrong Yang
- Health Management Research Institute, People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences, Nanning, China
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Gala KS, Winrich E, Jha SK, Parthasarathy R, Vatsalya V. Alcohol Use Disorder and the Gut Microbiome. CURRENT ADDICTION REPORTS 2023; 11:105-112. [DOI: 10.1007/s40429-023-00527-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/30/2023] [Indexed: 01/04/2025]
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Ilie OD, Duta R, Nita IB, Dobrin I, Gurzu IL, Girleanu I, Huiban L, Muzica C, Ciobica A, Popescu R, Cianga P, Stanciu C, Cimpoesu D, Trifan A. A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2143. [PMID: 38138246 PMCID: PMC10744451 DOI: 10.3390/medicina59122143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/01/2023] [Accepted: 12/08/2023] [Indexed: 12/24/2023]
Abstract
Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.
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Affiliation(s)
- Ovidiu-Dumitru Ilie
- Gastroenterology Group, CENEMED Platform for Interdisciplinary Research, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
| | - Raluca Duta
- Gastroenterology Group, CENEMED Platform for Interdisciplinary Research, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
| | - Ilinca-Bianca Nita
- Department of Medicine III, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
| | - Irina Dobrin
- Department of Medicine III, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
- Institute of Psychiatry “Socola”, Bucium Street No. 36, 700282 Iasi, Romania
| | - Irina-Luciana Gurzu
- Department of Preventive Medicine and Interdisciplinarity, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” County Emergency Clinical Hospital, Independence Avenue No. 1, 700111 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” County Emergency Clinical Hospital, Independence Avenue No. 1, 700111 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” County Emergency Clinical Hospital, Independence Avenue No. 1, 700111 Iasi, Romania
| | - Alin Ciobica
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue No. 20A, 700505 Iasi, Romania
- Centre of Biomedical Research, Romanian Academy, Carol I Avenue No. 8, 700506 Iasi, Romania
- Academy of Romanian Scientists, Splaiul Independentei No. 54, Sector 5, 050094 Bucharest, Romania
- Preclinical Department, “Apollonia” University, Păcurari Street No. 11, 700511 Iasi, Romania
| | - Roxana Popescu
- Department of Medical Genetics, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
- Department of Medical Genetics, “Saint Mary” Emergency Children’s Hospital, Vasile Lupu Street No. 62, 700309 Iasi, Romania
| | - Petru Cianga
- Department of Immunology, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
| | - Carol Stanciu
- Centre of Biomedical Research, Romanian Academy, Carol I Avenue No. 8, 700506 Iasi, Romania
| | - Diana Cimpoesu
- Gastroenterology Group, CENEMED Platform for Interdisciplinary Research, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
- Department of Emergency Medicine, “St. Spiridon” County Emergency Clinical Hospital, Independence Avenue No. 1, 700111 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street No. 16, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” County Emergency Clinical Hospital, Independence Avenue No. 1, 700111 Iasi, Romania
- Centre of Biomedical Research, Romanian Academy, Carol I Avenue No. 8, 700506 Iasi, Romania
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Jiang H, Xu N, Zhang W, Wei H, Chen Y, Jiang Q, Zhou Y. Do gut microbiome-targeted therapies improve liver function in cirrhotic patients? A systematic review and meta-analysis. J Gastroenterol Hepatol 2023; 38:1900-1909. [PMID: 37582506 DOI: 10.1111/jgh.16329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 07/19/2023] [Accepted: 08/02/2023] [Indexed: 08/17/2023]
Abstract
BACKGROUND AND AIM Microbiome-targeted therapies (MTTs) are considered as promising interventions for cirrhosis, but the impact of gut microbiome modulation on liver function and disease severity has not been fully assessed. We comprehensively evaluated the efficacy of MTTs in patients with liver cirrhosis. METHODS Data from randomized controlled trials were collected through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrial.gov from inception to February 20, 2023. Clinical outcomes were pooled and expressed in terms of risk ratios or mean differences (MD). Additional subgroup and sensitivity analyses were performed to validate the robustness of findings. A trial sequential analysis was applied to calculate the required information size and evaluate the credibility of the meta-analysis results. RESULTS Twenty-one studies with a total of 1699 cirrhotic patients were included for meta-analysis. MTTs were associated with a significant reduction in aspartate aminotransferase (MD, -3.62; 95% CI, -6.59 to -0.65), the risk of hepatic encephalopathy (risk ratio = 0.56, 95% CI: 0.46 to 0.68), model for end-stage liver disease score (MD, -0.90; 95% CI, -1.17 to -0.11), ammonia (MD, -11.86; 95% CI, -16.39 to -7.33), and endotoxin (MD, -0.14; 95% CI, -0.23 to -0.04). The trial sequential analysis yielded reliable results of these outcomes. No effects were observed on the changes of other hepatic function indicators. CONCLUSION MTTs appeared to be associated with a slowed deterioration in liver cirrhosis, which could provide reference for clinicians in treatment of cirrhotic patients based on their conditions.
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Affiliation(s)
- Honglin Jiang
- School of Public Health, Fudan University, Shanghai, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China
- Fudan University Center for Tropical Disease Research, Shanghai, China
| | - Ning Xu
- School of Public Health, Fudan University, Shanghai, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China
- Fudan University Center for Tropical Disease Research, Shanghai, China
| | - Wei Zhang
- Department of Reference, Medical Library of Fudan University, Shanghai, China
| | - Hongjian Wei
- Department of Gastroenterology, The Third People's Hospital of Hunan, Yueyang, China
| | - Yue Chen
- School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Canada
| | - Qingwu Jiang
- School of Public Health, Fudan University, Shanghai, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China
- Fudan University Center for Tropical Disease Research, Shanghai, China
| | - Yibiao Zhou
- School of Public Health, Fudan University, Shanghai, China
- Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China
- Fudan University Center for Tropical Disease Research, Shanghai, China
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Xia Q, Lei Y, Wang J, Wang Q. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis. Open Life Sci 2023; 18:20220741. [PMID: 37872967 PMCID: PMC10590617 DOI: 10.1515/biol-2022-0741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 08/18/2023] [Accepted: 09/04/2023] [Indexed: 10/25/2023] Open
Abstract
The interaction between intestinal microecological dysregulation, altered inflammatory factors, and cirrhosis is unclear. The aim of this systematic review and meta-analysis was to synthesize the results of previous studies to assess the efficacy of probiotics in the treatment of cirrhosis and their effect on inflammatory factors, as well as to explore the relationship between gut microecological dysregulation and liver disease to gain a deeper understanding of this interaction. Up to December 2022, eligible studies were identified by searching the following databases: National Knowledge Infrastructure (CNKI), Wanfang Data, Web of Science, PubMed, Embase, Medline, and the Cochrane Library. Statistical analysis was performed using software RevMan Version 5.4. A total of 33 eligible randomized controlled trials were included in the study, and data on probiotic strains, duration of intervention, measures in the control group, and outcomes were extracted and evaluated. Compared to the control group, the experimental group had significant improvements in overall efficacy. The results of the meta-analysis revealed that probiotic use significantly decreased biochemical parameters for liver function, including aspartate transaminase, alanine aminotransferase, and total bilirubin. Similar result was obtained in interleukin-6, tumor necrosis factor-α, and endotoxin. However, probiotic intervention did not significantly affect interleukin-2 and interleukin-10. The current meta-analysis illustrates that probiotic supplementation reduces inflammatory markers and biochemical parameters for liver function in patients with cirrhosis, suggesting that probiotic management may be a novel treatment for cirrhosis. Furthermore, the interaction of the gut microbiota, associated metabolites, and inflammation factors with cirrhosis may provide a promising therapeutic target for the pharmacological and clinical treatment of cirrhosis.
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Affiliation(s)
- Qinglan Xia
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan430065, China
| | - Yumeng Lei
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan430065, China
| | - Jiadun Wang
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan430065, China
| | - Qiang Wang
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan430065, China
- Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan430056, China
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Gao J, Nie R, Chang H, Yang W, Ren Q. A meta-analysis of microbiome therapies for hepatic encephalopathy. Eur J Gastroenterol Hepatol 2023; 35:927-937. [PMID: 37505972 DOI: 10.1097/meg.0000000000002596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/30/2023]
Abstract
Microbiome therapies may be reported to be effective in hepatic encephalopathy (HE). We thus did a meta-analysis of randomized controlled trials to assess the effect of microbiome therapies for HE. We systematically searched PubMed, Web of Science, EMBASE, and Cochrane Library for randomized controlled trials that compared the different treatments for HE including probiotics, symbiotics, and fecal microbiota transplant (FMT). Meta-analysis was performed to calculate pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Twenty-one studies met our inclusion criteria (N = 1746 participants). Probiotics, synbiotics and FMT significantly reversed minimal HE (MHE) (OR: 0.41, 95% CI: 0.19-0.90, P = 0.03), reduced overt HE (OHE) development (OR, 0.41; 95% CI: 0.28-0.61 P < 0.00001)and the frequency of serious adverse events(SAEs) (OR:0.14, 95% CI: 0.04-0.47, P = 0.001), meanwhile decreased ammonia levels (WMD: -9.26, 95% CI: -16.92 to -1.61; P = 0.02), NCT level (MD = -4.41, 95% CI: -0.87 to -0.22, P = 0.04) and hospitalization rates (OR, 0.38; 95% CI: 0.19-0.79, P = 0.009) compared with placebo/no treatment. Finally, we conclude that microbiome therapies were more effective in improving MHE and preventing progression to OHE, reducing the frequency of SAEs, and decreasing ammonia levels, NCT level, and hospitalization rates when compared to placebo/no treatment.
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Affiliation(s)
- Jie Gao
- Lanzhou University
- Department of Gastroenterology, the First Hospital of Lanzhou University
| | - Rui Nie
- Lanzhou University
- Department of Gastroenterology, the First Hospital of Lanzhou University
| | - Hong Chang
- Lanzhou University
- Department of Gastroenterology, the First Hospital of Lanzhou University
| | - Wei Yang
- Lanzhou University
- Department of Gastroenterology, the First Hospital of Lanzhou University
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Qian Ren
- Lanzhou University
- Department of Gastroenterology, the First Hospital of Lanzhou University
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
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Wu Z, Zhou H, Liu D, Deng F. Alterations in the gut microbiota and the efficacy of adjuvant probiotic therapy in liver cirrhosis. Front Cell Infect Microbiol 2023; 13:1218552. [PMID: 37483387 PMCID: PMC10361729 DOI: 10.3389/fcimb.2023.1218552] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 06/15/2023] [Indexed: 07/25/2023] Open
Abstract
BACKGROUND Liver cirrhosis is the end stage of various chronic liver diseases (CLDs). The gut microbiota can impact the liver environment and trigger chronic liver inflammation through the gut-liver axis. Alteration of the gut microbiota has become an effective strategy in the biological treatment of cirrhosis. METHODS Twenty-eight patients with liver cirrhosis and 16 healthy individuals were included, and fresh stool samples were collected. We analyzed changes in the gut microbiota between groups by 16S rRNA sequencing and evaluated the association between microbiota alterations and hepatic function. Additionally, 102 cirrhotic patients were retrospectively enrolled and divided into a probiotic group (n=44) and a nonprobiotic group (n=58) in addition to standard treatment for cirrhosis. Patients were monitored for hematological parameters and hepatic function during the six-month follow-up. RESULTS The gut microbiota profile of patients with cirrhosis was greatly different from that of healthy individuals, presenting with significantly reduced α diversity and decreased abundance of representative SCFA-producing bacteria including Firmicutes, Coprococcus and Clostridium IV. The pathogenic bacteria Gammaproteobacteria, Veillonella, and Bacilli were greatly enriched in cirrhotic patients. Additionally, patients with decompensated cirrhosis (DCPC) had a significantly reduced abundance of Oscillibacter compared to compensated cirrhosis (CPC), which is also a SCFA-producing bacteria, and the lower Firmicutes to Bacteroidetes ratio and enhanced MDR values were also shown in DCPC patients compared to CPC patients. In addition, the abundance of Firmicutes was negatively related to hepatic function in cirrhotic patients, including the levels of ALT, AST, and DBIL. From the retrospective study, we found that biochemical improvements in alanine transaminase (ALT) and total bilirubin (TBIL) were obtained in DCPC patients who received oral probiotic therapy compared with the nonprobiotic group. CONCLUSION Severe microbial dysbiosis existed in patients with liver cirrhosis, especially patients who reached the decompensatory stage. SCFA-producing bacteria were significantly reduced in cirrhosis. Altered gut microbiota cause changes in functional modules, which may contribute to cirrhosis progression and are associated with clinical prognosis. Adjuvant probiotic supplementation to enhance SCFA-producing bacteria can be a prospective therapy for patients with cirrhosis.
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Affiliation(s)
- Zengrong Wu
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
| | - Hejun Zhou
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
| | - Deliang Liu
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
| | - Feihong Deng
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
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12
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Huang L, Yu Q, Peng H, Zhen Z. Alterations of gut microbiome and effects of probiotic therapy in patients with liver cirrhosis: A systematic review and meta-analysis. Medicine (Baltimore) 2022; 101:e32335. [PMID: 36595801 PMCID: PMC9794299 DOI: 10.1097/md.0000000000032335] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Alterations in the gut microbiome usually occur in liver cirrhosis. Gut microbiome dysregulation damages the liver and accelerates the development of liver fibrosis. Probiotic treatment has gradually become a major method for improving the prognosis of liver cirrhosis and reducing its complications. However, alterations in the gut microbiome have revealed different results, and the therapeutic effects of various probiotics are inconsistent. METHODS We searched the PubMed, Medline, EMBASE, ScienceDirect, and Cochrane databases up to August 2022 and conducted a systematic review and meta-analysis of 17 relevant studies. RESULTS The counts of Enterobacter (standardized mean difference [SMD] -1.79, 95% confidence interval [CI]: -3.08 to -0.49) and Enterococcus (SMD -1.41, 95% CI: -2.26 to -0.55) increased significantly in patients with cirrhosis, while the counts of Lactobacillus (SMD 0.63, 95% CI: 0.12-1.15) and Bifidobacterium (SMD 0.44, 95% CI: 0.12-0.77) decreased significantly. Blood ammonia (weighted mean difference [WMD] 14.61, 95% CI: 7.84-21.37) and the incidence of hepatic encephalopathy (WMD 0.40, 95% CI: 0.27-0.61) were significantly decreased in the probiotic group. As for mortality (MD 0.75, 95% CI: 0.48-1.16) and the incidence of spontaneous bacterial peritonitis (WMD -0.02, 95% CI: -0.07 to 0.03), no significant differences were found between the probiotic and placebo groups. CONCLUSION In summary, the gut microbiome in cirrhosis manifests as decreased counts of Lactobacillus and Bifidobacterium and increased counts of Enterobacter and Enterococcus. Targeted supplementation of probiotics in cirrhosis, including Lactobacillus combined with Bifidobacterium or Bifidobacterium alone, can reduce blood ammonia and the incidence of hepatic encephalopathy. The effect is similar to that of lactulose, but it has no obvious effect on mortality and spontaneous bacterial peritonitis.
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Affiliation(s)
- Long Huang
- Department of No. 1 Surgery, The First Hospital Affiliated to Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, China
- * Correspondence: Long Huang, The First Hospital Affiliated to Anhui University of Traditional Chinese Medicine, No. 117 Meishan Road, Hefei, Anhui Province 230031, China (e-mail: )
| | - Qingsheng Yu
- Department of No. 1 Surgery, The First Hospital Affiliated to Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, China
| | - Hui Peng
- Department of No. 1 Surgery, The First Hospital Affiliated to Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, China
| | - Zhou Zhen
- Department of Surgery, The Second Hospital Affiliated to Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, China
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Jeong JJ, Park HJ, Cha MG, Park E, Won SM, Ganesan R, Gupta H, Gebru YA, Sharma SP, Lee SB, Kwon GH, Jeong MK, Min BH, Hyun JY, Eom JA, Yoon SJ, Choi MR, Kim DJ, Suk KT. The Lactobacillus as a Probiotic: Focusing on Liver Diseases. Microorganisms 2022; 10:288. [PMID: 35208742 PMCID: PMC8879051 DOI: 10.3390/microorganisms10020288] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 01/18/2022] [Accepted: 01/23/2022] [Indexed: 12/12/2022] Open
Abstract
Over the past decade, scientific evidence for the properties, functions, and beneficial effects of probiotics for humans has continued to accumulate. Interest in the use of probiotics for humans has increased tremendously. Among various microorganisms, probiotics using bacteria have been widely studied and commercialized, and, among them, Lactobacillus is representative. This genus contains about 300 species of bacteria (recently differentiated into 23 genera) and countless strains have been reported. They improved a wide range of diseases including liver disease, gastrointestinal diseases, respiratory diseases, and autoimmune diseases. Here, we intend to discuss in depth the genus Lactobacillus as a representative probiotic for chronic liver diseases.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Ki Tae Suk
- Institute for Liver and Digestive Diseases, Hallym University College of Medicine, Chuncheon 24252, Korea; (J.-J.J.); (H.J.P.); (M.G.C.); (E.P.); (S.-M.W.); (R.G.); (H.G.); (Y.A.G.); (S.P.S.); (S.B.L.); (G.H.K.); (M.K.J.); (B.H.M.); (J.Y.H.); (J.A.E.); (S.J.Y.); (M.R.C.); (D.J.K.)
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14
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Influence of Probiotics Administration Before Liver Resection in Patients with Liver Disease: A Randomized Controlled Trial. World J Surg 2021; 46:656-665. [PMID: 34837121 DOI: 10.1007/s00268-021-06388-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/24/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND By inhibiting the growth of pathogenic bacteria and modulating the local intestinal immune system, probiotics may reduce bacterial translocation and systemic endotoxaemia, factors partially responsible for post-operative complications following liver resection for hepatocellular carcinoma in patients with cirrhosis. METHODS Patients with resectable hepatocellular carcinoma developed in the setting of chronic liver disease were prospectively divided into two equal-sized groups: one receiving probiotic treatment 14 days prior to surgery and the other receiving placebo. The primary endpoint was the level of circulating endotoxins after hepatectomy. Secondary endpoints were systemic inflammation (inflammatory cytokine levels), post-operative liver function and overall post-operative complication rate. RESULTS From May 2013 to December 2018, 64 patients were randomized, and 54 patients were included in the analysis, 27 in each arm. No significant change in endotoxin levels was observed over time in either group (P = 0.299). No difference between the groups in terms of post-operative liver function and overall complication rates was observed. The only differences observed were significant increases in the levels of TNFalpha (P = 0.019) and interleukin 1-b (P = 0.028) in the probiotic group in the post-operative period. CONCLUSION Contrary to the modest data reported in the literature, the administration of probiotics before minor liver resection for hepatocellular carcinoma developed in the setting of compensated chronic liver disease does not seem to have an impact on circulating endotoxin levels or post-operative complication rates. TRIAL REGISTRATION Trial registration: NCT02021253.
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Micioni Di Bonaventura MV, Coman MM, Tomassoni D, Micioni Di Bonaventura E, Botticelli L, Gabrielli MG, Rossolini GM, Di Pilato V, Cecchini C, Amedei A, Silvi S, Verdenelli MC, Cifani C. Supplementation with Lactiplantibacillus plantarum IMC 510 Modifies Microbiota Composition and Prevents Body Weight Gain Induced by Cafeteria Diet in Rats. Int J Mol Sci 2021; 22:11171. [PMID: 34681831 PMCID: PMC8540549 DOI: 10.3390/ijms222011171] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/11/2021] [Accepted: 10/12/2021] [Indexed: 12/19/2022] Open
Abstract
Changes in functionality and composition of gut microbiota (GM) have been associated and may contribute to the development and maintenance of obesity and related diseases. The aim of our study was to investigate for the first time the impact of Lactiplantibacillus (L.) plantarum IMC 510 in a rat model of diet-induced obesity, specifically in the cafeteria (CAF) diet. This diet provides a strong motivation to voluntary overeat, due to the palatability and variety of selected energy-dense foods. The oral administration for 84 days of this probiotic strain, added to the CAF diet, decreased food intake and body weight gain. Accordingly, it ameliorated body mass index, liver and white adipose tissue weight, hepatic lipid accumulation, adipocyte size, serum parameters, including glycemia and low-density lipoprotein levels, in CAF fed rats, potentially through leptin control. In this scenario, L. plantarum IMC 510 showed also beneficial effects on GM, limiting the microbial imbalance established by long exposure to CAF diet and preserving the proportion of different bacterial taxa. Further research is necessary to better elucidate the relationship between GM and overweight and then the mechanism of action by which L. plantarum IMC 510 modifies weight. However, these promising results prompt a clear advantage of probiotic supplementation and identify a new potential probiotic as a novel and safe therapeutic approach in obesity prevention and management.
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Affiliation(s)
| | - Maria Magdalena Coman
- Synbiotec S.r.l., Spin-off of UNICAM, Via Gentile III Da Varano, 62032 Camerino, Italy; (M.M.C.); (C.C.); (M.C.V.)
| | - Daniele Tomassoni
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy; (D.T.); (M.G.G.)
| | - Emanuela Micioni Di Bonaventura
- Pharmacology Unit, School of Pharmacy, University of Camerino, 62032 Camerino, Italy; (M.V.M.D.B.); (E.M.D.B.); (L.B.); (C.C.)
| | - Luca Botticelli
- Pharmacology Unit, School of Pharmacy, University of Camerino, 62032 Camerino, Italy; (M.V.M.D.B.); (E.M.D.B.); (L.B.); (C.C.)
| | - Maria Gabriella Gabrielli
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy; (D.T.); (M.G.G.)
| | - Gian Maria Rossolini
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy; (G.M.R.); (A.A.)
- Microbiology and Virology Unit, Florence Careggi University Hospital, 50134 Florence, Italy
| | - Vincenzo Di Pilato
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, 16132 Genova, Italy;
| | - Cinzia Cecchini
- Synbiotec S.r.l., Spin-off of UNICAM, Via Gentile III Da Varano, 62032 Camerino, Italy; (M.M.C.); (C.C.); (M.C.V.)
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy; (G.M.R.); (A.A.)
| | - Stefania Silvi
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy; (D.T.); (M.G.G.)
| | - Maria Cristina Verdenelli
- Synbiotec S.r.l., Spin-off of UNICAM, Via Gentile III Da Varano, 62032 Camerino, Italy; (M.M.C.); (C.C.); (M.C.V.)
| | - Carlo Cifani
- Pharmacology Unit, School of Pharmacy, University of Camerino, 62032 Camerino, Italy; (M.V.M.D.B.); (E.M.D.B.); (L.B.); (C.C.)
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16
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Dell’Anno M, Callegari ML, Reggi S, Caprarulo V, Giromini C, Spalletta A, Coranelli S, Sgoifo Rossi CA, Rossi L. Lactobacillus plantarum and Lactobacillus reuteri as Functional Feed Additives to Prevent Diarrhoea in Weaned Piglets. Animals (Basel) 2021; 11:ani11061766. [PMID: 34204784 PMCID: PMC8231520 DOI: 10.3390/ani11061766] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 05/28/2021] [Accepted: 06/08/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Antimicrobial resistance is an increasing global concern. Effective alternatives that could replace and reduce antimicrobial treatments in farming have therefore become crucial for animal, human and environmental health. In swine farming, weaning is a stressful phase where piglets can develop multifactorial enteric disorders that require antibiotic treatments. Functional nutrition could thus represent a valuable alternative to reduce and tackle antibiotic resistance. This study assesses the effects of Lactobacillus plantarum and Lactobacillus reuteri on in-feed supplementation in weaned piglets. After weaning, piglets were allotted to four experimental groups fed a basal diet (CTRL) and a basal diet supplemented with 2 × 108 CFU/g of L. plantarum (PLA), L. reuteri and a combination of the two strains (P+R) for 28 days. Zootechnical performance and diarrhoea occurrence were recorded. Microbiological and serum metabolism analyses of faeces and blood samples were performed. Supplemented groups with lactobacilli showed a lower occurrence of diarrhoea and improved faecal consistency compared to the control. The PLA group registered the lowest diarrhoea frequency during the 28-day experimental period. The results suggest that dietary administration of L. plantarum and L. reuteri could prevent the occurrence of diarrhoea in weaned piglets. Abstract The effects of Lactobacillus plantarum and Lactobacillus reuteri and their combination were assessed in weaned piglets. Three hundred and fifty weaned piglets (Landrace × Large White), balanced in terms of weight and sex, were randomly allotted to four experimental groups (25 pens, 14 piglets/pen). Piglets were fed a basal control diet (CTRL, six pens) and a treatment diet supplemented with 2 × 108 CFU/g of L. plantarum (PLA, 6 pens), 2 × 108 CFU/g L. reuteri (REU, six pens) and the combination of both bacterial strains (1 × 108 CFU/g of L. plantarum combined with 1 × 108 CFU/g of L. reuteri, P+R, 7 pens) for 28 days. Body weight and feed intake were recorded weekly. Diarrhoea occurrence was assessed weekly by the faecal score (0–3; considering diarrhoea ≥ 2). At 0 and 28 days, faecal samples were obtained from four piglets per pen for microbiological analyses and serum samples were collected from two piglets per pen for serum metabolic profiling. Treatments significantly reduced diarrhoea occurrence and decreased the average faecal score (0.94 ± 0.08 CTRL, 0.31 ± 0.08 PLA, 0.45 ± 0.08 REU, 0.27 ± 0.08 P+R; p < 0.05). The PLA group registered the lowest number of diarrhoea cases compared to other groups (20 cases CTRL, 5 cases PLA, 8 cases REU, 10 cases P+R; p < 0.01). After 28 days, the globulin serum level increased in PLA compared to the other groups (24.91 ± 1.09 g/L CTRL, 28.89 ± 1.03 g/L PLA, 25.91 ± 1.03 g/L REU, 25.31 ± 1.03 g/L P+R; p < 0.05). L. plantarum and L. reuteri could thus be considered as interesting functional additives to prevent diarrhoea occurrence in weaned piglets.
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Affiliation(s)
- Matteo Dell’Anno
- Department of Health, Animal Science and Food Safety “Carlo Cantoni” (VESPA), Università degli Studi di Milano, 26900 Lodi, Italy; (S.R.); (C.G.); (C.A.S.R.); (L.R.)
- Correspondence:
| | - Maria Luisa Callegari
- Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, 29122 Piacenza, Italy;
| | - Serena Reggi
- Department of Health, Animal Science and Food Safety “Carlo Cantoni” (VESPA), Università degli Studi di Milano, 26900 Lodi, Italy; (S.R.); (C.G.); (C.A.S.R.); (L.R.)
| | - Valentina Caprarulo
- Department of Molecular and Translational Medicine (DMMT), Università degli Studi di Brescia, 25123 Brescia, Italy;
| | - Carlotta Giromini
- Department of Health, Animal Science and Food Safety “Carlo Cantoni” (VESPA), Università degli Studi di Milano, 26900 Lodi, Italy; (S.R.); (C.G.); (C.A.S.R.); (L.R.)
| | | | | | - Carlo Angelo Sgoifo Rossi
- Department of Health, Animal Science and Food Safety “Carlo Cantoni” (VESPA), Università degli Studi di Milano, 26900 Lodi, Italy; (S.R.); (C.G.); (C.A.S.R.); (L.R.)
| | - Luciana Rossi
- Department of Health, Animal Science and Food Safety “Carlo Cantoni” (VESPA), Università degli Studi di Milano, 26900 Lodi, Italy; (S.R.); (C.G.); (C.A.S.R.); (L.R.)
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Rackayová V, Flatt E, Braissant O, Grosse J, Capobianco D, Mastromarino P, McMillin M, DeMorrow S, McLin VA, Cudalbu C. Probiotics improve the neurometabolic profile of rats with chronic cholestatic liver disease. Sci Rep 2021; 11:2269. [PMID: 33500487 PMCID: PMC7838316 DOI: 10.1038/s41598-021-81871-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
Chronic liver disease leads to neuropsychiatric complications called hepatic encephalopathy (HE). Current treatments have some limitations in their efficacy and tolerability, emphasizing the need for alternative therapies. Modulation of gut bacterial flora using probiotics is emerging as a therapeutic alternative. However, knowledge about how probiotics influence brain metabolite changes during HE is missing. In the present study, we combined the advantages of ultra-high field in vivo 1H MRS with behavioural tests to analyse whether a long-term treatment with a multistrain probiotic mixture (VIVOMIXX) in a rat model of type C HE had a positive effect on behaviour and neurometabolic changes. We showed that the prophylactic administration of this probiotic formulation led to an increase in gut Bifidobacteria and attenuated changes in locomotor activity and neurometabolic profile in a rat model of type C HE. Both the performance in behavioural tests and the neurometabolic profile of BDL + probiotic rats were improved compared to the BDL group at week 8 post-BDL. They displayed a significantly lesser increase in brain Gln, a milder decrease in brain mIns and a smaller decrease in neurotransmitter Glu than untreated animals. The clinical implications of these findings are potentially far-reaching given that probiotics are generally safe and well-tolerated by patients.
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Affiliation(s)
- Veronika Rackayová
- Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
- Center for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Vaud, Switzerland
| | - Emmanuelle Flatt
- Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Olivier Braissant
- Service of Clinical Chemistry, University of Lausanne and University Hospital of Lausanne, Lausanne, Switzerland
| | - Jocelyn Grosse
- Laboratory of Behavioral Genetics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Daniela Capobianco
- Department of Public Health and Infectious Diseases, Section of Microbiology, Sapienza University of Rome, Rome, Italy
| | - Paola Mastromarino
- Department of Public Health and Infectious Diseases, Section of Microbiology, Sapienza University of Rome, Rome, Italy
| | - Matthew McMillin
- Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, TX, USA
- Central Texas Veterans Health Care System, Temple, TX, USA
| | - Sharon DeMorrow
- Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, TX, USA
- Central Texas Veterans Health Care System, Temple, TX, USA
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
| | - Valérie A McLin
- Swiss Pediatric Liver Center, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva and University Hospitals Geneva, Geneva, Switzerland
| | - Cristina Cudalbu
- Center for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Vaud, Switzerland.
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Nishikawa H, Enomoto H, Nishiguchi S, Iijima H. Liver Cirrhosis and Sarcopenia from the Viewpoint of Dysbiosis. Int J Mol Sci 2020; 21:5254. [PMID: 32722100 PMCID: PMC7432211 DOI: 10.3390/ijms21155254] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/15/2020] [Accepted: 07/19/2020] [Indexed: 02/06/2023] Open
Abstract
Sarcopenia in patients with liver cirrhosis (LC) has been attracting much attention these days because of the close linkage to adverse outcomes. LC can be related to secondary sarcopenia due to protein metabolic disorders and energy metabolic disorders. LC is associated with profound alterations in gut microbiota and injuries at the different levels of defensive mechanisms of the intestinal barrier. Dysbiosis refers to a state in which the diversity of gut microbiota is decreased by decreasing the bacterial species and the number of bacteria that compose the gut microbiota. The severe disturbance of intestinal barrier in LC can result in dysbiosis, several bacterial infections, LC-related complications, and sarcopenia. Here in this review, we will summarize the current knowledge of the relationship between sarcopenia and dysbiosis in patients with LC.
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Affiliation(s)
- Hiroki Nishikawa
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya 6638136, Japan; (H.E.); (H.I.)
- Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya 6638136, Japan
| | - Hirayuki Enomoto
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya 6638136, Japan; (H.E.); (H.I.)
| | | | - Hiroko Iijima
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya 6638136, Japan; (H.E.); (H.I.)
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19
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Yokoyama K, Tsuchiya N, Yamauchi R, Miyayama T, Uchida Y, Shibata K, Fukuda H, Umeda K, Takata K, Tanaka T, Inomata S, Morihara D, Takeyama Y, Shakado S, Sakisaka S, Hirai F. Exploratory Research on the Relationship between Human Gut Microbiota and Portal Hypertension. Intern Med 2020; 59:2089-2094. [PMID: 32879200 PMCID: PMC7516306 DOI: 10.2169/internalmedicine.4628-20] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Objective The relationship between gut microbiota and portal hypertension remains unclear. We investigated the characteristics of the gut microbiota in portal hypertension patients with esophago-gastric varices and liver cirrhosis. Methods Thirty-six patients (12 patients with portal hypertension, 12 healthy controls, and 12 non-cirrhosis patients) were enrolled in this university hospital study. Intestinal bacteria and statistical analyses were performed up to the genus level using the terminal restriction fragment length polymorphism method targeting 16S ribosomal RNA genes, with diversified regions characterizing each bacterium. Results Levels of Lactobacillales were significantly higher (p=0.045) and those of Clostridium cluster IV significantly lower (p=0.014) in patients with portal hypertension than in other patients. This Clostridium cluster contains many butanoic acid-producing strains, including Ruminococcace and Faecalibacterium prausnitzii. Clostridium cluster IX levels were also significantly lower (p=0.045) in portal hypertension patients than in other patients. There are many strains of Clostridium that produce propionic acid, and the effects on the host and the function of these bacterial species in the human intestine remain unknown. Regarding the Bifidobacterium genus, which is supposed to decrease as a result of cirrhosis, no significant decrease was observed in this study. Conclusion In the present study, we provided information on the characteristics of the gut microbiota of portal hypertension patients with esophago-gastric varices due to liver cirrhosis. In the future, we aim to develop probiotic treatments following further analyses that include the species level, such as the intestinal flora analysis method and next-generation sequencers.
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Affiliation(s)
- Keiji Yokoyama
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Naoaki Tsuchiya
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Ryo Yamauchi
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Takashi Miyayama
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Yotaro Uchida
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Kumiko Shibata
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Hiromi Fukuda
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Kaoru Umeda
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Kazuhide Takata
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Takashi Tanaka
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Shinjiro Inomata
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Daisuke Morihara
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Yasuaki Takeyama
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Satoshi Shakado
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Shotaro Sakisaka
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
| | - Fumihito Hirai
- Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Japan
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Abstract
Microbiome dysbiosis is strongly associated with alcoholic liver disease (ALD). Recent studies on comprehensive analyses of microbiome compositional and functional changes have begun to uncover the mechanistic relation between microbiome and the pathogenesis of ALD. Importantly, targeting the microbiome has become a potential strategy for the prevention and treatment of ALD. In this review, we summarize the clinical evidence of microbiome dysbiosis in ALD patients, and experimental advances in microbiome and metabolomic functional changes in animals with different species and genetic backgrounds in ALD. We also summarize the studies in humanized intestinal microbiome and fecal microbiota transplantation in mice. We introduce new developments in the studies on the role of the circulating bacterial microbiome, oral bacterial microbiome and fungal microbiome in the development of ALD. We highlight the potential mechanisms by which microbiome dysbiosis contributes to ALD, including short chain fatty acid changes, bile acid metabolism, intestinal barrier function, release of bacterial and fungal products, and inflammation. In addition, we summarize the recent developments targeting the microbiome in prevention and treatment of ALD, including dietary nutrient interference, herbal medicine, antibiotics, anti-fungal agents, probiotics, engineered bacterial therapy, fecal transplantation and oral hygiene. Although recent preclinical studies have advanced our understanding of the microbiome and ALD, clinical studies, especially prospective studies with large samples, are needed to better understand the cause-effect of microbiome dysbiosis in ALD. Identifying new precision-based strategies targeting the microbiome are expected to be developed as more effective therapies in ALD.
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Fang TJ, Guo JT, Lin MK, Lee MS, Chen YL, Lin WH. Protective effects of Lactobacillus plantarum against chronic alcohol-induced liver injury in the murine model. Appl Microbiol Biotechnol 2019; 103:8597-8608. [PMID: 31515596 DOI: 10.1007/s00253-019-10122-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 08/26/2019] [Accepted: 09/04/2019] [Indexed: 02/07/2023]
Abstract
Long-term alcohol consumption causes liver injuries such as alcoholic hepatitis, fatty liver, and endotoxemia. Some probiotics were demonstrated to exert beneficial effects in the gastrointestinal tract. The present study was aimed to evaluate the protective effects of Lactobacillus plantarum CMU995 against alcohol-induced liver injury. The mice were orally administered L. plantarum CMU995 for 1 week, followed by the administration of alcohol and different tested substances daily for 6 weeks. The liver injury was examined by measuring the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), anti-oxidative enzyme, endotoxin, inflammatory cytokines, and lipid accumulation in the liver or serum among different groups. L. plantarum CMU995 exhibited beneficial effects on alcohol-induced liver injury via reduction in the serum concentration of AST, ALT, cholesterol, triglycerides, endotoxin, TNF-α, IL-1β, and oxidative stress. Furthermore, we also found that the levels of glutathione (GSH), superoxide dismutase (SOD), and intestinal tight junction protein zonula occludens-1 (ZO-1) were considerably higher in L. plantarum CMU995-fed groups when compared with placebo group. Meanwhile, the protective effects were demonstrated biological gradients as controversial dose-dependent. We speculate that L. plantarum CMU995 inhibited the migration of alcohol-derived endotoxin into the blood and liver, thereby improving the intestinal barrier. The present evidence may provide a novel microbiota-based strategy to prevent the alcohol-induced liver injury.
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Affiliation(s)
- Tony J Fang
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, Republic of China
| | - Jiun-Ting Guo
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, Republic of China.,Department of Pharmacy, China Medical University, Taichung, Taiwan, Republic of China
| | - Ming-Kuem Lin
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung, Taiwan, Republic of China
| | - Meng-Shiou Lee
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung, Taiwan, Republic of China
| | - Yen-Lien Chen
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, Republic of China
| | - Wen-Hsin Lin
- Department of Pharmacy, China Medical University, Taichung, Taiwan, Republic of China. .,College of Pharmacy, China Medical University, No. 91, Hsueh Shih Road, Taichung, 404, Taiwan, Republic of China.
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Cho MS, Kim SY, Suk KT, Kim BY. Modulation of gut microbiome in nonalcoholic fatty liver disease: pro-, pre-, syn-, and antibiotics. J Microbiol 2018; 56:855-867. [PMID: 30377993 DOI: 10.1007/s12275-018-8346-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 08/08/2018] [Accepted: 08/21/2018] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common types of liver diseases worldwide and its incidence continues to increase. NAFLD occurs when the body can no longer effectively store excess energy in the adipose tissue. Despite the increasing prevalence of NAFLD, making lifestyle changes, including increased exercise, is often an elusive goal for patients with NAFLD. The liver directly connects to the gut-gastrointestinal milieu via the portal vein, which are all part of the gut-liver axis. Therefore, the gut-microbiome and microbial products have been actively studied as likely key factors in NAFLD pathophysiology. Hence, dysbiosis of the gut microbiome and therapeutic manipulation of the gut-liver axis are being investigated. Novel therapeutic approaches for modulating gut microbiota through the administration of probiotics, prebiotics, synbiotics, and antibiotics have been proposed with numerous promising initial reports on the effectiveness and clinical applications of these approaches. This review delves into the current evidence on novel therapies that modulate gut microbiota and discusses ongoing clinical trials targeting the gut-liver axis for the management and prevention of NAFLD.
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Affiliation(s)
| | - Sang Yeol Kim
- Division of Gastroenterology and Hepatology, College of Medicine, Hallym University, Chuncheon, 24253, Republic of Korea
| | - Ki Tae Suk
- Division of Gastroenterology and Hepatology, College of Medicine, Hallym University, Chuncheon, 24253, Republic of Korea.
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Xia X, Chen J, Xia J, Wang B, Liu H, Yang L, Wang Y, Ling Z. Role of probiotics in the treatment of minimal hepatic encephalopathy in patients with HBV-induced liver cirrhosis. J Int Med Res 2018; 46:3596-3604. [PMID: 29806520 PMCID: PMC6135989 DOI: 10.1177/0300060518776064] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 04/19/2018] [Indexed: 12/20/2022] Open
Abstract
Objective This study was performed to investigate the role of probiotics ( Clostridium butyricum combined with Bifidobacterium infantis) in the treatment of minimal hepatic encephalopathy (MHE) in patients with hepatitis B virus (HBV)-induced liver cirrhosis. Methods Sixty-seven consecutive patients with HBV-induced cirrhosis without overt hepatic encephalopathy were screened using the number connection test and digit symbol test. The patients were randomized to receive probiotics (n = 30) or no probiotics (n = 37) for 3 months. At the end of the trial, changes in cognition, intestinal microbiota, venous ammonia, and intestinal mucosal barriers were analyzed using recommended systems biology techniques. Results The patients' cognition was significantly improved after probiotic treatment. The predominant bacteria ( Clostridium cluster I and Bifidobacterium) were significantly enriched in the probiotics-treated group, while Enterococcus and Enterobacteriaceae were significantly decreased. Probiotic treatment was also associated with an obvious reduction in venous ammonia. Additionally, the parameters of the intestinal mucosal barrier were obviously improved after probiotic treatment, which might have contributed to the improved cognition and the decreased ammonia levels. Conclusion Treatment with probiotics containing C. butyricum and B. infantis represents a new adjuvant therapy for the management of MHE in patients with HBV-induced cirrhosis.
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Affiliation(s)
- Xiaoxue Xia
- Department of Infectious Diseases, Changxing People’s Hospital,
Huzhou, Zhejiang, China
| | - Jiang Chen
- Department of Infectious Diseases, Changxing People’s Hospital,
Huzhou, Zhejiang, China
| | - Jiayun Xia
- Department of Infectious Diseases, Changxing People’s Hospital,
Huzhou, Zhejiang, China
| | - Bin Wang
- Department of Infectious Diseases, Changxing People’s Hospital,
Huzhou, Zhejiang, China
| | - Hua Liu
- Department of Infectious Diseases, Changxing People’s Hospital,
Huzhou, Zhejiang, China
| | - Ling Yang
- Department of Infectious Diseases, Changxing People’s Hospital,
Huzhou, Zhejiang, China
| | - Ying Wang
- Department of Infectious Diseases, Changxing People’s Hospital,
Huzhou, Zhejiang, China
| | - Zongxin Ling
- Collaborative Innovation Center for Diagnosis and Treatment of
Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of
Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang
University, Hangzhou, Zhejiang, China
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Cao Q, Yu CB, Yang SG, Cao HC, Chen P, Deng M, Li LJ. Effect of probiotic treatment on cirrhotic patients with minimal hepatic encephalopathy: A meta-analysis. Hepatobiliary Pancreat Dis Int 2018; 17:9-16. [PMID: 29428113 DOI: 10.1016/j.hbpd.2018.01.005] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Accepted: 11/07/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Minimal hepatic encephalopathy (MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to verify the role of probiotics in the treatment of cirrhotic patients with MHE. DATA SOURCES Seven electronic databases were searched for relevant randomized controlled trials (RCTs) published until July 2015. The effects of probiotics on serum ammonia, endotoxin, and MHE were evaluated. RESULTS A total of 14 RCTs (combined n = 1132) were included in the meta-analysis. When probiotics were compared to placebo or no treatment, probiotics were more likely to reduce values in the number connection test (NCT; week 4: MD = -30.25, 95% CI: -49.85 to -10.66), improve MHE (week 4: OR = 0.18, 95% CI: 0.07 to 0.47; week 12: OR = 0.15, 95% CI: 0.07 to 0.32), and prevent overt HE progression (week 4: OR = 0.22, 95% CI: 0.07 to 0.67) in patients with liver cirrhosis. When probiotics was compared to lactulose, probiotics tended to reduce serum ammonia levels (week 4: MD = -0.33 µmol/L, 95% CI: -5.39 to 4.74; week 8: MD = 6.22 µmol/L, 95% CI: -24.04 to 36.48), decrease NCT (week 8: MD = 3.93, 95% CI: -0.72 to 8.58), improve MHE (week 4: OR = 0.93, 95% CI: 0.45 to 1.91; week 12: OR = 0.73, 95% CI: 0.35 to 1.51) and prevent the development of overt HE (week 4: OR = 0.96, 95% CI: 0.17 to 5.44; week 12: OR = 2.7, 95% CI: 0.50 to 14.64) in patients with liver cirrhosis. However, lactulose appears to be more effective in reducing NCT values as compared to probiotics (week 4: MD = 6.7, 95% CI: 0.58 to 12.82). CONCLUSION Probiotics can decrease serum ammonia and endotoxin levels, improve MHE, and prevent overt HE development in patients with liver cirrhosis.
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Affiliation(s)
- Qing Cao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Cheng-Bo Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Shi-Gui Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Hong-Cui Cao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Ping Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Min Deng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Lan-Juan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Effect of probiotics and synbiotics consumption on serum concentrations of liver function test enzymes: a systematic review and meta-analysis. Eur J Nutr 2017; 57:2037-2053. [PMID: 29119235 DOI: 10.1007/s00394-017-1568-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 10/14/2017] [Indexed: 02/07/2023]
Abstract
PURPOSE The gut-liver interaction suggests that modification of gut bacterial flora using probiotics and synbiotics may improve liver function. This systematic review and meta-analysis aimed to clarify the effect of probiotics and synbiotics consumption on the serum concentration of liver function enzymes. METHODS PubMed (MEDLINE), Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library (Central) were searched from 1980 to August 2017 for studies where adults consumed probiotics and/or synbiotics in controlled trials and changes in liver function enzymes were examined. RESULTS A total of 17 studies (19 trials) were included in the meta-analysis. Random effects meta-analyses were applied. Probiotics and synbiotics significantly reduced serum alanine aminotransferase [- 8.05 IU/L, 95% confidence interval (CI) - 13.07 to - 3.04; p = 0.002]; aspartate aminotransferase (- 7.79 IU/L, 95% CI: - 13.93 to - 1.65; p = 0.02) and gamma-glutamyl transpeptidase (- 8.40 IU/L, 95% CI - 12.61 to - 4.20; p < 0.001). Changes in the serum concentration of alkaline phosphatase and albumin did not reach a statistically significant level. Changes to bilirubin levels were in favour of the control group (0.95 μmol/L, 95% CI 0.48-1.42; p < 0.001). Subgroup analysis suggested the existence of liver disease at baseline, synbiotics supplementation and duration of supplementation ≥ 8 weeks resulted in more pronounced improvement in liver function enzymes than their counterparts. CONCLUSIONS Probiotics and synbiotics may be suggested as supplements to improve serum concentration of liver enzymes, especially when synbiotics administered for a period ≥ 8 weeks and in individuals with liver disease.
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Zoumpopoulou G, Tsakalidou E, Thomas L. An Overview of Probiotic Research. PROBIOTIC DAIRY PRODUCTS 2017:293-357. [DOI: 10.1002/9781119214137.ch8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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The Effects of Probiotics and Symbiotics on Risk Factors for Hepatic Encephalopathy: A Systematic Review. J Clin Gastroenterol 2017; 51:312-323. [PMID: 28059938 DOI: 10.1097/mcg.0000000000000789] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Alterations in the levels of intestinal microbiota, endotoxemia, and inflammation are novel areas of interest in the pathogenesis of hepatic encephalopathy (HE). Probiotics and symbiotics are a promising treatment option for HE due to possible beneficial effects in modulating gut microflora and might be better tolerated and more cost-effective than the traditional treatment with lactulose, rifaximin or L-ornithine-L-aspartate. A systematic search of the electronic databases PubMed, ISI Web of Science, EMBASE, and Cochrane Library was conducted for randomized controlled clinical trials in adult patients with cirrhosis, evaluating the effect of probiotics and symbiotics in changes on intestinal microflora, reduction of endotoxemia, inflammation, and ammonia, reversal of minimal hepatic encephalopathy (MHE), prevention of overt hepatic encephalopathy (OHE), and improvement of quality of life. Nineteen trials met the inclusion criteria. Probiotics and symbiotics increased beneficial microflora and decreased pathogenic bacteria and endotoxemia compared with placebo/no treatment, but no effect was observed on inflammation. Probiotics significantly reversed MHE [risk ratio, 1.53; 95% confidence interval (CI): 1.14, 2.05; P=0.005] and reduced OHE development (risk ratio, 0.62; 95% CI: 0.48, 0.80; P=0.0002) compared with placebo/no treatment. Symbiotics significantly decreased ammonia levels compared with placebo (15.24; 95% CI: -26.01, -4.47; P=0.006). Probiotics did not show any additional benefit on reversal of MHE and prevention of OHE development when compared with lactulose, rifaximin, and L-ornithine-L-aspartate. Only 5 trials considered tolerance with minimal side effects reported. Although further research is warranted, probiotics and symbiotics should be considered as an alternative therapy for the treatment and management of HE given the results reported in this systematic review.
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Abstract
BACKGROUND Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live micro-organisms, which when administered in adequate amounts, may confer a health benefit on the host. OBJECTIVES To determine the beneficial and harmful effects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. SEARCH METHODS We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. SELECTION CRITERIA We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random-effects model meta-analysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration ranged from 10 days to 180 days. Eight trials declared their funding source, of which six were independently funded and two were industry funded. The remaining 13 trials did not disclose their funding source. We classified 19 of the 21 trials at high risk of bias.We found no effect on all-cause mortality when probiotics were compared with placebo or no treatment (7 trials; 404 participants; RR 0.58, 95% CI 0.23 to 1.44; low-quality evidence). No-recovery (as measured by incomplete resolution of symptoms) was lower for participants treated with probiotic (10 trials; 574 participants; RR 0.67, 95% CI 0.56 to 0.79; moderate-quality evidence). Adverse events were lower for participants treated with probiotic than with no intervention when considering the development of overt hepatic encephalopathy (10 trials; 585 participants; RR 0.29, 95% CI 0.16 to 0.51; low-quality evidence), but effects on hospitalisation and change of/or withdrawal from treatment were uncertain (hospitalisation: 3 trials, 163 participants; RR 0.67, 95% CI 0.11 to 4.00; very low-quality evidence; change of/or withdrawal from treatment: 9 trials, 551 participants; RR 0.70, 95% CI 0.46 to 1.07; very low-quality evidence). Probiotics may slightly improve quality of life compared with no intervention (3 trials; 115 participants; results not meta-analysed; low-quality evidence). Plasma ammonia concentration was lower for participants treated with probiotic (10 trials; 705 participants; MD -8.29 μmol/L, 95% CI -13.17 to -3.41; low-quality evidence). There were no reports of septicaemia attributable to probiotic in any trial.When probiotics were compared with lactulose, the effects on all-cause mortality were uncertain (2 trials; 200 participants; RR 5.00, 95% CI 0.25 to 102.00; very low-quality evidence); lack of recovery (7 trials; 430 participants; RR 1.01, 95% CI 0.85 to 1.21; very low-quality evidence); adverse events considering the development of overt hepatic encephalopathy (6 trials; 420 participants; RR 1.17, 95% CI 0.63 to 2.17; very low-quality evidence); hospitalisation (1 trial; 80 participants; RR 0.33, 95% CI 0.04 to 3.07; very low-quality evidence); intolerance leading to discontinuation (3 trials; 220 participants; RR 0.35, 95% CI 0.08 to 1.43; very low-quality evidence); change of/or withdrawal from treatment (7 trials; 490 participants; RR 1.27, 95% CI 0.88 to 1.82; very low-quality evidence); quality of life (results not meta-analysed; 1 trial; 69 participants); and plasma ammonia concentration overall (6 trials; 325 participants; MD -2.93 μmol/L, 95% CI -9.36 to 3.50; very low-quality evidence). There were no reports of septicaemia attributable to probiotic in any trial. AUTHORS' CONCLUSIONS The majority of included trials suffered from a high risk of systematic error ('bias') and a high risk of random error ('play of chance'). Accordingly, we consider the evidence to be of low quality. Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but probiotics may lead to little or no difference in mortality. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence is very low. High-quality randomised clinical trials with standardised outcome collection and data reporting are needed to further clarify the true efficacy of probiotics.
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Affiliation(s)
- Rohan Dalal
- Sydney Medical School, Westmead Hospital, Sydney, Australia
| | - Richard G McGee
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, Australia, 2145
| | - Stephen M Riordan
- Gastrointestinal and Liver Unit, The Prince of Wales, Barker St, Randwick, Australia, NSW 2031
| | - Angela C Webster
- Sydney School of Public Health, The University of Sydney, Edward Ford Building A27, Sydney, NSW, Australia, 2006
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Sharma BC, Singh J. Probiotics in management of hepatic encephalopathy. Metab Brain Dis 2016; 31:1295-1301. [PMID: 27121846 DOI: 10.1007/s11011-016-9826-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Accepted: 04/19/2016] [Indexed: 02/07/2023]
Abstract
Gut microflora leads to production of ammonia and endotoxins which play important role in the pathogenesis of hepatic encephalopathy (HE). There is relationship between HE and absorption of nitrogenous substances from the intestines. Probiotics play a role in treatment of HE by causing alterations in gut flora by decreasing the counts of pathogen bacteria, intestinal mucosal acidification, decrease in production and absorption of ammonia, alterations in permeability of gut, decreased endotoxin levels and changes in production of short chain fatty acids. Role of gut microbiota using prebiotics, probiotics and synbiotics have been evaluated in the management of minimal hepatic encephalopathy (MHE), overt HE and prevention of HE. Many studies have shown efficacy of probiotics in reduction of blood ammonia levels, treatment of MHE and prevention of HE. However these trials have problems like inclusion of small number of patients, short treatment durations, variability in HE/MHE related outcomes utilized and high bias risk, errors of systematic and random types. Systematic reviews also have shown different results with one systematic review showing clinical benefits whereas another concluded that probiotics do not have any role in treatment of MHE or HE. Also practical questions on optimal dose, ideal combination of organisms, and duration of treatment and persistence of benefits on long term follow-up are still to be clarified. At present, there are no recommendations for use of probiotics in patients with HE.
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Affiliation(s)
- Barjesh Chander Sharma
- Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, Room No. 203, Academic Block, New Delhi, 110002, India.
| | - Jatinderpal Singh
- Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, Room No. 203, Academic Block, New Delhi, 110002, India
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Saab S, Suraweera D, Au J, Saab EG, Alper TS, Tong MJ. Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials. Liver Int 2016; 36:986-93. [PMID: 26561214 DOI: 10.1111/liv.13005] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 11/02/2015] [Indexed: 12/27/2022]
Abstract
BACKGROUND Hepatic encephalopathy (HE) is a major complication of cirrhosis and is associated with decreased survival and increased health care utilization. AIM The aim of this study was to evaluate the efficacy of probiotics in the management minimal hepatic encephalopathy HE (MHE) and overt HE (OHE) in comparison to no treatment/placebo and lactulose. METHODS The main outcomes measured were mortality, improvement in MHE, progression to OHE in patients with MHE and hospitalization. We calculated odds ratios (OR) with 95% confidence intervals (CI). Study heterogeneity was assessed using the I(2) statistic. RESULTS Fourteen studies totalling 1152 patients were included in the analysis. The use of probiotics had no impact on the overall mortality when compared to either lactulose (OR: 1.07, 95% CI: 0.47-2.44, P = 0.88) or no treatment/placebo (OR: 0.69, 95% CI: 0.42-1.14, P = 0.15). When probiotics was compared to no treatment/placebo, it was associated with a significant improvement in MHE (OR: 3.91, 95% CI: 2.25-6.80, P < 0.00001), decreased hospitalization rates (OR: 0.53, 95% CI: 0.33-0.86, P = 0.01) and decreased progression to overt hepatic encephalopathy (OR: 0.40, 95% CI: 0.26-0.60, P < 0.0001). However when compared to lactulose, probiotics did not show a significant difference in improvement of MHE (OR: 0.81, 95% CI: 0.52-1.27, P = 0.35), hospitalization rates (OR: 1.02, 95% CI: 0.52-1.99, P = 0.96) or progression to overt hepatic encephalopathy (OR: 1.24, 95% CI 0.73-2.10, P = 0.42). CONCLUSIONS Overall the use of probiotics was more effective in decreasing hospitalization rates, improving MHE and preventing progression to OHE in patients with underlying MHE than placebo, but similar to that seen with lactulose. The use of probiotics did not affect mortality rates.
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Affiliation(s)
- Sammy Saab
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA.,Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | | | - Jennifer Au
- Department of Medicine, Albert Einstein Medical Center, Philadelphia, PA, USA
| | - Elena G Saab
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Tori S Alper
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Myron J Tong
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA.,Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.,Liver Center, Huntington Medical Research Institutes, Pasadena, CA, USA
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Abstract
Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD) encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration) approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed.
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Li F, Duan K, Wang C, McClain C, Feng W. Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms. Gastroenterol Res Pract 2015; 2016:5491465. [PMID: 26839540 PMCID: PMC4709639 DOI: 10.1155/2016/5491465] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 11/06/2015] [Accepted: 11/08/2015] [Indexed: 02/07/2023] Open
Abstract
Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD) encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration) approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed.
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Affiliation(s)
- Fengyuan Li
- College of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
- Departments of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA
| | - Kangmin Duan
- College of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China
| | - Cuiling Wang
- College of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
| | - Craig McClain
- Departments of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA
- Robley Rex Veterans Affairs Medical Center, Louisville, KY 40202, USA
| | - Wenke Feng
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
- Departments of Medicine, Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA
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Zhao LN, Yu T, Lan SY, Hou JT, Zhang ZZ, Wang SS, Liu FB. Probiotics can improve the clinical outcomes of hepatic encephalopathy: An update meta-analysis. Clin Res Hepatol Gastroenterol 2015; 39:674-82. [PMID: 25956487 DOI: 10.1016/j.clinre.2015.03.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Revised: 03/13/2015] [Accepted: 03/18/2015] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Although the efficacy of probiotics has been extensively studied in hepatic encephalopathy (HE), the results remain controversial. The objective of this study is to identify and update the association between probiotics and HE. METHODS Up to December 2014, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant articles about probiotics and HE. Jadad score was used to evaluate the quality of studies. Pooled relative risk (RR), publication bias and heterogeneity were assessed. RESULTS Nine studies met the inclusion criteria. Probiotics was associated with improvement of minimal HE and prophylaxis of overt HE [RR 1.52; 95% confidence intervals (95% CI) 1.00-2.33]. Studies with probiotics showed reduction of ammonia concentration [standard mean difference (SMD) -0.32, 95% CI -0.54 to -0.11]. Probiotics could reduce physical and psychosocial sickness impact profile (SIP) score with weight mean difference (WMD) -3.13 (95% CI -4.10 to -2.17) and WMD -3.50 (95% CI -4.91 to -2.08), respectively. Similar result was obtained with total SIP score (WMD -4.83; 95% CI -6.24 to -3.43). Reduction of severe adverse events, defined as minimal HE developing into overt HE, hospitalizations, infections or unrelated emergency room (ER) visits, was observed in HE with probiotics (RR 0.59; 95% CI 0.39-0.90). CONCLUSION Our pooled results indicated that probiotics was associated with improvement of minimal HE, prophylaxis of overt HE, and reduction of SIP score and severe adverse events. Large well-designed randomised controlled trials are needed to confirm these results.
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Affiliation(s)
- Li-Na Zhao
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Tao Yu
- Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Shao-Yang Lan
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiang-Tao Hou
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zheng-Zheng Zhang
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shuang-Shuang Wang
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Feng-Bin Liu
- Department of Gastroenterology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.
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Usami M, Miyoshi M, Yamashita H. Gut microbiota and host metabolism in liver cirrhosis. World J Gastroenterol 2015; 21:11597-11608. [PMID: 26556989 PMCID: PMC4631963 DOI: 10.3748/wjg.v21.i41.11597] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 08/06/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients.
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Clinical and pathophysiological consequences of alterations in the microbiome in cirrhosis. Am J Gastroenterol 2015; 110:1399-410; quiz 1411. [PMID: 26416191 DOI: 10.1038/ajg.2015.313] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2014] [Accepted: 08/04/2015] [Indexed: 02/06/2023]
Abstract
Cirrhosis is a major cause of mortality worldwide. Exponential rises in prevalence have been observed secondary to increases in obesity and alcohol consumption. Multiple lines of evidence implicate gut-derived bacteria and bacterial ligands as a central driver of pathogenesis. Recent developments in culture-independent techniques have facilitated a more accurate description of microbiome composition in cirrhosis and led to the description of measures of dysbiosis shown to be associated with disease. More importantly, metagenomic studies are adding to an understanding of the functional contribution of the microbiota and may prove to be a more clinically relevant biomarker than phylogenetic studies. Much like other dysbiotic states such as inflammatory bowel disease, the microbiota in cirrhosis is characterized by a low microbial and genetic diversity. Therapeutic strategies to diminish this process are currently limited to selective intestinal decontamination with antibiotics. This review summarizes the available data and develops a framework for the use of current and future treatment strategies to diminish the consequences of dysbiosis in cirrhosis. Interventional strategies to bind bacterial products in the gut lumen and blood, and modulate the magnitude of host sensing mechanisms remain an unmet clinical need. A greater understanding of the host-microbiota interaction in cirrhosis is of key importance to inform future interventional strategies to diminish the currently escalating burden of the disease.
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Chávez-Tapia NC, González-Rodríguez L, Jeong M, López-Ramírez Y, Barbero-Becerra V, Juárez-Hernández E, Romero-Flores JL, Arrese M, Méndez-Sánchez N, Uribe M. Current evidence on the use of probiotics in liver diseases. J Funct Foods 2015; 17:137-151. [DOI: 10.1016/j.jff.2015.05.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Van den Nieuwboer M, Brummer RJ, Guarner F, Morelli L, Cabana M, Claasen E. The administration of probiotics and synbiotics in immune compromised adults: is it safe? Benef Microbes 2015; 6:3-17. [PMID: 25304690 DOI: 10.3920/bm2014.0079] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This study aimed to systematically evaluate safety of probiotics and synbiotics in immune compromised adults (≥18 years). Safety was analysed using the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification, thereby providing an update on previous reports using the most recent available clinical data (2008-2013). Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 57 clinical studies indicates that probiotic and/or synbiotic administration in immune compromised adults is safe with regard to the current evaluated probiotic strains, dosages and duration. Individuals were considered immune compromised if HIV-infected, critically ill, underwent surgery or had an organ- or an autoimmune disease. There were no major safety concerns in the study, as none of the serious adverse events (AE)s were related, or suspected to be related, to the probiotic or synbiotic product and the study products were well tolerated. Overall, AEs occurred less frequent in immune compromised subjects receiving probiotics and/or synbiotics compared to the control group. In addition, the results demonstrated a flaw in precise reporting and classification of AE in most studies. Furthermore, generalisability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes. We argue that standardised reporting on adverse events (CTCAE) in 'food' studies should be obligatory, thereby improving reliability of data and re-enforcing the safety profile of probiotics.
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Affiliation(s)
- M Van den Nieuwboer
- Athena Institute, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, the Netherlands
| | - R J Brummer
- School of Health and Medical Sciences, Örebro University, 701 82 Örebro, Sweden
| | - F Guarner
- Food Microbiology and Biotechnology Digestive System Research Unit, CIBERehd, University Hospital Vall d'Hebron,, 08035 Barcelona, Spain
| | - L Morelli
- Istituto di Microbiologia Università Cattolica S.C.,, Via Emilia Parmense 84, 29122 Piacenza, Italy
| | - M Cabana
- Departments of Pediatrics, Epidemiology and Biostatistics, University of California San Francisco (UCSF), 3333 California Street, #245, San Francisco, CA 94118, USA
| | - E Claasen
- Athena Institute, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, the Netherlands Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands
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Lutz P, Nischalke HD, Strassburg CP, Spengler U. Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a cirrhotic liver. World J Hepatol 2015; 7:304-314. [PMID: 25848460 PMCID: PMC4381159 DOI: 10.4254/wjh.v7.i3.304] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/30/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023] Open
Abstract
Spontaneous bacterial peritonitis (SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotic treatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, non-absorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient’s site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.
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Aldridge DR, Tranah EJ, Shawcross DL. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation. J Clin Exp Hepatol 2015; 5:S7-S20. [PMID: 26041962 PMCID: PMC4442852 DOI: 10.1016/j.jceh.2014.06.004] [Citation(s) in RCA: 213] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Accepted: 06/05/2014] [Indexed: 12/12/2022] Open
Abstract
The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review.
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Key Words
- ATP, adenosine triphosphate
- AoCLF, acute-on-chronic liver failure
- BBB, blood–brain barrier
- CBF, cerebral blood flow
- CNS, central nervous system
- GS, glutamine synthetase
- HE, hepatic encephalopathy
- ICH, intracranial hypertension
- MHE, minimal hepatic encephalopathy
- MPT, mitochondrial permeability transition
- PAG, phosphate-activated glutaminase
- PTP, permeability transition pore
- TLR, toll-like receptor
- ammonia
- hepatic encephalopathy
- iNOS, inducible nitric oxide synthase
- infection
- inflammation
- systemic inflammatory response syndrome
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Affiliation(s)
| | | | - Debbie L. Shawcross
- Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
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Minemura M, Shimizu Y. Gut microbiota and liver diseases. World J Gastroenterol 2015; 21:1691-1702. [PMID: 25684933 PMCID: PMC4323444 DOI: 10.3748/wjg.v21.i6.1691] [Citation(s) in RCA: 126] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Revised: 01/08/2015] [Accepted: 01/21/2015] [Indexed: 02/06/2023] Open
Abstract
Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases.
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Moratalla A, Gómez-Hurtado I, Moya-Pérez Á, Zapater P, Peiró G, González-Navajas JM, Gómez Del Pulgar EM, Such J, Sanz Y, Francés R. Bifidobacterium pseudocatenulatum CECT7765 promotes a TLR2-dependent anti-inflammatory response in intestinal lymphocytes from mice with cirrhosis. Eur J Nutr 2015; 55:197-206. [DOI: 10.1007/s00394-015-0837-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Accepted: 01/12/2015] [Indexed: 12/13/2022]
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Short-term probiotic therapy alleviates small intestinal bacterial overgrowth, but does not improve intestinal permeability in chronic liver disease. Eur J Gastroenterol Hepatol 2014; 26:1353-9. [PMID: 25244414 DOI: 10.1097/meg.0000000000000214] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AIM : Although numerous animal studies suggest that probiotic therapy has beneficial effects in various liver diseases, the evidence for beneficial effects in human liver disease is controversial. This study was carried out to investigate the efficacy of probiotic therapy in alleviating small intestinal bacterial overgrowth (SIBO) and permeability in chronic liver disease. METHODS Fifty-three patients with chronic liver disease were randomized to either probiotic therapy or placebo. Six bacterial species were used: Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus. After 4 weeks, changes in the composition of fecal bacteria, SIBO, intestinal permeability, and clinical symptoms were examined. RESULTS Three of the six probiotic species, B. lactis, L. rhamnosus, and L. acidophilus, increased in the feces of the probiotic therapy group (P<0.001), whereas there was no change in fecal microbiota in the placebo group. SIBO disappeared in many individuals of the probiotic therapy group, but none in the placebo (24 vs. 0%, P<0.05). General gastrointestinal symptoms also improved more in the probiotic group and improvement in intestinal permeability was slightly but not significantly more frequent in the probiotic arm than the placebo arm (50 vs. 31.3%, P=0.248). Numbers of lactobacilli in stool were correlated negatively with intestinal permeability (P for trend<0.05). Liver chemistry did not improve significantly in either group. CONCLUSIONS We conclude that short-term probiotic administration in chronic liver disease is effective in alleviating SIBO and clinical symptoms, but ineffective in improving intestinal permeability and liver function.
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Gómez-Hurtado I, Such J, Sanz Y, Francés R. Gut microbiota-related complications in cirrhosis. World J Gastroenterol 2014; 20:15624-15631. [PMID: 25400446 PMCID: PMC4229527 DOI: 10.3748/wjg.v20.i42.15624] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota plays an important role in cirrhosis. The liver is constantly challenged with commensal bacteria and their products arriving through the portal vein in the so-called gut-liver axis. Bacterial translocation from the intestinal lumen through the intestinal wall and to mesenteric lymph nodes is facilitated by intestinal bacterial overgrowth, impairment in the permeability of the intestinal mucosal barrier, and deficiencies in local host immune defences. Deranged clearance of endogenous bacteria from portal and systemic circulation turns the gut into the major source of bacterial-related complications. Liver function may therefore be affected by alterations in the composition of the intestinal microbiota and a role for commensal flora has been evidenced in the pathogenesis of several complications arising in end-stage liver disease such as hepatic encephalopathy, splanchnic arterial vasodilatation and spontaneous bacterial peritonitis. The use of antibiotics is the main therapeutic pipeline in the management of these bacteria-related complications. However, other strategies aimed at preserving intestinal homeostasis through the use of pre-, pro- or symbiotic formulations are being studied in the last years. In this review, the role of intestinal microbiota in the development of the most frequent complications arising in cirrhosis and the different clinical and experimental studies conducted to prevent or improve these complications by modifying the gut microbiota composition are summarized.
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The overarching influence of the gut microbiome on end-organ function: the role of live probiotic cultures. Pharmaceuticals (Basel) 2014; 7:954-89. [PMID: 25244509 PMCID: PMC4190499 DOI: 10.3390/ph7090954] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Revised: 09/09/2014] [Accepted: 09/10/2014] [Indexed: 12/13/2022] Open
Abstract
At the time of birth, humans experience an induced pro-inflammatory beneficial event. The mediators of this encouraged activity, is a fleet of bacteria that assault all mucosal surfaces as well as the skin. Thus initiating effects that eventually provide the infant with immune tissue maturation. These effects occur beneath an emergent immune system surveillance and antigenic tolerance capability radar. Over time, continuous and regulated interactions with environmental as well as commensal microbial, viral, and other antigens lead to an adapted and maintained symbiotic state of tolerance, especially in the gastrointestinal tract (GIT) the organ site of the largest microbial biomass. However, the perplexing and much debated surprise has been that all microbes need not be targeted for destruction. The advent of sophisticated genomic techniques has led to microbiome studies that have begun to clarify the critical and important biochemical activities that commensal bacteria provide to ensure continued GIT homeostasis. Until recently, the GIT and its associated micro-biometabolome was a neglected factor in chronic disease development and end organ function. A systematic underestimation has been to undervalue the contribution of a persistent GIT dysbiotic (a gut barrier associated abnormality) state. Dysbiosis provides a plausible clue as to the origin of systemic metabolic disorders encountered in clinical practice that may explain the epidemic of chronic diseases. Here we further build a hypothesis that posits the role that subtle adverse responses by the GIT microbiome may have in chronic diseases. Environmentally/nutritionally/and gut derived triggers can maintain microbiome perturbations that drive an abnormal overload of dysbiosis. Live probiotic cultures with specific metabolic properties may assist the GIT microbiota and reduce the local metabolic dysfunctions. As such the effect may translate to a useful clinical treatment approach for patients diagnosed with a metabolic disease for end organs such as the kidney and liver. A profile emerges that shows that bacteria are diverse, abundant, and ubiquitous and have significantly influenced the evolution of the eukaryotic cell.
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Xu J, Ma R, Chen LF, Zhao LJ, Chen K, Zhang RB. Effects of probiotic therapy on hepatic encephalopathy in patients with liver cirrhosis: an updated meta-analysis of six randomized controlled trials. Hepatobiliary Pancreat Dis Int 2014; 13:354-60. [PMID: 25100119 DOI: 10.1016/s1499-3872(14)60280-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Liver cirrhotic patients with hepatic encephalopathy have poor prognosis. Probiotics alter the intestinal microbiota and reduce the production of ammonia. We conducted a meta-analysis about the role of probiotics on liver cirrhotic patients with hepatic encephalopathy. DATA SOURCES We collected the relevant literatures up to February 21, 2014 from databases of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. A statistical analysis was conducted by RevMan 5.2 and STATA 12.0 software. RESULTS Six randomized controlled trials involving 496 liver cirrhotic patients were included. The results showed that probiotic therapy significantly reduced the development of overt hepatic encephalopathy (OR [95% CI]: 0.42 [0.26, 0.70], P=0.0007). However, probiotics did not affect mortality, levels of serum ammonia and constipation (mortality: OR [95% CI]: 0.73 [0.38, 1.41], P=0.35; serum ammonia: WMD [95% CI]: -3.67 [-15.71, 8.37], P=0.55; constipation: OR [95% CI]: 0.67 [0.29, 1.56], P=0.35). CONCLUSION Probiotics decrease overt hepatic encephalopathy in patients with liver cirrhosis.
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Affiliation(s)
- Jun Xu
- Department of Surgery, Zhejiang University Hospital, Zhejiang University, Hangzhou 310027, China.
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Abstract
Cirrhosis can be sub-classified in clinical stages with distinct differences in prognosis and can even be reversed in some cases with successful etiological treatment. In this article, we review potential future therapies of cirrhosis, mainly focusing in the expansion of indications of currently licensed drugs. We strongly advocate that future therapies should focus on preventing the advent of complications and further progression of liver disease and should involve both primary and secondary care physicians. Such strategies could be based on the combination of currently licensed, relatively safe and inexpensive drugs and such randomized controlled trials should be prioritized in patients with advanced liver disease. The paradigm should be similar to that of prevention in cardiovascular diseases and long-term follow-up trials are needed.
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Affiliation(s)
- Emmanuel A Tsochatzis
- The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute of Liver and Digestive Health, London, UK
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Moratalla A, Gómez-Hurtado I, Santacruz A, Moya Á, Peiró G, Zapater P, González-Navajas JM, Giménez P, Such J, Sanz Y, Francés R. Protective effect of Bifidobacterium pseudocatenulatum CECT7765 against induced bacterial antigen translocation in experimental cirrhosis. Liver Int 2014; 34:850-8. [PMID: 24267920 DOI: 10.1111/liv.12380] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Accepted: 10/31/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Intervention in the gut ecosystem is considered as a potential strategy to treat liver diseases and their complications. We have evaluated the effects of Bifidobacterium pseudocatenulatum CECT7765 on bacterial translocation and the liver status in experimental cirrhosis. ANIMALS & METHODS Liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at week 12. One week prior to laparotomy, animals received B. pseudocatenulatum CECT7765 (10(9) cfu/daily) or placebo intragastrically. All animals received Escherichia coli (10(7) cfu/single dose) intragastrically 24 hours before laparotomy. A group of naïve non-treated animals was included as control. Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected. Liver histology, profibrogenic genes expression, bacterial DNA translocation, serum endotoxaemia and liver cytokine levels were measured. RESULTS Bifidobacterium pseudocatenulatum CECT7765 showed no significant effect on structural liver damage, as determined by histological evaluation, alpha-smooth muscle actin distribution, profibrogenic gene expression levels, total hydroxyproline levels and malon dialdehyde production compared with mice receiving placebo. Interestingly, bacterial DNA translocation and serum endotoxin levels were significantly decreased in mice receiving the Bifidobacterium strain compared with placebo. Gut barrier integrity markers were up-regulated in mice receiving B. pseudocatenulatum CECT7765 and quantitatively correlated with intestinal gene copy numbers of the bifidobacterial strain. Gene expression levels of several anti-inflammatory mediators were also increased in mice receiving B. pseudocatenulatum CECT7765 compared with placebo. CONCLUSION Oral administration of B. pseudocatenulatum CECT7765 is associated with improved gut barrier integrity and shows a beneficial effect against induced bacterial antigen translocation in the CCl4 -model of cirrhosis.
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Affiliation(s)
- Alba Moratalla
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Unidad Hepática, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain
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Gupta N, Kumar A, Sharma P, Garg V, Sharma BC, Sarin SK. Effects of the adjunctive probiotic VSL#3 on portal haemodynamics in patients with cirrhosis and large varices: a randomized trial. Liver Int 2013; 33:1148-57. [PMID: 23601333 DOI: 10.1111/liv.12172] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Accepted: 02/24/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Probiotics, by altering gut flora, may favourably alter portal haemodynamics in patients with cirrhosis. AIM To investigate the effect of probiotics on portal pressure in patients with cirrhosis. METHODS Randomized double-blind placebo-controlled trial conducted in G.B. Pant Hospital, New Delhi. A total of 94 cirrhotic patients having large oesophageal varices without history of variceal bleeding were randomized to three treatment groups and given 2 months' treatment with propranolol plus placebo, propranolol plus antibiotics (norfloxacin 400 mg BD) or propranolol plus probiotic (VSL#3, 900 billion/day) randomly assigned in 1:1:1 ratio. Outcome measures were change in Hepatic venous pressure gradient (HVPG): Response rate (Percentage of patients having a decrease from baseline of ≥20% or to ≤12 mm Hg) and changes from baseline; biochemical markers of inflammation: changes from baseline. RESULTS Adjunctive probiotics increased the response rate compared with propranolol alone (58% vs. 31%, P = 0.046), similar to adjunctive antibiotics (54%). The mean fall in HVPG was greater with either adjunctive probiotics (3.7 mm Hg vs. 2.1 mm Hg, P = 0.061) or adjunctive antibiotics (3.4 mm Hg) than with propranolol alone. Both adjunctive therapies were associated with greater decreases in TNF-α levels (in both peripheral and hepatic venous blood) that resulted from propranolol-only treatment. No clinically relevant between-group differences were observed in the type or frequency of adverse events. CONCLUSIONS Adjunctive probiotic (VSL#3) improved the response rate to propranolol therapy and was safe and well tolerated in patients with cirrhosis. Adjunctive probiotic therapy merits further study for reduction in portal pressure.
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Affiliation(s)
- Nitin Gupta
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
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Shang XJ. Effect of treatment with compound Lactobacillus acidophilus on complements and T lymphocyte subsets in patients with compensated liver cirrhosis. Shijie Huaren Xiaohua Zazhi 2013; 21:2446-2450. [DOI: 10.11569/wcjd.v21.i24.2446] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the effect of early oral compound Lactobacillus acidophilus on complements and T lymphocyte subsets in patients with compensated liver cirrhosis.
METHODS: Sixty-six patients with compensated liver cirrhosis were randomly divided into either a control group or a treatment group. The control group received conventional symptomatic treatment, while the treatment group was treated with compound Lactobacillus acidophilus (1.0 g, three times per day) for 12 wk on the basis of conventional symptomatic treatment. The changes in serum complements and T lymphocyte subsets between before and after treatment were observed and compared between the two groups of patients.
RESULTS: After treatment, the levels of complements C3 and C4 (0.97 g/L ± 0.16 g/L vs 0.85 g/L ± 0.24 g/L, 0.22 g/L ± 0.05 g/L vs 0.15 g/L ± 0.07 g/L, both P < 0.05) and the percentages of CD4+ and CD4+/CD8+ T lymphocyte subsets (37.9% ± 6.5% vs 33.8% ± 8.6%, 1.6% ± 0.5% vs 1.3% ± 0.7%, both P < 0.05) were significantly increased in the treatment group.
CONCLUSION: Oral compound Lactobacillus acidophilus can regulate intestinal flora imbalance and modulate immunity in patients with compensated liver cirrhosis.
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Abstract
There is a strong relationship between liver and gut; while the portal venous system receives blood from the gut, and its contents may affect liver functions, liver in turn, affects intestinal functions through bile secretion. There is robust evidence that the pathogenesis of hepatic encephalopathy (HE) is linked to alterations in gut microbiota and their by-products such as ammonia, indoles, oxindoles, endotoxins, etc. In the setting of intestinal barrier and immune dysfunction, these by-products are involved in the pathogenesis of complications of liver cirrhosis including HE and systemic inflammation plays an important role. Prebiotics, probiotics and synbiotics may exhibit efficacy in the treatment of HE by modulating the gut flora. They improve derangement in flora by decreasing the counts of pathogenic bacteria and thus improving the endotoxemia, HE and the liver disease. Current evidence suggest that the trials evaluating the role of probiotics in the treatment of HE are of not high quality and all trials had high risk of bias and high risk of random errors. Therefore, the use of probiotics for patients with HE cannot be currently recommended. Further RCTs are required. This review summarizes the main literature findings about the relationships between gut flora and HE, both in terms of the pathogenesis and the treatment of HE.
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Affiliation(s)
- Radha K Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
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