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Marino M, Mignozzi S, Michels KB, Cintolo M, Penagini R, Gargari G, Ciafardini C, Ferraroni M, Patel L, Del Bo' C, Leone P, Airoldi A, Vecchi M, Bonzi R, Oreggia B, Carnevali P, Vangeli M, Mutignani M, Guglielmetti S, Riso P, La Vecchia C, Rossi M. Serum zonulin and colorectal cancer risk. Sci Rep 2024; 14:28171. [PMID: 39548152 PMCID: PMC11568146 DOI: 10.1038/s41598-024-76697-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 10/16/2024] [Indexed: 11/17/2024] Open
Abstract
Intestinal permeability has been related to colorectal cancer (CRC) development. Zonulin, a protein able to regulate tight junction function and intestinal permeability, emerges as a promising marker to elucidate the contribution of bacterial translocation in CRC. An Italian case-control study included 77 CRC cases, 72 intestinal adenoma and 76 healthy controls (for a total of 148 tumor-free subjects), aged 20-85. Serum zonulin levels were quantified by ELISA kit and blood 16S rRNA gene copies by DNA extraction and polymerase chain reaction. We applied logistic regression models adjusted for center, sex, age and education. There was a positive association between zonulin and CRC risk. The odds ratio (OR) of CRC for the highest versus lowest tertile of zonulin as compared to tumor-free subjects was 2.36 (95% confidence interval, 1.14-4.86). The ORs were similar in colon and rectal cancers. The OR of colon cancer for the highest versus lowest levels of both zonulin and 16S rRNA gene copies was 4.55.Circulating levels of zonulin were higher in CRC patients compared to tumor-free controls supporting the hypothesis of an interplay of gut barrier dysfunction and bacterial translocation in colorectal carcinogenesis. Zonulin may interact with 16S rRNA gene copies and serve as a further biomarker in the evaluation of CRC diagnosis.
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Affiliation(s)
- Mirko Marino
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Silvia Mignozzi
- Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", Department of Clinical Sciences and Community Health, Department of Excellence 2023-2027, University of Milan, Milan, Italy
| | - Karin B Michels
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, USA
| | - Marcello Cintolo
- Digestive and Interventional Endoscopy Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Roberto Penagini
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giorgio Gargari
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | | | - Monica Ferraroni
- Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", Department of Clinical Sciences and Community Health, Department of Excellence 2023-2027, University of Milan, Milan, Italy
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy
| | - Linia Patel
- Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", Department of Clinical Sciences and Community Health, Department of Excellence 2023-2027, University of Milan, Milan, Italy
| | - Cristian Del Bo'
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Pierfrancesco Leone
- General Surgery Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Aldo Airoldi
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Maurizio Vecchi
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Rossella Bonzi
- Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", Department of Clinical Sciences and Community Health, Department of Excellence 2023-2027, University of Milan, Milan, Italy
| | - Barbara Oreggia
- General Surgery Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Pietro Carnevali
- Division of Minimally-invasive Surgical Oncology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Marcello Vangeli
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Massimiliano Mutignani
- Digestive and Interventional Endoscopy Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Simone Guglielmetti
- Department of Biotechnology and Biosciences (BtBs), University of Milan Biococca, Milan, Italy
| | - Patrizia Riso
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy.
| | - Carlo La Vecchia
- Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", Department of Clinical Sciences and Community Health, Department of Excellence 2023-2027, University of Milan, Milan, Italy
| | - Marta Rossi
- Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", Department of Clinical Sciences and Community Health, Department of Excellence 2023-2027, University of Milan, Milan, Italy.
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Miuma S, Miyaaki H, Taura N, Kanda Y, Matsuo S, Tajima K, Takahashi K, Nakao Y, Fukushima M, Haraguchi M, Sasaki R, Ozawa E, Ichikawa T, Nakao K. Elevated intestinal fatty acid-binding protein levels as a marker of portal hypertension and gastroesophageal varices in cirrhosis. Sci Rep 2024; 14:25003. [PMID: 39443545 PMCID: PMC11499902 DOI: 10.1038/s41598-024-76040-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 10/09/2024] [Indexed: 10/25/2024] Open
Abstract
We measured intestinal fatty acid-binding protein (I-FABP) levels, a useful marker of small intestinal mucosal injury, in patients with cirrhosis to determine their relationship with liver function and complications. This cross-sectional study included 71 patients with cirrhosis admitted for treatment of cirrhotic complications or hepatocellular carcinoma (cohort A) and 104 patients with cirrhosis who received direct-acting antiviral therapy for HCV (cohort B). I-FABP levels, measured by ELISA, were evaluated relative to hepatic reserve and compared with non-invasive scoring systems for diagnostic performance in cirrhotic complications. The median I-FABP level in both cohorts were significantly elevated in patients with reduced hepatic reserve (CTP grade A/BC cohort A, 2.33/3.17 ng/mL, p = 0.032; cohort B, 2.46/3.64 ng/mL, p = 0.008) and complications with gastroesophageal varices (GEV; GEV (-)/(+) cohort A, 1.66/3.67 ng/mL, p < 0.001; cohort B, 2.32/3.36 ng/mL; p = 0.003). Further, multiple logistic regression analysis identified I-FABP as the only factor contributing to GEV presence in both cohorts, which outperformed non-invasive scoring systems for GEV diagnosis (sensitivity 84.6%; specificity 84.2%; sensitivity 69.6%; specificity 63.8%, respectively). In conclusion, elevated small-intestinal mucosal injury in patients with cirrhosis was related to reduced hepatic reserve and GEV presence. I-FABP levels reflect portal hypertension and may be useful in cirrhosis management.
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Affiliation(s)
- Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan.
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Naota Taura
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Yasuko Kanda
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Satoshi Matsuo
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Kazuaki Tajima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Kosuke Takahashi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Yasuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Masanori Fukushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Masafumi Haraguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Eisuke Ozawa
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Tatsuki Ichikawa
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Shinti 6-39, Nagasaki, 850-8555, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1- 7-1 Sakamoto, Nagasaki, 852-8501, Japan
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Alhajaji R, Samkari MM, Althobaiti MA, Al-Ahmadi BR, Bugis AM, Bugis AM, Sabbagh FY, Althobaiti SA, Bukari AS, Alqurashi SM, Mshrai HA, Abdelwahab OA. Diabetes mellitus and the risk of spontaneous bacterial peritonitis in patients with liver cirrhosis: a systematic review and meta-analysis. Ann Saudi Med 2024; 44:272-287. [PMID: 39127903 PMCID: PMC11316951 DOI: 10.5144/0256-4947.2024.272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 07/05/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) represents a critical and potentially lethal condition that typically develops in individuals with liver cirrhosis. This meta-analysis aimed to assess diabetes mellitus (DM) as a risk factor for SBP in liver cirrhotic patients. METHODS Following PRISMA guidelines, fifteen studies were included, for a total of 76 815 patients. The risk of bias was assessed using the Newcastle-Ottawa scale (NOS). We represented the results as risk ratios (RR) with the corresponding 95% confidence intervals (CI) using RevMan software. Additionally, we pooled the hazard ratios (HR) for developing SBP in patients with DM from the included studies. RESULTS The meta-analysis shows a significantly increased risk of SBP in cirrhotic patients with DM (HR: 1.26; 95% CI [1.05-1.51], P=.01; HR: 1.70; 95% CI [1.32-2.18], P<.001). CONCLUSIONS The study signifies that DM is an independent risk factor for SBP, emphasizing the need for targeted preventive measures in this specific population.
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Affiliation(s)
- Raghad Alhajaji
- From the Department of Public Health, Makkah Branch of the Ministry of Health, Makkah, Saudi Arabia
- From the Primary Healthcare Centers, Makkah Health Clusters, Makkah, Saudi Arabia
| | | | - Mona A. Althobaiti
- From the Primary Healthcare Centers, Makkah Health Clusters, Makkah, Saudi Arabia
| | | | - Alaa Mohammed Bugis
- From the Primary Healthcare Centers, Makkah Health Clusters, Makkah, Saudi Arabia
| | - Amjad Mohammed Bugis
- From the College of Medicine and Surgery, Umm Al-Qura University, Makkah, Saudi Arabia
| | | | | | - Amro S. Bukari
- From the Primary Healthcare Centers, Makkah Health Clusters, Makkah, Saudi Arabia
| | | | - Hana Abdullah Mshrai
- From the Primary Healthcare Centers, Makkah Health Clusters, Makkah, Saudi Arabia
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Ramachandran G, Pottakkat B. Probiotics-A Promising Novel Therapeutic Approach in the Management of Chronic Liver Diseases. J Med Food 2024; 27:467-476. [PMID: 38574254 DOI: 10.1089/jmf.2023.k.0129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024] Open
Abstract
An increased incidence of liver diseases has been observed in recent years and is associated with gut dysbiosis, which causes bacterial infection, intestinal permeability, and further leads to disease-related complications. Probiotics, active microbial strains, are gaining more clinical importance due to their beneficial effect in the management of many diseases, including liver diseases. Clinical scenarios show strong evidence that probiotics have efficacy in treating liver diseases due to their ability to improve epithelial barrier function, prevent bacterial translocation, and boost the immune system. Moreover, probiotics survive both bile and gastric acid to reach the gut and exert their health benefit. Evidence shows that probiotics are a promising approach to prevent several complications in clinical practice. Herein, we discuss the recent evidence, challenges, and appropriate use of probiotics in managing advanced liver diseases, which may have an impact on future therapeutic strategies. Furthermore, the superior effect of strain-specific probiotics and their efficacy and safety in managing liver diseases are discussed.
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Affiliation(s)
- Gokulapriya Ramachandran
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Biju Pottakkat
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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Sanchez EM, Avery J, Gan J, Qian J, Mandal N, Agarwal A, Mwiinga M, Banda R, Darzi A, Kelly P, Thompson AJ. Transcutaneous fluorescence spectroscopy: development and characterization of a compact, portable, and fiber-optic sensor. JOURNAL OF BIOMEDICAL OPTICS 2024; 29:027003. [PMID: 38419754 PMCID: PMC10900991 DOI: 10.1117/1.jbo.29.2.027003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 10/27/2023] [Accepted: 01/04/2024] [Indexed: 03/02/2024]
Abstract
Significance The integrity of the intestinal barrier is gaining recognition as a significant contributor to various pathophysiological conditions, including inflammatory bowel disease, celiac disease, environmental enteric dysfunction (EED), and malnutrition. EED, for example, manifests as complex structural and functional changes in the small intestine leading to increased intestinal permeability, inflammation, and reduced absorption of nutrients. Despite the importance of gut function, current techniques to assess intestinal permeability (such as endoscopic biopsies or dual sugar assays) are either highly invasive, unreliable, and/or difficult to perform in certain patient populations (e.g., infants). Aim We present a portable, optical sensor based on transcutaneous fluorescence spectroscopy to assess gut function (in particular, intestinal permeability) in a fast and noninvasive manner. Approach Participants receive an oral dose of a fluorescent contrast agent, and a wearable fiber-optic probe detects the permeation of the contrast agent from the gut into the blood stream by measuring the fluorescence intensity noninvasively at the fingertip. We characterized the performance of our compact optical sensor by comparing it against an existing benchtop spectroscopic system. In addition, we report results from a human study in healthy volunteers investigating the impact of skin tone and contrast agent dose on transcutaneous fluorescence signals. Results The first study with eight healthy participants showed good correlation between our compact sensor and the existing benchtop spectroscopic system [correlation coefficient ( r ) > 0.919 , p < 0.001 ]. Further experiments in 14 healthy participants revealed an approximately linear relationship between the ingested contrast agent dose and the collected signal intensity. Finally, a parallel study on the impact of different skin tones showed no significant differences in signal levels between participants with different skin tones (p > 0.05 ). Conclusions In this paper, we demonstrate the potential of our compact transcutaneous fluorescence sensor for noninvasive monitoring of intestinal health.
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Affiliation(s)
- Elena Monfort Sanchez
- Institute of Global Health Innovation, Imperial College London, The Hamlyn Centre, London, United Kingdom
- St. Mary’s Hospital Campus, Imperial College London, Department of Surgery and Cancer, London, United Kingdom
| | - James Avery
- Institute of Global Health Innovation, Imperial College London, The Hamlyn Centre, London, United Kingdom
- St. Mary’s Hospital Campus, Imperial College London, Department of Surgery and Cancer, London, United Kingdom
| | - Jonathan Gan
- St. Mary’s Hospital Campus, Imperial College London, Department of Surgery and Cancer, London, United Kingdom
| | - Jingjing Qian
- Institute of Global Health Innovation, Imperial College London, The Hamlyn Centre, London, United Kingdom
| | - Nilanjan Mandal
- Institute of Global Health Innovation, Imperial College London, The Hamlyn Centre, London, United Kingdom
- St. Mary’s Hospital Campus, Imperial College London, Department of Surgery and Cancer, London, United Kingdom
| | - Arjun Agarwal
- St. Mary’s Hospital Campus, Imperial College London, Department of Surgery and Cancer, London, United Kingdom
| | - Mulima Mwiinga
- University of Zambia School of Medicine, Tropical Gastroenterology and Nutrition Group, Lusaka, Zambia
| | - Rose Banda
- University of Zambia School of Medicine, Tropical Gastroenterology and Nutrition Group, Lusaka, Zambia
| | - Ara Darzi
- Institute of Global Health Innovation, Imperial College London, The Hamlyn Centre, London, United Kingdom
- St. Mary’s Hospital Campus, Imperial College London, Department of Surgery and Cancer, London, United Kingdom
| | - Paul Kelly
- University of Zambia School of Medicine, Tropical Gastroenterology and Nutrition Group, Lusaka, Zambia
- Queen Mary University of London, Blizard Institute, London, United Kingdom
| | - Alex J. Thompson
- Institute of Global Health Innovation, Imperial College London, The Hamlyn Centre, London, United Kingdom
- St. Mary’s Hospital Campus, Imperial College London, Department of Surgery and Cancer, London, United Kingdom
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Esparteiro D, Fouquet G, Courtois A, Jedraszak G, Marticho L, Gourdel M, Billon-Crossouard S, Croyal M, Naassila M, Nguyen-Khac E, Marcq I. Serum bile acids profiles are altered without change of the gut microbiota composition following a seven-day prednisolone therapy in severe alcoholic hepatitis. Gut Microbes 2024; 16:2382767. [PMID: 39078043 PMCID: PMC11290774 DOI: 10.1080/19490976.2024.2382767] [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: 04/26/2024] [Revised: 06/05/2024] [Accepted: 07/17/2024] [Indexed: 07/31/2024] Open
Abstract
Severe Alcoholic Hepatitis (sAH) is an acute form of liver injury caused by chronic and heavy alcohol drinking. A one-month corticosteroids course is the only sAH reference treatment, and its interactions with the Gut Microbiota (GM), which is a key contributor to liver injury, remain unknown. To evaluate the evolution of the GM in sAH patients, we retrospectively investigated the composition of the GM of 27 sAH patients at the Amiens University Hospital before (D0) and after (D7) a 7-day corticotherapy course using fecal metagenomics sequencing. We also quantified fecal Short-Chain Fatty Acids (SCFA) and fecal and serum Bile Acids (BA), as well as serum Lipopolysaccharide-Binding Protein (LBP). Overall, the community and taxonomical analyses did not reveal any GM evolution between D0 and D7, nor did the SCFA profiles analysis. However, in serum but not fecal samples, the ratio of glyco-conjugated to tauro-conjugated BA was significantly reduced at D7, independently of the response to treatment, while two BA were enriched in non-responder patients. LBP concentration significantly diminished between D0 and D7, which may indicate an improvement of the gut barrier. The stability of the GM of sAH is interesting in the perspective of new treatments based on GM modulation.
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Affiliation(s)
- Damien Esparteiro
- GRAP INSERM U1247, Universite de Picardie Jules Verne, Amiens, France
| | - Grégory Fouquet
- GRAP INSERM U1247, Universite de Picardie Jules Verne, Amiens, France
| | - Anoïsia Courtois
- GRAP INSERM U1247, Universite de Picardie Jules Verne, Amiens, France
| | | | - Léa Marticho
- CHU d’Amiens, Service d’Hépato-Gastro-Entérologie, Amiens, France
| | - Mathilde Gourdel
- CHU Nantes, CNRS, INSERM, BioCore, US16, SFR Bonamy, Nantes Université, Nantes, France
| | | | - Mikaël Croyal
- CHU Nantes, CNRS, INSERM, BioCore, US16, SFR Bonamy, Nantes Université, Nantes, France
- CRNH-Ouest Mass Spectrometry Core Facility, Nantes, France
- CNRS, INSERM, l’Institut du Thorax, Nantes Université, Nantes, France
| | - Mickaël Naassila
- GRAP INSERM U1247, Universite de Picardie Jules Verne, Amiens, France
| | - Eric Nguyen-Khac
- GRAP INSERM U1247, Universite de Picardie Jules Verne, Amiens, France
- CHU d’Amiens, Service d’Hépato-Gastro-Entérologie, Amiens, France
| | - Ingrid Marcq
- GRAP INSERM U1247, Universite de Picardie Jules Verne, Amiens, France
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Maslennikov R, Poluektova E, Zolnikova O, Sedova A, Kurbatova A, Shulpekova Y, Dzhakhaya N, Kardasheva S, Nadinskaia M, Bueverova E, Nechaev V, Karchevskaya A, Ivashkin V. Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis. Int J Mol Sci 2023; 24:16502. [PMID: 38003692 PMCID: PMC10671141 DOI: 10.3390/ijms242216502] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/11/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open
Abstract
Cirrhosis is the end result of liver fibrosis in chronic liver diseases. Studying the mechanisms of its development and developing measures to slow down and regress it based on this knowledge seem to be important tasks for medicine. Currently, disorders of the gut-liver axis have great importance in the pathogenesis of cirrhosis. However, gut dysbiosis, which manifests as increased proportions in the gut microbiota of Bacilli and Proteobacteria that are capable of bacterial translocation and a decreased proportion of Clostridia that strengthen the intestinal barrier, occurs even at the pre-cirrhotic stage of chronic liver disease. This leads to the development of bacterial translocation, a process by which those microbes enter the blood of the portal vein and then the liver tissue, where they activate Kupffer cells through Toll-like receptor 4. In response, the Kupffer cells produce profibrogenic cytokines, which activate hepatic stellate cells, stimulating their transformation into myofibroblasts that produce collagen and other elements of the extracellular matrix. Blocking bacterial translocation with antibiotics, probiotics, synbiotics, and other methods could slow down the progression of liver fibrosis. This was shown in a number of animal models but requires further verification in long-term randomized controlled trials with humans.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119048 Moscow, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119048 Moscow, Russia
| | - Oxana Zolnikova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Alla Sedova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Anastasia Kurbatova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Yulia Shulpekova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Natyia Dzhakhaya
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Svetlana Kardasheva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Maria Nadinskaia
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Elena Bueverova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Vladimir Nechaev
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Anna Karchevskaya
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119048 Moscow, Russia
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Zhang Y, Aldamarany WAS, Deng L, Zhong G. Carbohydrate supplementation retains intestinal barrier and ameliorates bacterial translocation in an antibiotic-induced mouse model. Food Funct 2023; 14:8186-8200. [PMID: 37599609 DOI: 10.1039/d3fo01343j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2023]
Abstract
Bacterial translocation (BT), with antibiotic use as an inducer, is associated with increased risk of developing multiple inflammatory disorders, and is closely associated with intestinal barrier integrity. Deacetylated konjac glucomannan (DKGM) and konjac oligo-glucomannan (KOGM) are two of the most widely used derivatives in the food industry. They are structurally and physiologically distinct from konjac glucomannan (KGM), and previous studies have confirmed their prebiotic effects. But whether they play a role in antibiotic-induced BT is unknown. Here, we applied an antibiotic cocktail (Abx) to a mouse model and investigated whether and how KGM and its derivatives function in BT and inflammation response amelioration during and after antibiotics, and which intervention plan is more effective. The results showed that KGM and its derivatives all inhibited BT. The colon tissue lesions caused by BT were largely alleviated, and short-chain fatty acid (SCFA) production was highly improved with the supplementation of carbohydrates. The prolonged intervention plan using KGM and its derivatives was more efficient than intervention only during the Abx administration period. Among the three dietary fibers, KGM behaved best, while DKGM and KOGM behaved equivalently. Additionally, KGM and its derivatives all reduced the inflammatory response accompanying BT, but DKGM may have a direct inhibitory efficacy in inflammation other than that through IL-10, unlike KGM or KOGM.
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Affiliation(s)
- Yuan Zhang
- College of Food Science, Southwest University, Chongqing, 400715, China.
- Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing, Southwest University, Chongqing, 400715, China
| | - Waleed A S Aldamarany
- College of Food Science, Southwest University, Chongqing, 400715, China.
- Food Science and Technology Department, Faculty of Agriculture, Al-Azhar University (Assiut Branch), Assiut 71524, Egypt
| | - Liling Deng
- Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China
| | - Geng Zhong
- College of Food Science, Southwest University, Chongqing, 400715, China.
- Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing, Southwest University, Chongqing, 400715, China
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9
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Stojic J, Kukla M, Grgurevic I. The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status. Diagnostics (Basel) 2023; 13:2960. [PMID: 37761327 PMCID: PMC10528663 DOI: 10.3390/diagnostics13182960] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/06/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.
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Affiliation(s)
- Josip Stojic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, 10000 Zagreb, Croatia;
| | - Michał Kukla
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagellonian University Medical College, 31-688 Kraków, Poland;
- Department of Endoscopy, University Hospital, 30-688 Kraków, Poland
| | - Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, 10000 Zagreb, Croatia;
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
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10
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Cooper KM, Colletta A, Moulton K, Ralto KM, Devuni D. Kidney disease in patients with chronic liver disease: Does sex matter? World J Clin Cases 2023; 11:3980-3992. [PMID: 37388789 PMCID: PMC10303604 DOI: 10.12998/wjcc.v11.i17.3980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/30/2023] [Accepted: 05/16/2023] [Indexed: 06/12/2023] Open
Abstract
Kidney disease in patients with liver disease is serious and increases mortality. Up to 50% of patients hospitalized experience an episode of acute kidney injury. In general, men with liver disease are thought to be at increased risk of kidney disease. However, this association should be considered with caution because most studies use creatinine-based inclusion criteria, which is negatively biased against women. In this review, we synthesize data on sex differences in kidney disease in patients with chronic liver disease in the clinical setting and discuss potential physiologic underpinnings.
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Affiliation(s)
- Katherine M Cooper
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Alessandro Colletta
- Department of Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Kristen Moulton
- Department of Medicine, Division of Gastroenterology, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Kenneth M Ralto
- Department of Medicine, Division of Renal Medicine, UMass Chan Medical School, Worcester, MA 01665, United States
| | - Deepika Devuni
- Department of Medicine, Division of Gastroenterology, UMass Chan Medical School, Worcester, MA 01665, United States
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11
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Wang JS, Liu JC. Intestinal microbiota in the treatment of metabolically associated fatty liver disease. World J Clin Cases 2022; 10:11240-11251. [PMID: 36387806 PMCID: PMC9649557 DOI: 10.12998/wjcc.v10.i31.11240] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/07/2022] [Accepted: 09/27/2022] [Indexed: 02/05/2023] Open
Abstract
Metabolically associated fatty liver disease (MAFLD) is a common cause of chronic liver disease, the hepatic manifestation of metabolic syndrome. Despite the increasing incidence of MAFLD, no effective treatment is available. Recent research indicates a link between the intestinal microbiota and liver diseases such as MAFLD. The composition and characteristics of the intestinal microbiota and therapeutic perspectives of MAFLD are reviewed in the current study. An imbalance in the intestinal microbiota increases intestinal permeability and exposure of the liver to adipokines. Furthermore, we focused on reviewing the latest "gut-liver axis" targeted therapy.
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Affiliation(s)
- Ji-Shuai Wang
- Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Jin-Chun Liu
- Department of Gastroenterology, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
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12
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Garbuzenko DV. Pathophysiological Prerequisites and Therapeutic Potential of Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis. THE RUSSIAN ARCHIVES OF INTERNAL MEDICINE 2022; 12:352-362. [DOI: 10.20514/2226-6704-2022-12-5-352-362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
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13
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Sun X, Shi J, Kong L, Shen Q, Zeng X, Wu Z, Guo Y, Pan D. Recent insights into the hepatoprotective effects of lactic acid bacteria in alcoholic liver disease. Trends Food Sci Technol 2022. [DOI: 10.1016/j.tifs.2022.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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14
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Szabo G, Thursz M, Shah VH. Therapeutic advances in alcohol-associated hepatitis. J Hepatol 2022; 76:1279-1290. [PMID: 35589250 DOI: 10.1016/j.jhep.2022.03.025] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/03/2022] [Accepted: 03/24/2022] [Indexed: 02/07/2023]
Abstract
In recent years, there have been important advances in our understanding of alcohol-associated hepatitis (AH), which have occurred in parallel with a surge in clinical trial activity. Meanwhile, the broader medical field has seen a transformation in care paradigms based on emerging digital technologies. This review focuses on breakthroughs in our understanding of AH and how these breakthroughs are leading to new paradigms for biomarker discovery, clinical trial activity, and care models for patients. It portends a future in which multimodal data from genetic, radiomic, histologic, and environmental sources can be integrated and synthesised to generate personalised biomarkers and therapies for patients with AH.
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Affiliation(s)
- Gyongyi Szabo
- Carol M. Gatton Chairman of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Mark Thursz
- Division of Digestive Diseases, Imperial College, London, UK.
| | - Vijay H Shah
- Mitchell T. Rabkin, M.D. Chair, Professor of Medicine, Harvard Medical School, Chief Academic Officer, Beth Israel Deaconess Medical Center and Beth Israel Lahey Health, Boston, MA, USA
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15
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Koepf US, Scheidt S, Hischebeth GTR, Strassburg CP, Wirtz DC, Randau TM, Lutz P. Increased rate of enteric bacteria as cause of periprosthetic joint infections in patients with liver cirrhosis. BMC Infect Dis 2022; 22:389. [PMID: 35439971 PMCID: PMC9019970 DOI: 10.1186/s12879-022-07379-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 04/08/2022] [Indexed: 11/12/2022] Open
Abstract
Introduction Periprosthetic joint infections (PJI) are a major complication in joint-arthroplasty. Rifampicin is often used as an additional agent to treat PJI, because it penetrates bacterial biofilms. However, rifaximin, belonging to the same antibiotic class as rifampicin, is frequently used to prevent episodes of hepatic encephalopathy in patients with cirrhosis and may induce resistance to rifampicin. The aim of this study was to examine the microbial pattern of periprosthetic joint infections in cirrhotic patients and to test the hypothesis that intake of rifaximin increases the rate of resistance to rifampicin in periprosthetic joint infections. Methods A cohort of cirrhotic patients and PJI (n = 25) was analysed on the characteristics of bacterial isolates from sonication and tissue analysis. In a second step a subgroup analysis on the development of rifampicin resistant bacterial specimens, depending on the intake of rifaximin (8 rifaximin intake patients vs. 13 non rifaximin intake patients) was performed. Results Intestinal bacteria were found in 50% of the specimens, which was significantly more frequent than in a control cohort. By comparison of the single bacterial isolates, rifampicin resistance was detected in 69.2% (9/13) of the rifaximin-intake samples. In contrast, the non-rifaximin-intake isolates only were resistant to rifampicin in 22.2% (4/18) of the cases (p = 0.01). The odds ratio for developing a rifampicin-resistance through rifaximin intake was calculated as OR = 13.5. Conclusion Periprosthetic joint infections have a high incidence of being caused by enteric bacteria in cirrhotic patients. Due to this change in microbial pattern and the innate resistance to rifampicin of most of gram-negative bacteria, the therapy with rifampicin should be carefully considered. The association between the use of rifaximin and developed resistance to rifampicin has a major impact on the treatment of PJI.
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Affiliation(s)
- Uta S Koepf
- Department of Internal Medicine I, University Hospital Bonn, Venusberg Campus 1, 53127, Bonn, Germany.
| | - Sebastian Scheidt
- Department of Orthopaedics and Traumatology, University Hospital Bonn, Bonn, Germany
| | - Gunnar T R Hischebeth
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University Hospital Bonn, Venusberg Campus 1, 53127, Bonn, Germany
| | - Dieter C Wirtz
- Department of Orthopaedics and Traumatology, University Hospital Bonn, Bonn, Germany
| | - Thomas M Randau
- Department of Orthopaedics and Traumatology, University Hospital Bonn, Bonn, Germany
| | - Philipp Lutz
- Department of Internal Medicine I, University Hospital Bonn, Venusberg Campus 1, 53127, Bonn, Germany
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16
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Stepanova N. How Advanced Is Our Understanding of the Role of Intestinal Barrier Dysfunction in the Pathogenesis of Recurrent Urinary Tract Infections. Front Pharmacol 2022; 13:780122. [PMID: 35359839 PMCID: PMC8960443 DOI: 10.3389/fphar.2022.780122] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 02/24/2022] [Indexed: 12/12/2022] Open
Abstract
A comprehensive understanding of urinary tract infections (UTIs), one of the most common human infections, is required as they are complex and poorly understood diseases. Periurethral and vaginal colonization by rectal flora, with the constant presence of pathogens in the urethra, is the initial step of the recurrent UTIs pathway. Current scientific data describe the genetic, etiological, biological, and behavioral risk factors for recurring UTIs, but they do not include the effect of intestinal barrier function on the disease. Although gut microbiota has been proposed as the main source for UTIs, the cross-talk between intestinal barrier dysfunction and the recurrence of UTIs has not yet been supported by scientific data. In this opinion review, based on published data and the results of our clinical studies, I aimed to outline the possible contribution of intestinal barrier dysfunction to the pathogenesis of recurrent UTIs. I believe that the unanswered questions raised by this review can guide further experimental and controlled studies to clarify the mechanisms underlying the role of intestinal barrier dysfunction in the pathogenesis of recurrent UTIs.
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Affiliation(s)
- Natalia Stepanova
- State Institution “Institute of Nephrology National Academy of Medical Science of Ukraine”, Kyiv, Ukraine
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17
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Green PG, Alvarez P, Levine JD. Probiotics attenuate alcohol-induced muscle mechanical hyperalgesia: Preliminary observations. Mol Pain 2022; 18:17448069221075345. [PMID: 35189754 PMCID: PMC8874179 DOI: 10.1177/17448069221075345] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Alcohol use disorder (AUD) is a major health problem that causes millions of deaths annually world-wide. AUD is considered to be a chronic pain disorder, that is exacerbated by alcohol withdrawal, contributing to a high (∼80%) relapse rate. Chronic alcohol consumption has a marked impact on the gut microbiome, recognized to have a significant effect on chronic pain. We tested the hypothesis that modulating gut microbiota through feeding rats with probiotics can attenuate alcohol-induced muscle mechanical hyperalgesia. To test this hypothesis, rats were fed alcohol (6.5%, 4 days on 3 days off) for 3 weeks, which induced skeletal muscle mechanical hyperalgesia. Following alcohol feeding, at which time nociceptive thresholds were ∼37% below pre-alcohol levels, rats received probiotics in their drinking water, either Lactobacillus Rhamnosus GG (Culturelle) or De Simone Formulation (a mixture of 8 bacterial species) for 8 days; control rats received plain water to drink. When muscle mechanical nociceptive threshold was evaluated 1 day after beginning probiotic feeding, nociceptive thresholds were significantly higher than rats not receiving probiotics. Mechanical nociceptive thresholds continued to increase during probiotic feeding, with thresholds approaching pre-alcohol levels 5 days after starting probiotics; nociceptive threshold in rats not receiving probiotics remained low. After probiotics were removed from the drinking water, nociceptive thresholds gradually decreased in these two groups, although they remained higher than the group not treated with probiotic (21 days after ending alcohol feeding). These observations suggest that modification of gut microbiota through probiotic feeding has a marked effect on chronic alcohol-induced muscle mechanical hyperalgesia. Our results suggest that administration of probiotics to individuals with AUD may reduce pain associated with alcohol consumption and withdrawal, and may be a novel therapeutic intervention to reduce the high rate of relapse seen in individuals with AUD attempting to abstain from alcohol.
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Affiliation(s)
- Paul G Green
- Departments of Oral and Maxillofacial Surgery, 8785University of California San Francisco, San Francisco, CA, USA.,Departments of Preventative and Restorative Dental Sciences, 8785University of California San Francisco, San Francisco, CA, USA.,Division of Neuroscience, 8785University of California San Francisco, San Francisco, CA, USA
| | - Pedro Alvarez
- Departments of Oral and Maxillofacial Surgery, 8785University of California San Francisco, San Francisco, CA, USA.,Division of Neuroscience, 8785University of California San Francisco, San Francisco, CA, USA
| | - Jon D Levine
- Departments of Oral and Maxillofacial Surgery, 8785University of California San Francisco, San Francisco, CA, USA.,Division of Neuroscience, 8785University of California San Francisco, San Francisco, CA, USA.,Departments of Medicine, 8785University of California San Francisco, San Francisco, CA, USA
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18
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Thanapirom K, Teerasarntipan T, Treeprasertsuk S, Choudhury A, Sahu MK, Maiwall R, Pamecha V, Moreau R, Al Mahtab M, Chawla YK, Devarbhavi H, Yu C, Ning Q, Amarapurkar D, Eapen CE, Hamid SS, Butt AS, Kim DJ, Lee GH, Sood A, Lesmana LA, Abbas Z, Shiha G, Payawal DA, Yuen MF, Chan A, Lau G, Jia J, Rahman S, Sharma BC, Yokosuka O, Sarin SK. Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure. Hepatol Int 2022; 16:171-182. [PMID: 34822057 PMCID: PMC8844167 DOI: 10.1007/s12072-021-10266-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 10/24/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. METHODS A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. RESULTS Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36-0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43-0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. CONCLUSIONS The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.
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Affiliation(s)
- Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Thai Red Cross, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Pathumwan, Bangkok, Thailand
- Liver Fibrosis and Cirrhosis Research Unit, Chulalongkorn University, Bangkok, Thailand
| | - Tongluk Teerasarntipan
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Thai Red Cross, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Pathumwan, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Thai Red Cross, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Pathumwan, Bangkok, Thailand.
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, India
| | - Viniyendra Pamecha
- Department of Liver Transplantation and Hepato Pancreatico Biliary Surgery, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Richard Moreau
- EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
- Inserm, U1149, Centre de Recherche Sur L'Inflammation (CRI),, Paris, France
- UMRS1149, Université de Paris, Paris, France
- Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Mamun Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | | | | | - Chen Yu
- Beijing Youan Hospital and Translational Hepatology Institute, Beijing, China
| | - Qin Ning
- Tongji Hospital, Tongji Medical College, Wuhan, China
| | - Deepak Amarapurkar
- Department of Gastroenterology, Bombay Hospital and Medical Research Centre, Mumbai, India
| | | | | | | | - Dong Joon Kim
- Hallym University College of Medicine, Chuncheon, South Korea
| | - Guan H Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ajit Sood
- Dayanand Medical College, Ludhiana, India
| | | | | | - Gamal Shiha
- Egyptian Liver Research Institute and Hospital, Cairo, Egypt
| | | | - Man-Fung Yuen
- Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Albert Chan
- Queen Mary Hospital, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - George Lau
- Department of Medicine, Humanity and Health Medical Group, New Kowloon, Hongkong, China
| | - Jidong Jia
- Friendship Hospital, Capital University, Beijing, China
| | - Salimur Rahman
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Barjesh C Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Acharya Shree Tulsi Marg, Vasant Kunj, New Delhi, 110070, India
- Department of Advanced Endoscopy, Institute of Liver and Biliary Sciences, D-1, Acharya Shree Tulsi Marg, Vasant Kunj, New Delhi, 110070, India
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19
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Sun Z, Song ZG, Liu C, Tan S, Lin S, Zhu J, Dai FH, Gao J, She JL, Mei Z, Lou T, Zheng JJ, Liu Y, He J, Zheng Y, Ding C, Qian F, Zheng Y, Chen YM. Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients. BMC Med 2022; 20:24. [PMID: 35045853 PMCID: PMC8769945 DOI: 10.1186/s12916-021-02212-0] [Citation(s) in RCA: 101] [Impact Index Per Article: 33.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 12/09/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology. METHODS To better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients. RESULTS Altered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients. CONCLUSIONS Our results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.
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Affiliation(s)
- Zhonghan Sun
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.,Ministry of Education Key Laboratory of Contemporary Anthropology, Fudan University, Shanghai, China
| | - Zhi-Gang Song
- Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Chenglin Liu
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Shishang Tan
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Shuchun Lin
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Jiajun Zhu
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Fa-Hui Dai
- Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Jian Gao
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Jia-Lei She
- Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Zhendong Mei
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Tao Lou
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Jiao-Jiao Zheng
- Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Yi Liu
- Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Jiang He
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Yuanting Zheng
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Chen Ding
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Feng Qian
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China
| | - Yan Zheng
- State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China. .,Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, China.
| | - Yan-Mei Chen
- Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.
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20
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Maslennikov R, Ivashkin V, Efremova I, Poluektova E, Shirokova E. Gut-liver axis in cirrhosis: Are hemodynamic changes a missing link? World J Clin Cases 2021; 9:9320-9332. [PMID: 34877269 PMCID: PMC8610853 DOI: 10.12998/wjcc.v9.i31.9320] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 06/03/2021] [Accepted: 09/07/2021] [Indexed: 02/06/2023] Open
Abstract
Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease, especially cirrhosis. This introduces the concept of the gut-liver axis, which can be imagined as a chain connected by several links. Gut dysbiosis, small intestinal bacterial overgrowth, and intestinal barrier alteration lead to bacterial translocation, resulting in systemic inflammation. Systemic inflammation further causes vasodilation, arterial hypotension, and hyperdynamic circulation, leading to the aggravation of portal hypertension, which contributes to the development of complications of cirrhosis, resulting in a poorer prognosis. The majority of the data underlying this model were obtained initially from animal experiments, and most of these correlations were further reproduced in studies including patients with cirrhosis. However, despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development, the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied. They remain a missing link in the gut-liver axis and a challenge for future research.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization "Scientific Community for the Promotion of the Clinical Study of the Human Microbiome", Moscow 119435, Russia
- Department of Internal Medicine, Consultative and Diagnostic Center of the Moscow City Health Department, Moscow 107564, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Interregional Public Organization "Scientific Community for the Promotion of the Clinical Study of the Human Microbiome", Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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