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1
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Nie P, Hu L, You T, Jia T, Xu H. Lead Mediated Lipopolysaccharides Exacerbates Fatty Liver Processes in High-Fat Diets-Induced Mice. ENVIRONMENTAL TOXICOLOGY 2025; 40:750-763. [PMID: 39715151 DOI: 10.1002/tox.24463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 10/10/2024] [Accepted: 12/08/2024] [Indexed: 12/25/2024]
Abstract
Obesity leads to a variety of health risks, and lead, which is ranked second in Agency for Toxic Substances and Disease Registry's priority list of harmful substances, may be more harmful to individuals that are obese. C57BL/6 mice were fed a normal diet or a high-fat diet with or without exposure to 1 g/L lead exposure in drinking water for 8 consecutive weeks. Serum and hepatic biochemistry analysis, histopathological observation, and RT-qPCR were used to explore the potential mechanism of liver damage in obese individuals after Pb exposure, and fecal microbiota transplantation was performed to investigate the role of the gut microbiota in the progression of fatty liver disease. We found that the progression of fatty liver disease induced by high-fat diets was accelerated by chronic lead intake. In addition, the occurrences of liver injury in recipient mice suggested the role of the gut microbiota. These findings indicated that the combination of lead and a HFD exacerbated hepatic lipotoxicity by activating LPS-mediated inflammation, and that gut microbiota disorders and impaired intestinal barrier function play pivotal roles in the progression of fatty liver disease.
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Affiliation(s)
- Penghui Nie
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
| | - Liehai Hu
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
| | - Tao You
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
| | - Tiantian Jia
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
| | - Hengyi Xu
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China
- International Institute of Food Innovation co. Ltd., Nanchang University, Nanchang, People's Republic of China
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2
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Zhu Y, Zhang X, Huang W, Luo M, Feng X, Zhang H, Qi Q. Protective Effect of Enterococcus faecium Against Alcohol-Induced Acute Liver Injury Via Extracellular Vesicles in Rats. Foodborne Pathog Dis 2025. [PMID: 40256984 DOI: 10.1089/fpd.2025.0005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/22/2025] Open
Abstract
The beneficial effects of probiotics on alcohol-induced liver injury have been studied, but the mechanisms by which Enterococcus regulates liver function are still under investigation. In this study, we examined Enterococcus faecium (Efm) and E. faecium-derived extracellular vesicles (EfmEVs) to provide a protective effect against ethanol-induced liver injury in rats. We evaluated the impact of EfmEVs on liver histological lesions, antioxidative function, alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, and serum ALT, AST, blood alcohol concentration. The results demonstrated that pretreatment with Efm significantly ameliorated ethanol-induced liver injury. Efm pretreatment mitigated the decline in ethanol-induced liver antioxidant indicators (malondialdehyde, superoxide dismutase, and glutathione peroxidase. Additionally, Efm pretreatment significantly reduced ethanol-induced ALT activities in the liver and serum, potentially by lowering blood ethanol concentration. Further, functional studies on three bioactive components (inactivated Efm, EfmEVs, and EVs-free supernatants) from the bacterial culture revealed that EVs were primarily responsible for the liver-protective effect. Moreover, EVs secretion contributed to the overall liver-protective effect of Efm. In summary, EfmEVs mediated the protective effect of Efm against ethanol-induced liver injury, potentially by improving antioxidative function and lowering blood ethanol concentration. These findings suggest that EfmEVs could serve as a potential antioxidative strategy to alleviate alcohol-induced acute liver injury.
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Affiliation(s)
- Yuanyuan Zhu
- School of Animal Science and Technology, Foshan University, Foshan, China
| | - Xiaofang Zhang
- School of Animal Science and Technology, Foshan University, Foshan, China
| | - WenHui Huang
- School of Animal Science and Technology, Foshan University, Foshan, China
| | - Meiying Luo
- School of Animal Science and Technology, Foshan University, Foshan, China
| | - Xin Feng
- School of Animal Science and Technology, Foshan University, Foshan, China
| | - Huihua Zhang
- School of Animal Science and Technology, Foshan University, Foshan, China
| | - Qien Qi
- School of Animal Science and Technology, Foshan University, Foshan, China
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3
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Fang H, Rodrigues e-Lacerda R, Barra NG, Kukje Zada D, Robin N, Mehra A, Schertzer JD. Postbiotic Impact on Host Metabolism and Immunity Provides Therapeutic Potential in Metabolic Disease. Endocr Rev 2025; 46:60-79. [PMID: 39235984 PMCID: PMC11720174 DOI: 10.1210/endrev/bnae025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 07/18/2024] [Accepted: 09/04/2024] [Indexed: 09/07/2024]
Abstract
The gut microbiota influences aspects of metabolic disease, including tissue inflammation, adiposity, blood glucose, insulin, and endocrine control of metabolism. Prebiotics or probiotics are often sought to combat metabolic disease. However, prebiotics lack specificity and can have deleterious bacterial community effects. Probiotics require live bacteria to find a colonization niche sufficient to influence host immunity or metabolism. Postbiotics encompass bacterial-derived components and molecules, which are well-positioned to alter host immunometabolism without relying on colonization efficiency or causing widespread effects on the existing microbiota. Here, we summarize the potential for beneficial and detrimental effects of specific postbiotics related to metabolic disease and the underlying mechanisms of action. Bacterial cell wall components, such as lipopolysaccharides, muropeptides, lipoteichoic acids and flagellin, have context-dependent effects on host metabolism by engaging specific immune responses. Specific types of postbiotics within broad classes of compounds, such as lipopolysaccharides and muropeptides, can have opposing effects on endocrine control of host metabolism, where certain postbiotics are insulin sensitizers and others promote insulin resistance. Bacterial metabolites, such as short-chain fatty acids, bile acids, lactate, glycerol, succinate, ethanolamine, and ethanol, can be substrates for host metabolism. Postbiotics can fuel host metabolic pathways directly or influence endocrine control of metabolism through immunomodulation or mimicking host-derived hormones. The interaction of postbiotics in the host-microbe relationship should be considered during metabolic inflammation and metabolic disease.
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Affiliation(s)
- Han Fang
- Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5
| | - Rodrigo Rodrigues e-Lacerda
- Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5
| | - Nicole G Barra
- Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5
| | - Dana Kukje Zada
- Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5
| | - Nazli Robin
- Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5
| | - Alina Mehra
- Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5
| | - Jonathan D Schertzer
- Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5
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4
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Sun X, Shukla M, Wang W, Li S. Unlocking gut-liver-brain axis communication metabolites: energy metabolism, immunity and barriers. NPJ Biofilms Microbiomes 2024; 10:136. [PMID: 39587086 PMCID: PMC11589602 DOI: 10.1038/s41522-024-00610-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 11/14/2024] [Indexed: 11/27/2024] Open
Abstract
The interaction between the gut-microbiota-derived metabolites and brain has long been recognized in both health and disease. The liver, as the primary metabolic organ for nutrients in animals or humans, plays an indispensable role in signal transduction. Therefore, in recent years, Researcher have proposed the Gut-Liver-Brain Axis (GLBA) as a supplement to the Gut-Brain Axis. The GLBA plays a crucial role in numerous physiological and pathological mechanisms through a complex interplay of signaling pathways. However, gaps remain in our knowledge regarding the developmental and functional influences of the GLBA communication pathway. The gut microbial metabolites serve as communication agents between these three distant organs, functioning prominently within the GLBA. In this review, we provide a comprehensive overview of the current understanding of the GLBA, focusing on signaling molecules role in animal and human health and disease. In this review paper elucidate its mechanisms of communication, explore its implications for immune, and energy metabolism in animal and human, and highlight future research directions. Understanding the intricate communication pathways of the GLBA holds promise for creating innovative treatment approaches for a wide range of immune and metabolic conditions.
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Affiliation(s)
- Xiaoge Sun
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, P. R. China
- Department of Neurosurgery, College of Medicine, The Pennsylvania State University, Hershey, PA, 17033, USA
| | - Manish Shukla
- Department of Neurosurgery, College of Medicine, The Pennsylvania State University, Hershey, PA, 17033, USA
| | - Wei Wang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, P. R. China.
| | - Shengli Li
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, P. R. China.
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5
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Geng X, Zhuang M, Tian W, Shang H, Gong Z, Lv Y, Li J. Green Radish Polysaccharide Prevents Alcoholic Liver Injury by Interfering with Intestinal Bacteria and Short-Chain Fatty Acids in Mice. Foods 2024; 13:3733. [PMID: 39682806 DOI: 10.3390/foods13233733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/12/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
This study aimed to ascertain the potential benefits of green radish polysaccharide (GRP) in treating alcoholic liver disease (ALD) in mice and explore its mechanism of action. Using biochemical analysis, high-throughput sequencing of gut microbiota, and gas chromatography-mass spectrometry to measure short-chain fatty acids (SCFAs) in feces, we found that GRP intervention significantly improved lipid metabolism and hepatic function in mice subjected to excessive alcohol intake. The GRP intervention reduced malondialdehyde levels by 66% and increased total superoxide dismutase levels by 22%, thereby mitigating alcohol-induced oxidative stress. Furthermore, GRP intervention in mice with alcohol consumption resulted in a reduction in tumor necrosis factor, interleukin 6, and lipopolysaccharide levels by 12%, 9%, and 25%, respectively, effectively attenuating alcoholic liver inflammation. 16S rRNA amplicon sequencing demonstrated that excessive alcohol consumption markedly altered the gut microbiota composition in mice. The GRP treatment resulted in a significant reduction in the number of beneficial bacteria (Lactobacillus and Lachnospiraceae_NK4A136_group) and an increase in the proportion of harmful bacteria (Muribaculaceae and Verrucomicrobiota). The metabolomic analyses of the SCFAs demonstrated an increase in the contents of SCFAs, acetic acid, propionic acid, and butyric acid, following GRP supplementation. Furthermore, the metabolic levels of cholinergic synapses and glycolysis/gluconeogenesis were found to be modulated. In conclusion, these findings suggest that GRP may attenuate alcohol-induced oxidative damage in the liver by modulating the gut microbiota and hepatic metabolic pathways. This may position GRP as a potential functional component for ALD prevention.
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Affiliation(s)
- Xiong Geng
- College of Food Science and Engineering, Bohai University, Jinzhou 121013, China
| | - Miaomiao Zhuang
- College of Food Science and Engineering, Bohai University, Jinzhou 121013, China
| | - Weina Tian
- College of Food Science and Engineering, Bohai University, Jinzhou 121013, China
| | - Huayan Shang
- College of Food Science and Engineering, Bohai University, Jinzhou 121013, China
| | - Ziyi Gong
- College of Food Science and Engineering, Bohai University, Jinzhou 121013, China
| | - Yanfang Lv
- College of Food Science and Engineering, Bohai University, Jinzhou 121013, China
| | - Jianrong Li
- College of Food Science and Engineering, Bohai University, Jinzhou 121013, China
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6
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Domínguez-Pino M, Mellado S, Cuesta CM, Grillo-Risco R, García-García F, Pascual M. Metagenomics Reveals Sex-Based Differences in Murine Fecal Microbiota Profiles Induced by Chronic Alcohol Consumption. Int J Mol Sci 2024; 25:12534. [PMID: 39684246 DOI: 10.3390/ijms252312534] [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: 10/10/2024] [Revised: 11/19/2024] [Accepted: 11/20/2024] [Indexed: 12/18/2024] Open
Abstract
Chronic ethanol exposure induces an inflammatory response within the intestinal tract, compromising mucosal and epithelial integrity and leading to dysbiosis of the gut microbiome. However, the specific roles of the gut microbiota in mediating ethanol-induced effects, as well as their interactions with the immune system, remain poorly characterized. This study aimed to evaluate sex-based differences in fecal microbiota profiles induced by chronic alcohol consumption and to assess whether TLR4 is involved in these effects. We analyzed the 16S rRNA gene sequencing of fecal samples from male and female wild-type (WT) and TLR4-knockout (TLR4-KO) mice with and without chronic ethanol exposure over a three-month period. Our findings provide evidence, for the first time, that male mice are more susceptible to the effects of ethanol on the fecal microbiota, since ethanol exposure induced greater alterations in the Gram-negative and -positive bacteria with immunogenic capacity in the WT male mice than in the female mice. We also demonstrate that the absence of immune receptor TLR4 leads to different microbiota in both sexes, showing anti-inflammatory and protective properties for intestinal barrier function and resulting in a phenotype more resistant to ethanol's effects. These findings may open new avenues for understanding the relationship between gut microbiota profiles and inflammation in the digestive system induced by chronic alcohol consumption.
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Affiliation(s)
- Manuel Domínguez-Pino
- Computational Biomedicine Laboratory, Príncipe Felipe Research Center, C/Eduardo Primo Yúfera, 3, 46012 Valencia, Spain
| | - Susana Mellado
- Department of Physiology, School of Medicine and Dentistry, University of Valencia, Avda. Blasco Ibáñez, 15, 46010 Valencia, Spain
| | - Carlos M Cuesta
- Department of Physiology, School of Medicine and Dentistry, University of Valencia, Avda. Blasco Ibáñez, 15, 46010 Valencia, Spain
| | - Rubén Grillo-Risco
- Computational Biomedicine Laboratory, Príncipe Felipe Research Center, C/Eduardo Primo Yúfera, 3, 46012 Valencia, Spain
| | - Francisco García-García
- Computational Biomedicine Laboratory, Príncipe Felipe Research Center, C/Eduardo Primo Yúfera, 3, 46012 Valencia, Spain
| | - María Pascual
- Department of Physiology, School of Medicine and Dentistry, University of Valencia, Avda. Blasco Ibáñez, 15, 46010 Valencia, Spain
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7
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Yan M, Man S, Ma L, Guo L, Huang L, Gao W. Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives. Clin Mol Hepatol 2024; 30:620-648. [PMID: 38988278 PMCID: PMC11540396 DOI: 10.3350/cmh.2024.0315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 07/10/2024] [Accepted: 07/10/2024] [Indexed: 07/12/2024] Open
Abstract
Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Understanding the immunological mechanisms underlying SLD is crucial for advancing clinical therapeutic strategies.
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Affiliation(s)
- Mengyao Yan
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China
| | - Shuli Man
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China
| | - Long Ma
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China
| | - Lanping Guo
- National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Luqi Huang
- National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wenyuan Gao
- Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin, China
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8
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Bharti A, Sharma I, Mahajan R, Langer S, Kapoor N. From Cirrhosis to the Dysbiosis (A Loop of Cure or Complications?). Indian J Microbiol 2024; 64:810-820. [PMID: 39282182 PMCID: PMC11399373 DOI: 10.1007/s12088-024-01267-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 03/18/2024] [Indexed: 09/18/2024] Open
Abstract
Gut dysbiosis and liver cirrhosis are two corelated complications that highly disturbs the metabolism of a normal human body. Liver cirrhosis is scarring of the hepatic tissue and gut dysbiosis is the imbalance in the microbiome of the gut. Gut dysbiosis in cirrhosis occurs due to increased permeability of the intestinal membrane which might induce immune responses and damage the normal functioning of the body. Dysbiosis can cause liver damage from cirrhosis and can further lead to liver failure by hepatocellular carcinoma. In this review we discuss if eubiosis can revert the poorly functioning cirrhotic liver to normal functioning state? A normal microbiome converts various liver products into usable forms that regulates the overgrowth of microbiome in the gut. The imbalance caused by dysbiosis retards the normal functioning of liver and increases the complications. To correct this dysbiosis, measures like use of antibiotics with probiotics and prebiotics are used. This correction of the gut microbiome serves as a ray of hope to recover from this chronic illness. In case of alcohol induced liver cirrhosis, intervention of microbes can possibly be helpful in modulating the addiction as well as associated complications like depression as microbes are known to produce and consume neurotransmitters that are involved in alcohol addiction. Hence a correction of gut liver brain axis using microbiome can be a milestone achieved not only for treatment of liver cirrhosis but also for helping alcohol addicts quit and live a healthy or at least a near healthy life.
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Affiliation(s)
- Aanchal Bharti
- School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir 180006 India
| | - Isar Sharma
- School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir 180006 India
| | - Ritu Mahajan
- School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir 180006 India
| | - Seema Langer
- Department of Zoology, University of Jammu, Jammu, Jammu and Kashmir 180006 India
| | - Nisha Kapoor
- School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir 180006 India
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9
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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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10
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Jiang M, Zheng Z, Wang X, Chen Y, Qu J, Ding Q, Zhang W, Liu YS, Yang J, Tang W, Hou Y, He J, Wang L, Huang P, Li LC, He Z, Gao Q, Lu Q, Wei L, Wang YJ, Ju Z, Fan JG, Ruan XZ, Guan Y, Liu GH, Pei G, Li J, Wang Y. A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement. LIFE MEDICINE 2024; 3:lnae004. [PMID: 39872390 PMCID: PMC11749002 DOI: 10.1093/lifemedi/lnae004] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 01/29/2024] [Indexed: 01/11/2025]
Abstract
In human aging, liver aging per se not only increases susceptibility to liver diseases but also increases vulnerability of other organs given its central role in regulating metabolism. Total liver function tends to be well maintained in the healthy elderly, so liver aging is generally difficult to identify early. In response to this critical challenge, the Aging Biomarker Consortium of China has formulated an expert consensus on biomarkers of liver aging by synthesizing the latest scientific literature, comprising insights from both scientists and clinicians. This consensus provides a comprehensive assessment of biomarkers associated with liver aging and presents a systematic framework to characterize these into three dimensions: functional, imaging, and humoral. For the functional domain, we highlight biomarkers associated with cholesterol metabolism and liver-related coagulation function. For the imaging domain, we note that hepatic steatosis and liver blood flow can serve as measurable biomarkers for liver aging. Finally, in the humoral domain, we pinpoint hepatokines and enzymatic alterations worthy of attention. The aim of this expert consensus is to establish a foundation for assessing the extent of liver aging and identify early signs of liver aging-related diseases, thereby improving liver health and the healthy life expectancy of the elderly population.
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Affiliation(s)
| | - Mengmeng Jiang
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
| | - Zhuozhao Zheng
- Department of Radiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Xuan Wang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Yanhao Chen
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
| | - Jing Qu
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
| | - Qiurong Ding
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
| | - Weiqi Zhang
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China
| | - You-Shuo Liu
- Department of Geriatrics, the Second Xiangya Hospital, and the Institute of Aging and Geriatrics, Central South University, Changsha 410011, China
| | - Jichun Yang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Center for Non-coding RNA Medicine, Peking University Health Science Center, Beijing 100191, China
| | - Weiqing Tang
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China
| | - Yunlong Hou
- Yiling Pharmaceutical Academician Workstation, Shijiazhuang 050035, China
| | - Jinhan He
- Department of Pharmacy, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Lin Wang
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
| | - Pengyu Huang
- State Key Laboratory of Advanced Medical Materials and Devices, Engineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China
| | - Lin-Chen Li
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, China
| | - Zhiying He
- Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai Engineering Research Center of Stem Cells Translational Medicine, Shanghai 200092, China
| | - Qiang Gao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Qian Lu
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
- Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Yan-Jiang Wang
- Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China
| | - Zhenyu Ju
- Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou 510632, China
| | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Xiong Zhong Ruan
- Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China
| | - Youfei Guan
- Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China
| | - Guang-Hui Liu
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Gang Pei
- Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai 200092, China
| | - Jian Li
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China
| | - Yunfang Wang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
- Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, China
- Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), School of Clinical Medicine, Tsinghua University, Beijing 102218, China
- Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing 102218, China
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11
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Zhou M, Li X, Wang X, Deng N, Cai Y, Tan Z. The dysfunction in intestinal microorganisms and enzyme activity as significant contributors to diarrhea with kidney-yang deficiency syndrome. Front Microbiol 2024; 14:1324938. [PMID: 38264481 PMCID: PMC10803573 DOI: 10.3389/fmicb.2023.1324938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 12/19/2023] [Indexed: 01/25/2024] Open
Abstract
OBJECT To investigate the pathogenesis of diarrhea with kidney-yang deficiency syndrome by examining characteristic changes in intestinal microorganisms, enzyme activities, oxidative stress, and metabolism indices. METHODS Twenty mice were randomly and equally divided into control group (NC) and model group (NM). Mice in NM group received adenine suspension at a dosage of 50 mg/(kg⋅day) by gavage, 0.4 mL/time, once a day for 14 days, and Folium sennae decoction at a dosage of 10 g/(kg⋅day) by gavage, 0.4 mL/time, once a day for 7 days, starting on 8th day. Mice in NC group were administered an equivalent amount of sterile water by gavage once a day for 7 days, and twice a day from the 8th day. After modeling, assessments encompassed microbial culture, organ index calculation, microbial and enzyme activity detection, malondialdehyde (MDA) content determination, superoxide dismutase (SOD) activity, blood biochemical tests, and observation of kidney tissue pathological changes. RESULTS The results showed that in NM group, a reduction in the number of Lactobacillus and Bifidobacteria was noted, accompanied by an increase in the number of bacteria and E. coli. Xylanase activity in the intestinal contents and mucosa, protease activity in the intestinal mucosa, and intestinal mucosa microbial activity were diminished. Conversely, the activities of amylase, sucrase, and lactase increased in intestinal mucosa. Additionally, there was an elevation in the level of MDA. Renal tubular dilatation and inflammatory cell infiltration were observed in the renal interstitium. CONCLUSION These dysfunctions in intestinal microorganisms and enzyme activities suggest potential involvement in diarrhea with kidney-yang deficiency syndrome.
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Affiliation(s)
- Mengsi Zhou
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Xiaoya Li
- Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Kunming, Yunnan University of Traditional Chinese Medicine, Kunming, Yunan, China
| | - Xuehong Wang
- The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Na Deng
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Ying Cai
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Zhoujin Tan
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
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12
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Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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LeFort KR, Rungratanawanich W, Song BJ. Melatonin Prevents Alcohol- and Metabolic Dysfunction- Associated Steatotic Liver Disease by Mitigating Gut Dysbiosis, Intestinal Barrier Dysfunction, and Endotoxemia. Antioxidants (Basel) 2023; 13:43. [PMID: 38247468 PMCID: PMC10812487 DOI: 10.3390/antiox13010043] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/19/2023] [Accepted: 12/22/2023] [Indexed: 01/23/2024] Open
Abstract
Melatonin (MT) has often been used to support good sleep quality, especially during the COVID-19 pandemic, as many have suffered from stress-related disrupted sleep patterns. It is less known that MT is an antioxidant, anti-inflammatory compound, and modulator of gut barrier dysfunction, which plays a significant role in many disease states. Furthermore, MT is produced at 400-500 times greater concentrations in intestinal enterochromaffin cells, supporting the role of MT in maintaining the functions of the intestines and gut-organ axes. Given this information, the focus of this article is to review the functions of MT and the molecular mechanisms by which it prevents alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), including its metabolism and interactions with mitochondria to exert its antioxidant and anti-inflammatory activities in the gut-liver axis. We detail various mechanisms by which MT acts as an antioxidant, anti-inflammatory compound, and modulator of intestinal barrier function to prevent the progression of ALD and MASLD via the gut-liver axis, with a focus on how these conditions are modeled in animal studies. Using the mechanisms of MT prevention and animal studies described, we suggest behavioral modifications and several exogenous sources of MT, including food and supplements. Further clinical research should be performed to develop the field of MT in preventing the progression of liver diseases via the gut-liver axis, so we mention a few considerations regarding MT supplementation in the context of clinical trials in order to advance this field of research.
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Affiliation(s)
- Karli R. LeFort
- Section of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, 9000 Rockville Pike, Bethesda, MD 20892, USA;
| | | | - Byoung-Joon Song
- Section of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, 9000 Rockville Pike, Bethesda, MD 20892, USA;
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14
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Xu F, Chen Z, Xie L, Yang S, Li Y, Wu J, Wu Y, Li S, Zhang X, Ma Y, Liu Y, Zeng A, Xu Z. Lactobacillus plantarum ST-III culture supernatant protects against acute alcohol-induced liver and intestinal injury. Aging (Albany NY) 2023; 16:2077-2089. [PMID: 38126998 PMCID: PMC10911357 DOI: 10.18632/aging.205331] [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: 07/18/2023] [Accepted: 11/06/2023] [Indexed: 12/23/2023]
Abstract
The beneficial effects of probiotics have been studied in inflammatory bowel disease, nonalcoholic steatohepatitis, and alcoholic liver disease (ALD). Probiotic supplements are safer and more effective; however, their potential mechanisms are unclear. An objective of the current study was to examine the effects of extracellular products of Lactobacillus plantarum on acute alcoholic liver injury. Mice on a standard chow diet were supplemented with Lactobacillus plantarum ST-III culture supernatant (LP-cs) for two weeks and administered alcohol at 6 g/kg body weight by gavage. Alcohol-induced liver injury was assessed by measuring plasma alanine aminotransferase activity levels and triglyceride content determined liver steatosis. Intestinal damage and tight junctions were assessed using histochemical staining. LP-cs significantly inhibited alcohol-induced fat accumulation, inflammation, and apoptosis by inhibiting oxidative stress and endoplasmic reticulum stress. LP-cs significantly inhibited alcohol-induced intestinal injury and endotoxemia. These findings suggest that LP-cs alleviates acute alcohol-induced liver damage by inhibiting oxidative stress and endoplasmic reticulum stress via one mechanism and suppressing alcohol-induced increased intestinal permeability and endotoxemia via another mechanism. LP-cs supplements are a novel strategy for ALD prevention and treatment.
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Affiliation(s)
- Feng Xu
- Department of Gastroenterology, Ningbo Medical Center Li Huili Hospital, The Affiliated Hospital of Ningbo University, Ningbo 315000, China
| | - Zengqiang Chen
- Healthcare Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Longteng Xie
- Department of Infection Diseases, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo 315700, China
| | - Shizhuo Yang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China
| | - Yuying Li
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China
- Ruian People's Hospital, Wenzhou Medical College Affiliated Third Hospital, Wenzhou 325200, China
| | - Junnan Wu
- School of Mental Health, Wenzhou Medical University, Wenzhou 325035, China
| | - Yuyu Wu
- School of Mental Health, Wenzhou Medical University, Wenzhou 325035, China
| | - Siyuan Li
- School of Mental Health, Wenzhou Medical University, Wenzhou 325035, China
| | - Xie Zhang
- Department of Pharmacy, Ningbo Medical Center Li Huili Hospital, The Affiliated Hospital of Ningbo University, Ningbo 315000, China
| | - Yanyan Ma
- Department of Gastroenterology, Ningbo Medical Center Li Huili Hospital, The Affiliated Hospital of Ningbo University, Ningbo 315000, China
| | - Yanlong Liu
- School of Mental Health, Wenzhou Medical University, Wenzhou 325035, China
| | - Aibing Zeng
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China
| | - Zeping Xu
- Department of Pharmacy, Ningbo Medical Center Li Huili Hospital, The Affiliated Hospital of Ningbo University, Ningbo 315000, China
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15
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Cartus AT, Lachenmeier DW, Guth S, Roth A, Baum M, Diel P, Eisenbrand G, Engeli B, Hellwig M, Humpf HU, Joost HG, Kulling SE, Lampen A, Marko D, Steinberg P, Wätjen W, Hengstler JG, Mally A. Acetaldehyde as a Food Flavoring Substance: Aspects of Risk Assessment. Mol Nutr Food Res 2023; 67:e2200661. [PMID: 37840378 DOI: 10.1002/mnfr.202200661] [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: 09/28/2022] [Revised: 05/31/2023] [Indexed: 10/17/2023]
Abstract
The Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) has reviewed the currently available data in order to assess the health risks associated with the use of acetaldehyde as a flavoring substance in foods. Acetaldehyde is genotoxic in vitro. Following oral intake of ethanol or inhalation exposure to acetaldehyde, systemic genotoxic effects of acetaldehyde in vivo cannot be ruled out (induction of DNA adducts and micronuclei). At present, the key question of whether acetaldehyde is genotoxic and mutagenic in vivo after oral exposure cannot be answered conclusively. There is also insufficient data on human exposure. Consequently, it is currently not possible to reliably assess the health risk associated with the use of acetaldehyde as a flavoring substance. However, considering the genotoxic potential of acetaldehyde as well as numerous data gaps that need to be filled to allow a comprehensive risk assessment, the SKLM considers that the use of acetaldehyde as a flavoring may pose a safety concern. For reasons of precautionary consumer protection, the SKLM recommends that the scientific base for approval of the intentional addition of acetaldehyde to foods as a flavoring substance should be reassessed.
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Affiliation(s)
| | - Dirk W Lachenmeier
- Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weißenburger Str. 3, 76187, Karlsruhe, Germany
| | - Sabine Guth
- Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystr, 67, 44139, Dortmund, Germany
| | - Angelika Roth
- Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystr, 67, 44139, Dortmund, Germany
| | - Matthias Baum
- Solenis Germany Industries GmbH, Fütingsweg 20, 47805, Krefeld, Germany
| | - Patrick Diel
- Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany
| | | | - Barbara Engeli
- Federal Food Safety and Veterinary Office (FSVO), Risk Assessment Division, Schwarzenburgstrasse 155, Bern, 3003, Switzerland
| | - Michael Hellwig
- Chair of Special Food Chemistry, Technische Universität Dresden, Bergstraße 66, 01062, Dresden, Germany
| | - Hans-Ulrich Humpf
- Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstraße 45, 48149, Münster, Germany
| | - Hans-Georg Joost
- Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany
| | - Sabine E Kulling
- Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Straße 9, 76131, Karlsruhe, Germany
| | - Alfonso Lampen
- Risk Assessment Strategies, Bundesinstitut für Risikobewertung (BfR), Max-Dohrn-Straße 8-10, Berlin, Germany
| | - Doris Marko
- Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Straße 38, Vienna, 1090, Austria
| | - Pablo Steinberg
- Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Str. 9, 76131, Karlsruhe, Germany
| | - Wim Wätjen
- Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany
| | - Jan G Hengstler
- Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystr, 67, 44139, Dortmund, Germany
| | - Angela Mally
- Department of Toxicology, University of Würzburg, Versbacher Str. 9, 97078, Würzburg, Germany
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16
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Krishnamurthy HK, Pereira M, Bosco J, George J, Jayaraman V, Krishna K, Wang T, Bei K, Rajasekaran JJ. Gut commensals and their metabolites in health and disease. Front Microbiol 2023; 14:1244293. [PMID: 38029089 PMCID: PMC10666787 DOI: 10.3389/fmicb.2023.1244293] [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: 06/22/2023] [Accepted: 10/16/2023] [Indexed: 12/01/2023] Open
Abstract
Purpose of review This review comprehensively discusses the role of the gut microbiome and its metabolites in health and disease and sheds light on the importance of a holistic approach in assessing the gut. Recent findings The gut microbiome consisting of the bacteriome, mycobiome, archaeome, and virome has a profound effect on human health. Gut dysbiosis which is characterized by perturbations in the microbial population not only results in gastrointestinal (GI) symptoms or conditions but can also give rise to extra-GI manifestations. Gut microorganisms also produce metabolites (short-chain fatty acids, trimethylamine, hydrogen sulfide, methane, and so on) that are important for several interkingdom microbial interactions and functions. They also participate in various host metabolic processes. An alteration in the microbial species can affect their respective metabolite concentrations which can have serious health implications. Effective assessment of the gut microbiome and its metabolites is crucial as it can provide insights into one's overall health. Summary Emerging evidence highlights the role of the gut microbiome and its metabolites in health and disease. As it is implicated in GI as well as extra-GI symptoms, the gut microbiome plays a crucial role in the overall well-being of the host. Effective assessment of the gut microbiome may provide insights into one's health status leading to more holistic care.
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Affiliation(s)
| | | | - Jophi Bosco
- Vibrant America LLC., San Carlos, CA, United States
| | | | | | | | - Tianhao Wang
- Vibrant Sciences LLC., San Carlos, CA, United States
| | - Kang Bei
- Vibrant Sciences LLC., San Carlos, CA, United States
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17
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Wang M, Jiang Y, Wang S, Fu L, Liang Z, Zhang Y, Huang X, Li X, Feng M, Long D. Yak milk protects against alcohol-induced liver injury in rats. Food Funct 2023; 14:9857-9871. [PMID: 37853817 DOI: 10.1039/d3fo03675h] [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: 10/20/2023]
Abstract
The protective effects of yak milk (YM) against chronic alcoholic liver injury in rats were investigated in this study. Histologic and biochemical analyses demonstrated that YM consumption ameliorates alcohol-induced liver injury by increasing the liver antioxidant enzyme activity and reducing inflammation. Furthermore, microbiome and metabolomic analyses exploring YM's impact on gut microbiota and metabolism found that YM administration regulates gut microbiota composition. Specifically, there was a decrease in the relative abundance of Helicobacter, Streptococcus, Peptococcus and Tyzzerella, along with an increase in Turisibacter and Intestinimonas. Moreover, Pearson analysis indicated positive correlations between Peptococcus and Tyzzerella with ALT and AST levels, while showing a negative correlation with ADH levels. Furthermore, differential metabolite analysis of fecal samples from the YM group identified significant increases in the taurine (2-Aminoethanesulfonic acid), hypotaurine (2-Aminoethanesulfonic Acid) and isethionic acid levels. Finally, KEGG topology analysis highlighted taurine and hypotaurine metabolism as the primary pathways influenced by YM intervention. Therefore, these findings collectively suggest that YM may protect alcohol-exposed rats against liver injury by modulating oxidative stress, inflammatory response, gut microbiota disorder, and metabolic regulation.
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Affiliation(s)
- Man Wang
- School of Public Health, Lanzhou University, Lanzhou, China.
| | - Yanshi Jiang
- School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, China
| | - Siying Wang
- School of Public Health, Lanzhou University, Lanzhou, China.
| | - Lin Fu
- School of Public Health, Lanzhou University, Lanzhou, China.
| | - Zujin Liang
- School of Public Health, Lanzhou University, Lanzhou, China.
| | - Ying Zhang
- School of Public Health, Lanzhou University, Lanzhou, China.
| | - Xiaodan Huang
- School of Public Health, Lanzhou University, Lanzhou, China.
| | - Xin Li
- School of Public Health, Lanzhou University, Lanzhou, China.
| | - Meiying Feng
- School of Public Health, Lanzhou University, Lanzhou, China.
| | - Danfeng Long
- School of Public Health, Lanzhou University, Lanzhou, China.
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18
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Aghara H, Chadha P, Zala D, Mandal P. Stress mechanism involved in the progression of alcoholic liver disease and the therapeutic efficacy of nanoparticles. Front Immunol 2023; 14:1205821. [PMID: 37841267 PMCID: PMC10570533 DOI: 10.3389/fimmu.2023.1205821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 09/07/2023] [Indexed: 10/17/2023] Open
Abstract
Alcoholic liver disease (ALD) poses a significant threat to human health, with excessive alcohol intake disrupting the immunotolerant environment of the liver and initiating a cascade of pathological events. This progressive disease unfolds through fat deposition, proinflammatory cytokine upregulation, activation of hepatic stellate cells, and eventual development of end-stage liver disease, known as hepatocellular carcinoma (HCC). ALD is intricately intertwined with stress mechanisms such as oxidative stress mediated by reactive oxygen species, endoplasmic reticulum stress, and alcohol-induced gut dysbiosis, culminating in increased inflammation. While the initial stages of ALD can be reversible with diligent care and abstinence, further progression necessitates alternative treatment approaches. Herbal medicines have shown promise, albeit limited by their poor water solubility and subsequent lack of extensive exploration. Consequently, researchers have embarked on a quest to overcome these challenges by delving into the potential of nanoparticle-mediated therapy. Nanoparticle-based treatments are being explored for liver diseases that share similar mechanisms with alcoholic liver disease. It underscores the potential of these innovative approaches to counteract the complex pathogenesis of ALD, providing new avenues for therapeutic intervention. Nevertheless, further investigations are imperative to fully unravel the therapeutic potential and unlock the promise of nanoparticle-mediated therapy specifically tailored for ALD treatment.
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Affiliation(s)
| | | | | | - Palash Mandal
- P D Patel Institute of Applied Sciences, Charotar University of Science and Technology, Anand, Gujarat, India
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19
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Aghara H, Chadha P, Zala D, Mandal P. Stress mechanism involved in the progression of alcoholic liver disease and the therapeutic efficacy of nanoparticles. Front Immunol 2023; 14. [DOI: https:/doi.org/10.3389/fimmu.2023.1205821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023] Open
Abstract
Alcoholic liver disease (ALD) poses a significant threat to human health, with excessive alcohol intake disrupting the immunotolerant environment of the liver and initiating a cascade of pathological events. This progressive disease unfolds through fat deposition, proinflammatory cytokine upregulation, activation of hepatic stellate cells, and eventual development of end-stage liver disease, known as hepatocellular carcinoma (HCC). ALD is intricately intertwined with stress mechanisms such as oxidative stress mediated by reactive oxygen species, endoplasmic reticulum stress, and alcohol-induced gut dysbiosis, culminating in increased inflammation. While the initial stages of ALD can be reversible with diligent care and abstinence, further progression necessitates alternative treatment approaches. Herbal medicines have shown promise, albeit limited by their poor water solubility and subsequent lack of extensive exploration. Consequently, researchers have embarked on a quest to overcome these challenges by delving into the potential of nanoparticle-mediated therapy. Nanoparticle-based treatments are being explored for liver diseases that share similar mechanisms with alcoholic liver disease. It underscores the potential of these innovative approaches to counteract the complex pathogenesis of ALD, providing new avenues for therapeutic intervention. Nevertheless, further investigations are imperative to fully unravel the therapeutic potential and unlock the promise of nanoparticle-mediated therapy specifically tailored for ALD treatment.
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20
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Fang Q, Yu L, Tian F, Zhang H, Chen W, Zhai Q. Effects of dietary irritants on intestinal homeostasis and the intervention strategies. Food Chem 2023; 409:135280. [PMID: 36587512 DOI: 10.1016/j.foodchem.2022.135280] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 12/11/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022]
Abstract
Abundant diet components are unexplored as vital factors in intestinal homeostasis. Dietary irritants stimulate the nervous system and provoke somatosensory responses, further inducing diarrhea, gut microbiota disorder, intestinal barrier damage or even severe gastrointestinal disease. We depicted the effects of food with piquancy, high fat, low pH, high-refined carbohydrates, and indigestible texture. The mechanism of dietary irritants on intestinal homeostasis were comprehensively summarized. Somatosensory responses to dietary irritants are palpable and have specific chemical and neural mechanisms. In contrast, even low-dose exposure to dietary irritants can involve multiple intestinal barriers. Their mechanisms in intestinal homeostasis are often overlapping and dose-dependent. Therefore, treating symptoms caused by dietary irritants requires personalized nutritional advice. The reprocessing of stimulant foods, additional supplementation with probiotics or prebiotics, and enhancement of the intestinal barrier are effective intervention strategies. This review provides promising preliminary guidelines for the treatment of symptoms and gastrointestinal injury caused by dietary irritants.
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Affiliation(s)
- Qingying Fang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China
| | - Leilei Yu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China
| | - Fengwei Tian
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China; Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, PR China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, PR China; Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute, Wuxi Branch, PR China; Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, PR China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, PR China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, PR China; Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, PR China.
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21
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Lutein Prevents Liver Injury and Intestinal Barrier Dysfunction in Rats Subjected to Chronic Alcohol Intake. Nutrients 2023; 15:nu15051229. [PMID: 36904226 PMCID: PMC10005241 DOI: 10.3390/nu15051229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/22/2023] [Accepted: 02/24/2023] [Indexed: 03/05/2023] Open
Abstract
Chronic alcohol intake can affect both liver and intestinal barrier function. The goal of this investigation was to evaluate the function and mechanism of lutein administration on the chronic ethanol-induced liver and intestinal barrier damage in rats. During the 14-week experimental cycle, seventy rats were randomly divided into seven groups, with 10 rats in each group: a normal control group (Co), a control group of lutein interventions (24 mg/kg/day), an ethanol model group (Et, 8-12 mL/kg/day of 56% (v/v) ethanol), three intervention groups with lutein (12, 24 and 48 mg/kg/day) and a positive control group (DG). The results showed that liver index, ALT, AST and TG levels were increased, and SOD and GSH-Px levels were reduced in the Et group. Furthermore, alcohol intake over a long time increased the level of pro-inflammatory cytokines TNF-α and IL-1β, disrupted the intestinal barrier, and stimulated the release of LPS, causing further liver injury. In contrast, lutein interventions prevented alcohol-induced alterations in liver tissue, oxidative stress and inflammation. In addition, the protein expression of Claudin-1 and Occludin in ileal tissues was upregulated by lutein intervention. In conclusion, lutein can improve chronic alcoholic liver injury and intestinal barrier dysfunction in rats.
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22
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Ye W, Chen Z, He Z, Gong H, Zhang J, Sun J, Yuan S, Deng J, Liu Y, Zeng A. Lactobacillus plantarum-Derived Postbiotics Ameliorate Acute Alcohol-Induced Liver Injury by Protecting Cells from Oxidative Damage, Improving Lipid Metabolism, and Regulating Intestinal Microbiota. Nutrients 2023; 15:nu15040845. [PMID: 36839205 PMCID: PMC9965849 DOI: 10.3390/nu15040845] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 01/19/2023] [Accepted: 01/30/2023] [Indexed: 02/10/2023] Open
Abstract
Here, the aim was to evaluate the protective effect of Lactobacillus plantarum-derived postbiotics, i.e., LP-cs, on acute alcoholic liver injury (ALI). After preincubation with LP-cs, HL7702 human hepatocytes were treated with alcohol, and then the cell survival rate was measured. C57BL/6 male mice were presupplemented with or without LP-cs and LP-cs-loaded calcium alginate hydrogel (LP-cs-Gel) for 3 weeks and given 50% alcohol gavage to establish the mouse model of ALI, LP-cs presupplementation, and LP-cs-Gel presupplementation. The histomorphology of the liver and intestines; the levels of serum AST, ALT, lipid, and SOD activity; liver transcriptomics; and the metagenome of intestinal microbiota were detected in all mouse models. In vitro, LP-cs significantly increased the survival rate of alcohol-treated cells. In vivo, presupplementation with LP-cs and LP-cs-Gel restored the levels of serum AST, ALT, and SOD activity, as well as TC and TG, after acute alcohol intake. In the LP-cs-presupplemented mice, the genes involved in fatty acid metabolic processes were upregulated and the genes involved in steroid biosynthesis were downregulated significantly as compared with the ALI mice. LP-cs significantly increased the abundance of intestinal microbiota, especially Akkermansia muciniphila. In conclusion, LP-cs ameliorates ALI by protecting hepatocytes against oxidative damage, thereby, improving lipid metabolism and regulating the intestinal microbiota. The effect of LP-cs-Gel is similar to that of LP-cs.
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Affiliation(s)
- Wei Ye
- School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China
| | - Zengqiang Chen
- Healthcare Center of the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Zhuoqi He
- School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China
| | - Haochen Gong
- School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China
| | - Jin Zhang
- School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China
| | - Jiaju Sun
- School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China
| | - Shanshan Yuan
- Wenzhou Institute, University of Chinese Academy Sciences, Wenzhou 325000, China
| | - Junjie Deng
- Wenzhou Institute, University of Chinese Academy Sciences, Wenzhou 325000, China
| | - Yanlong Liu
- School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325035, China
| | - Aibing Zeng
- School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China
- Correspondence:
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23
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Cárdenas-Escudero J, Mármol-Rojas C, Escribano Pintor S, Galán-Madruga D, Cáceres JO. Honey polyphenols: regulators of human microbiota and health. Food Funct 2023; 14:602-620. [PMID: 36541681 DOI: 10.1039/d2fo02715a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
A comprehensive review of research over the last decade was conducted to carry out this work. The main objective of this work is to present relevant evidence of the effect of honey intake on the human intestinal microbiota and its relationship with the improvement of various chronic diseases, such as cirrhosis, metabolic syndrome, diabetes, and obesity, among others. Therefore, this work focuses on the health-improving honey dietary supplementation implications associated with specific changes in the human microbiota and their biochemical mechanisms to enhance the proliferation of beneficial microorganisms and the inhibition of pathogenic microorganisms. Consumption of honey polyphenols significantly improves people's health conditions, especially in patients with chronic disease. Hence, honey intake unequivocally constitutes an alternative way to enhance health and could be used to prevent some relevant chronic diseases.
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Affiliation(s)
- J Cárdenas-Escudero
- Laser Chemistry Research Group, Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, Plaza de Ciencias 1, 28040 Madrid, Spain. .,Analytical Chemistry Department, FCNET, Universidad de Panamá, Bella Vista, Manuel E. Batista and José De Fábrega av., Ciudad Universitaria, Estafeta Universitaria, 3366, Panamá 4, Panamá
| | - C Mármol-Rojas
- Laser Chemistry Research Group, Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, Plaza de Ciencias 1, 28040 Madrid, Spain.
| | - S Escribano Pintor
- Laser Chemistry Research Group, Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, Plaza de Ciencias 1, 28040 Madrid, Spain.
| | - D Galán-Madruga
- National Centre for Environmental Health. Carlos III Health Institute, Ctra. Majadahonda-Pozuelo km 2.2, 28220 Majadahonda, Madrid, Spain
| | - J O Cáceres
- Laser Chemistry Research Group, Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, Plaza de Ciencias 1, 28040 Madrid, Spain.
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Xu Z, Jiang N, Xiao Y, Yuan K, Wang Z. The role of gut microbiota in liver regeneration. Front Immunol 2022; 13:1003376. [PMID: 36389782 PMCID: PMC9647006 DOI: 10.3389/fimmu.2022.1003376] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 10/12/2022] [Indexed: 12/02/2022] Open
Abstract
The liver has unique regeneration potential, which ensures the continuous dependence of the human body on hepatic functions. As the composition and function of gut microbiota has been gradually elucidated, the vital role of gut microbiota in liver regeneration through gut-liver axis has recently been accepted. In the process of liver regeneration, gut microbiota composition is changed. Moreover, gut microbiota can contribute to the regulation of the liver immune microenvironment, thereby modulating the release of inflammatory factors including IL-6, TNF-α, HGF, IFN-γ and TGF-β, which involve in different phases of liver regeneration. And previous research have demonstrated that through enterohepatic circulation, bile acids (BAs), lipopolysaccharide, short-chain fatty acids and other metabolites of gut microbiota associate with liver and may promote liver regeneration through various pathways. In this perspective, by summarizing gut microbiota-derived signaling pathways that promote liver regeneration, we unveil the role of gut microbiota in liver regeneration and provide feasible strategies to promote liver regeneration by altering gut microbiota composition.
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Affiliation(s)
- Zhe Xu
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Nan Jiang
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yuanyuan Xiao
- Department of Obstetrics and Gynecology, West China Second Hospital of Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
- *Correspondence: Zhen Wang, ; Kefei Yuan, ; Yuanyuan Xiao,
| | - Kefei Yuan
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- *Correspondence: Zhen Wang, ; Kefei Yuan, ; Yuanyuan Xiao,
| | - Zhen Wang
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- *Correspondence: Zhen Wang, ; Kefei Yuan, ; Yuanyuan Xiao,
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Role of Intestinal Microbes in Chronic Liver Diseases. Int J Mol Sci 2022; 23:ijms232012661. [PMID: 36293518 PMCID: PMC9603943 DOI: 10.3390/ijms232012661] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/15/2022] [Accepted: 10/19/2022] [Indexed: 11/07/2022] Open
Abstract
With the recent availability and upgrading of many emerging intestinal microbes sequencing technologies, our research on intestinal microbes is changing rapidly. A variety of investigations have found that intestinal microbes are essential for immune system regulation and energy metabolism homeostasis, which impacts many critical organs. The liver is the first organ to be traversed by the intestinal portal vein, and there is a strong bidirectional link between the liver and intestine. Many intestinal factors, such as intestinal microbes, bacterial composition, and intestinal bacterial metabolites, are deeply involved in liver homeostasis. Intestinal microbial dysbiosis and increased intestinal permeability are associated with the pathogenesis of many chronic liver diseases, such as alcoholic fatty liver disease (AFLD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), chronic hepatitis B (CHB), chronic hepatitis C (CHC), autoimmune liver disease (AIH) and the development of hepatocellular carcinoma (HCC). Intestinal permeability and dysbacteriosis often lead to Lipopolysaccharide (LPS) and metabolites entering in serum. Then, Toll-like receptors activation in the liver induces the exposure of the intestine and liver to many small molecules with pro-inflammatory properties. And all of these eventually result in various liver diseases. In this paper, we have discussed the current evidence on the role of various intestinal microbes in different chronic liver diseases. As well as potential new therapeutic approaches are proposed in this review, such as antibiotics, probiotics, and prebiotics, which may have an improvement in liver diseases.
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Sagaram M, Royer AJ, Hu H, Rajhans A, Parthasarathy R, Krishnasamy SS, Mokshagundam SP, Kong M, Schwandt ML, Parajuli D, Cave MC, Vatsalya V. Illustration of Gut-Thyroid Axis in Alcohol Use Disorder: Interplay of Gut Dysfunction, Pro-Inflammatory Responses, and Thyroid Function. Cells 2022; 11:cells11193100. [PMID: 36231061 PMCID: PMC9563601 DOI: 10.3390/cells11193100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 09/21/2022] [Accepted: 09/28/2022] [Indexed: 11/16/2022] Open
Abstract
(1) Background: Heavy and chronic alcohol drinking leads to altered gut dysfunction, coupled with a pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by heavy and chronic alcohol intake; however, the mechanism for altered gut-derived changes in thyroid function has not been studied thus far. This study investigates the role of alcohol-induced gut dysfunction and pro-inflammatory cytokine profile in the thyroid function of patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n = 44) were divided into Gr.1, patients with normal thyroid-stimulating hormone (TSH) levels (n = 28, 0.8 ≤ TSH ≤ 3 mIU/L); and Gr.2, patients with clinically elevated TSH levels (n = 16, TSH > 3 mIU/L). Demographics, drinking measures, comprehensive metabolic panels, and candidate thyroid markers (TSH, circulating triiodothyronine (T3), and free thyroxine (fT4)) were analyzed. Gut-dysfunction-associated markers (lipopolysaccharide (LPS), LPS-binding protein (LBP), and soluble LPS-induced pathogen-associated protein (sCD14)), and candidate pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were also evaluated. (3) Results: Patients in both groups presented with a borderline overweight BMI category. Gr.2 reported numerically higher indices of chronic and heavy drinking patterns than Gr.1. The fT4 levels were elevated, while T3 was within normal limits in both groups. The gut dysfunction markers LBP and sCD14 were numerically elevated in Gr.2 vs. Gr.1, suggesting subtle ongoing changes. Candidate pro-inflammatory cytokines were significantly elevated in Gr.2, including IL-1 β, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect on the gut–immune–thyroid response (r = 0.896, 36 p = 0.002) on TSH levels in a multivariate regression model with LBP, sCD14, and PAI-1 levels as upstream variables in the gut–thyroid pathway. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area = 0.774, 39 p < 0.001) and TNF-α (area = 0.708, p = 0.017), among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4, as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and a lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation by employing the gut–brain axis. These results also emphasize potential directions to carefully evaluate thyroid dysregulation in the overall medical management of AUD.
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Affiliation(s)
- Manasa Sagaram
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA
- Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA
| | - Amor J. Royer
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA
- Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA
| | - Huirong Hu
- Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY 40202, USA
| | - Abhas Rajhans
- Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA
- Department of Neuroscience, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Ranganathan Parthasarathy
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA
- Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA
| | | | - Sri Prakash Mokshagundam
- Division of Endocrinology, Metabolism & Diabetes, University of Louisville, Louisville, KY 40202, USA
| | - Maiying Kong
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY 40202, USA
- University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY 40202, USA
| | | | - Dipendra Parajuli
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA
- Robley Rex VA Medical Center, Louisville, KY 40206, USA
| | - Matthew C. Cave
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA
- University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY 40202, USA
- Robley Rex VA Medical Center, Louisville, KY 40206, USA
| | - Vatsalya Vatsalya
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA
- Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA
- University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY 40202, USA
- National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA
- Correspondence: ; Tel.: +1-502-852-8928 or +1-502-488-0466
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Chiou WC, Lai WH, Cai YL, Du ML, Lai HM, Chen JC, Huang HC, Liu HK, Huang C. Gut microbiota-directed intervention with high-amylose maize ameliorates metabolic dysfunction in diet-induced obese mice. Food Funct 2022; 13:9481-9495. [PMID: 35993118 DOI: 10.1039/d2fo01211a] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Obesity is a chronic disease that may lead to the development of metabolic diseases, cardiovascular diseases, and cancers and has been predicted to affect one billion adults by 2030. Owing to the pivotal role of the gut microbiota in health, including metabolism and energy homeostasis, dietary fiber, the primary energy resource for the gut microbiota, not only helps reduce appetite and short-term food intake but also modulates the structure of the gut microbiota. In this study, we investigated whether high-amylose maize (HAM), with a particular amount of dietary fiber, improves dysmetabolism and gut microbiota dysbiosis in diet-induced obese mice. Promisingly, the HAM dietary intervention not only reduced body weight gain, adipocyte hypertrophy, and dyslipidemia but also mitigated non-alcoholic fatty liver disease, insulin resistance, impaired glucose tolerance, and inflammation in the liver and epididymal white adipose tissues in high-fat diet (HFD)-fed obese mice. In addition, the HAM dietary intervention ameliorated gut microbiota dysbiosis in HFD-fed mice. Changes in families, genera, and species of gut biota that have a relative abundance of 0.01% in at least one group were scrutinized. At the species level, HAM dietary intervention increased Bifidobacterium pseudolongum, Bifidobacterium animalis, Bifidobacterium bifidum, and Lactobacillus paraplantarum and decreased Streptococcus agalactiae, Mucispirillum schaedleri, and Alistipes indistinctus. This change in the gut microbiota driven by the HAM diet was strongly associated with obesity-related indices, highlighting the nutraceutical potential of HAM for improving overall metabolic health. Taken together, this study demonstrates the potential of the HAM diet for mediating metabolic syndrome and gut microbiota dysbiosis.
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Affiliation(s)
- Wei-Chung Chiou
- Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Wei-Han Lai
- Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Yu-Lin Cai
- Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Meng-Lun Du
- Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan
| | - Hsi-Mei Lai
- Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan
| | - Jui-Chieh Chen
- Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan
| | - Hsiu-Chen Huang
- Department of Applied Science, National Tsing Hua University South Campus, Hsinchu, Taiwan
- Center for Teacher Education, National Tsing Hua University, Hsinchu, Taiwan
| | - Hui-Kang Liu
- Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan
- PhD Program for the Clinical Drug Discovery from Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Cheng Huang
- Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Fu L, Qian Y, Shang Z, Sun X, Kong X, Gao Y. Antibiotics enhancing drug-induced liver injury assessed for causality using Roussel Uclaf Causality Assessment Method: Emerging role of gut microbiota dysbiosis. Front Med (Lausanne) 2022; 9:972518. [PMID: 36160154 PMCID: PMC9500153 DOI: 10.3389/fmed.2022.972518] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 08/22/2022] [Indexed: 11/13/2022] Open
Abstract
Drug-induced liver injury (DILI) is a disease that remains difficult to predict and prevent from a clinical perspective, as its occurrence is hard to fully explain by the traditional mechanisms. In recent years, the risk of the DILI for microbiota dysbiosis has been recognized as a multifactorial process. Amoxicillin-clavulanate is the most commonly implicated drug in DILI worldwide with high causality gradings based on the use of RUCAM in different populations. Antibiotics directly affect the structure and diversity of gut microbiota (GM) and changes in metabolites. The depletion of probiotics after antibiotics interference can reduce the efficacy of hepatoprotective agents, also manifesting as liver injury. Follow-up with liver function examination is essential during the administration of drugs that affect intestinal microorganisms and their metabolic activities, such as antibiotics, especially in patients on a high-fat diet. In the meantime, altering the GM to reconstruct the hepatotoxicity of drugs by exhausting harmful bacteria and supplementing with probiotics/prebiotics are potential therapeutic approaches. This review will provide an overview of the current evidence between gut microbiota and DILI events, and discuss the potential mechanisms of gut microbiota-mediated drug interactions. Finally, this review also provides insights into the "double-edged sword" effect of antibiotics treatment against DILI and the potential prevention and therapeutic strategies.
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Affiliation(s)
- Lihong Fu
- Central Laboratory, Department of Liver Diseases, ShuGuang Hospital, Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
- Institute of Infection Diseases, Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Yihan Qian
- Central Laboratory, Department of Liver Diseases, ShuGuang Hospital, Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Zhi Shang
- Central Laboratory, Department of Liver Diseases, ShuGuang Hospital, Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Xuehua Sun
- Central Laboratory, Department of Liver Diseases, ShuGuang Hospital, Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Xiaoni Kong
- Central Laboratory, Department of Liver Diseases, ShuGuang Hospital, Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Yueqiu Gao
- Central Laboratory, Department of Liver Diseases, ShuGuang Hospital, Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
- Institute of Infection Diseases, Shanghai University of Chinese Traditional Medicine, Shanghai, China
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Hawk Tea Flavonoids as Natural Hepatoprotective Agents Alleviate Acute Liver Damage by Reshaping the Intestinal Microbiota and Modulating the Nrf2 and NF-κB Signaling Pathways. Nutrients 2022; 14:nu14173662. [PMID: 36079919 PMCID: PMC9459715 DOI: 10.3390/nu14173662] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/30/2022] [Accepted: 09/01/2022] [Indexed: 11/17/2022] Open
Abstract
Hawk tea (Litsea coreana Levl. var. lanuginosa) is a traditional herbal tea in southwestern China, and was found to possess hepatoprotective effects in our previous study. However, it is unclear whether hawk tea flavonoids (HTF) can alleviate alcoholic liver damage (ALD). Firstly, we extracted and identified the presence of 191 molecules categorized as HTFs, with reynoutrin, avicularin, guaijaverin, cynaroside, and kaempferol-7-O-glucoside being the most prevalent. After taking bioavailability into consideration and conducting comprehensive sorting, the contribution of guaijaverin was the highest (0.016 mg/mice). Then, by daily intragastric administration of HTF (100 mg/kg/day) to the ALD mice, we found that HTF alleviated liver lipid deposition (inhibition of TG, TC, LDL-C) by reducing liver oxidative-stress-mediated inflammation (up-regulation NRF2/HO-1 and down-regulation TLR4/MyD88/NF-κB pathway) and reshaping the gut microbiota (Lactobacillus, Bifidobacterium, Bacillus increased). Overall, we found HTF could be a potential protective natural compound for treating ALD via the gut–liver axis and guaijaverin might be the key substance involved.
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30
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Jung JH, Kim SE, Suk KT, Kim DJ. Gut microbiota-modulating agents in alcoholic liver disease: Links between host metabolism and gut microbiota. Front Med (Lausanne) 2022; 9:913842. [PMID: 35935787 PMCID: PMC9354621 DOI: 10.3389/fmed.2022.913842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 07/04/2022] [Indexed: 11/13/2022] Open
Abstract
Alcoholic liver disease (ALD) involves a wide spectrum of diseases, including asymptomatic hepatic steatosis, alcoholic hepatitis, hepatic fibrosis, and cirrhosis, which leads to morbidity and mortality and is responsible for 0.9% of global deaths. Alcohol consumption induces bacterial translocation and alteration of the gut microbiota composition. These changes in gut microbiota aggravate hepatic inflammation and fibrosis. Alteration of the gut microbiota leads to a weakened gut barrier and changes host immunity and metabolic function, especially related to bile acid metabolism. Modulation and treatment for the gut microbiota in ALD has been studied using probiotics, prebiotics, synbiotics, and fecal microbial transplantation with meaningful results. In this review, we focused on the interaction between alcohol and gut dysbiosis in ALD. Additionally, treatment approaches for gut dysbiosis, such as abstinence, diet, pro-, pre-, and synbiotics, antibiotics, and fecal microbial transplantation, are covered here under ALD. However, further research through human clinical trials is warranted to evaluate the appropriate gut microbiota-modulating agents for each condition related to ALD.
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Affiliation(s)
- Jang Han Jung
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Sung-Eun Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
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31
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Park SH, Lee YS, Sim J, Seo S, Seo W. Alcoholic liver disease: a new insight into the pathogenesis of liver disease. Arch Pharm Res 2022; 45:447-459. [PMID: 35761115 DOI: 10.1007/s12272-022-01392-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 06/10/2022] [Indexed: 11/02/2022]
Abstract
Excessive alcohol consumption contributes to a broad clinical spectrum of liver diseases, from simple steatosis to end-stage hepatocellular carcinoma. The liver is the primary organ that metabolizes ingested alcohol and is exquisitely sensitive to alcohol intake. Alcohol metabolism is classified into two pathways: oxidative and non-oxidative alcohol metabolism. Both oxidative and non-oxidative alcohol metabolisms and their metabolites have toxic consequences for multiple organs, including the liver, adipose tissue, intestine, and pancreas. Although many studies have focused on the effects of oxidative alcohol metabolites on liver damage, the importance of non-oxidative alcohol metabolites in cellular damage has also been discovered. Furthermore, extrahepatic alcohol effects are crucial for providing additional information necessary for the progression of alcoholic liver disease. Therefore, studying the effects of alcohol-producing metabolites and interorgan crosstalk between the liver and peripheral organs that express ethanol-metabolizing enzymes will facilitate a comprehensive understanding of the pathogenesis of alcoholic liver disease. This review focuses on alcohol-metabolite-associated hepatotoxicity due to oxidative and non-oxidative alcohol metabolites and the role of interorgan crosstalk in alcoholic liver disease pathogenesis.
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Affiliation(s)
- Seol Hee Park
- College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea
| | - Young-Sun Lee
- Department of Internal Medicine, Korea University Medical Center, Seoul, Republic of Korea
| | - Jaemin Sim
- Lab of Hepatotoxicity, College of Pharmacy, Ewha Womans University, #52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03765, Republic of Korea
| | - Seonkyung Seo
- Lab of Hepatotoxicity, College of Pharmacy, Ewha Womans University, #52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03765, Republic of Korea
| | - Wonhyo Seo
- Lab of Hepatotoxicity, College of Pharmacy, Ewha Womans University, #52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03765, Republic of Korea.
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32
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The Role of Gut-Derived Lipopolysaccharides and the Intestinal Barrier in Fatty Liver Diseases. J Gastrointest Surg 2022; 26:671-683. [PMID: 34734369 PMCID: PMC8926958 DOI: 10.1007/s11605-021-05188-7] [Citation(s) in RCA: 97] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatosteatosis is the earliest stage in the pathogenesis of nonalcoholic fatty (NAFLD) and alcoholic liver disease (ALD). As NAFLD is affecting 10-24% of the general population and approximately 70% of obese patients, it carries a large economic burden and is becoming a major reason for liver transplantation worldwide. ALD is a major cause of morbidity and mortality causing 50% of liver cirrhosis and 10% of liver cancer related death. Increasing evidence has accumulated that gut-derived factors play a crucial role in the development and progression of chronic liver diseases. METHODS A selective literature search was conducted in Medline and PubMed, using the terms "nonalcoholic fatty liver disease," "alcoholic liver disease," "lipopolysaccharide," "gut barrier," and "microbiome." RESULTS Gut dysbiosis and gut barrier dysfunction both contribute to chronic liver disease by abnormal regulation of the gut-liver axis. Thereby, gut-derived lipopolysaccharides (LPS) are a key factor in inducing the inflammatory response of liver tissue. The review further underlines that endotoxemia is observed in both NAFLD and ALD patients. LPS plays an important role in conducting liver damage through the LPS-TLR4 signaling pathway. Treatments targeting the gut microbiome and the gut barrier such as fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, and intestinal alkaline phosphatase (IAP) represent potential treatment modalities for NAFLD and ALD. CONCLUSIONS The gut-liver axis plays an important role in the development of liver disease. Treatments targeting the gut microbiome and the gut barrier have shown beneficial effects in attenuating liver inflammation and need to be further investigated.
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Mesona chinensis Benth polysaccharides alleviates liver injury by beneficial regulation of gut microbiota in cyclophosphamide-induced mice. FOOD SCIENCE AND HUMAN WELLNESS 2022. [DOI: 10.1016/j.fshw.2021.07.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Zhang XN, Zhao N, Guo FF, Wang YR, Liu SX, Zeng T. Diallyl disulfide suppresses the lipopolysaccharide-driven inflammatory response of macrophages by activating the Nrf2 pathway. Food Chem Toxicol 2021; 159:112760. [PMID: 34896185 DOI: 10.1016/j.fct.2021.112760] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 11/07/2021] [Accepted: 12/05/2021] [Indexed: 12/18/2022]
Abstract
Lipopolysaccharide (LPS)-driven activation of Kupffer cells plays critical roles in the development of alcoholic liver disease (ALD). Accumulating evidence has revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) can modulate the polarization of macrophages. The current study aimed to investigate the roles of diallyl disulfide (DADS) in LPS-driven inflammation in vitro and in vivo. We found that DADS significantly increased the nuclear translocation of Nrf2 and the transcription of Nrf2 targets, including HO1, NQO1, and γ-GCSc, and suppressed degradation of Nrf2 protein. Besides, DADS significantly inhibited LPS-induced activation of NF-κB and MAPK, secretion of NO and TNF-α, and production of reactive oxygen species (ROS) in LPS-exposed RAW264.7 cells. In vivo study demonstrated that DADS significantly ameliorated liver damage in mice challenged with LPS, as shown by the inhibition of increases in serum aminotransferase activities, neutrophil infiltration, and NF-κB and NLRP3 inflammasome activation. Finally, knockout of Nrf2 abrogated the suppression of DADS on macrophage polarization and on liver injury induced by LPS. These findings reveal that DADS suppresses LPS-driven inflammatory response in the liver by activating Nrf2, which suggests that the protective effects of DADS against ALD may be attributed to the modulation of Kupffer cell polarization in the liver.
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Affiliation(s)
- Xiu-Ning Zhang
- Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Ning Zhao
- Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Fang-Fang Guo
- Department of Pharmacy, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Yi-Ran Wang
- Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Shi-Xuan Liu
- Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China
| | - Tao Zeng
- Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
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Cuesta CM, Pascual M, Pérez-Moraga R, Rodríguez-Navarro I, García-García F, Ureña-Peralta JR, Guerri C. TLR4 Deficiency Affects the Microbiome and Reduces Intestinal Dysfunctions and Inflammation in Chronic Alcohol-Fed Mice. Int J Mol Sci 2021; 22:ijms222312830. [PMID: 34884634 PMCID: PMC8657603 DOI: 10.3390/ijms222312830] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/23/2021] [Accepted: 11/25/2021] [Indexed: 12/21/2022] Open
Abstract
Chronic alcohol abuse causes an inflammatory response in the intestinal tract with damage to the integrity of the mucosa and epithelium, as well as dysbiosis in the gut microbiome. However, the role of gut bacteria in ethanol effects and how these microorganisms interact with the immune system are not well understood. The aim of the present study was to evaluate if TLR4 alters the ethanol-induced intestinal inflammatory response, and whether the response of this receptor affects the gut microbiota profile. We analyzed the 16S rRNA sequence of the fecal samples from wild-type (WT) and TLR4-knockout (TLR4-KO) mice with and without ethanol intake for 3 months. The results demonstrated that chronic ethanol consumption reduces microbiota diversity and causes dysbiosis in WT mice. Likewise, ethanol upregulates several inflammatory genes (IL-1β, iNOS, TNF-α) and miRNAs (miR-155-5p, miR-146a-5p) and alters structural and permeability genes (INTL1, CDH1, CFTR) in the colon of WT mice. Our results further demonstrated that TLR4-KO mice exhibit a different microbiota that can protect against the ethanol-induced activation of the immune system and colon integrity dysfunctions. In short, our results reveal that TLR4 is a key factor for determining the gut microbiota, which can participate in dysbiosis and the inflammatory response induced by alcohol consumption.
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Affiliation(s)
- Carlos M. Cuesta
- Department of Molecular and Cellular Pathology of Alcohol, Prince Felipe Research Center, 46012 Valencia, Spain; (C.M.C.); (M.P.); (I.R.-N.)
| | - María Pascual
- Department of Molecular and Cellular Pathology of Alcohol, Prince Felipe Research Center, 46012 Valencia, Spain; (C.M.C.); (M.P.); (I.R.-N.)
- Department of Physiology, School of Medicine and Dentistry, University of Valencia, 15 Avda. Blasco Ibanez, 46010 Valencia, Spain
| | - Raúl Pérez-Moraga
- Bioinformatics and Biostatistics Unit, Prince Felipe Research Center, 46012 Valencia, Spain; (R.P.-M.); (F.G.-G.)
| | - Irene Rodríguez-Navarro
- Department of Molecular and Cellular Pathology of Alcohol, Prince Felipe Research Center, 46012 Valencia, Spain; (C.M.C.); (M.P.); (I.R.-N.)
| | - Francisco García-García
- Bioinformatics and Biostatistics Unit, Prince Felipe Research Center, 46012 Valencia, Spain; (R.P.-M.); (F.G.-G.)
| | - Juan R. Ureña-Peralta
- Department of Molecular and Cellular Pathology of Alcohol, Prince Felipe Research Center, 46012 Valencia, Spain; (C.M.C.); (M.P.); (I.R.-N.)
- Correspondence: (J.R.U.-P.); (C.G.)
| | - Consuelo Guerri
- Department of Molecular and Cellular Pathology of Alcohol, Prince Felipe Research Center, 46012 Valencia, Spain; (C.M.C.); (M.P.); (I.R.-N.)
- Correspondence: (J.R.U.-P.); (C.G.)
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Panwar S, Sharma S, Tripathi P. Role of Barrier Integrity and Dysfunctions in Maintaining the Healthy Gut and Their Health Outcomes. Front Physiol 2021; 12:715611. [PMID: 34630140 PMCID: PMC8497706 DOI: 10.3389/fphys.2021.715611] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 08/27/2021] [Indexed: 01/08/2023] Open
Abstract
Mucosal surface layers are the critical borders throughout epithelial membranes. These epithelial cells segregate luminal material from external environments. However, mucosal linings are also accountable for absorbing nutrients and requiring specific barrier permeability. These functional acts positioned the mucosal epithelium at the epicenter of communications concerning the mucosal immune coordination and foreign materials, such as dietary antigens and microbial metabolites. Current innovations have revealed that external stimuli can trigger several mechanisms regulated by intestinal mucosal barrier system. Crucial constituents of this epithelial boundary are physical intercellular structures known as tight junctions (TJs). TJs are composed of different types transmembrane proteins linked with cytoplasmic adaptors which helps in attachment to the adjacent cells. Disruption of this barrier has direct influence on healthy or diseased condition, as barrier dysfunctions have been interrelated with the initiation of inflammation, and pathogenic effects following metabolic complications. In this review we focus and overview the TJs structure, function and the diseases which are able to influence TJs during onset of disease. We also highlighted and discuss the role of phytochemicals evidenced to enhance the membrane permeability and integrity through restoring TJs levels.
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Affiliation(s)
- Shruti Panwar
- Infection and Immunology, Translational Health Science and Technology Institute, National Capital Region (NCR) Biotech Science Cluster, Faridabad, India
| | - Sapna Sharma
- Gene Regulation Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Prabhanshu Tripathi
- Food Drug and Chemical Toxicology Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Toxicology Research, Lucknow, India
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Multiunit In Vitro Colon Model for the Evaluation of Prebiotic Potential of a Fiber Plus D-Limonene Food Supplement. Foods 2021; 10:foods10102371. [PMID: 34681420 PMCID: PMC8535099 DOI: 10.3390/foods10102371] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/01/2021] [Accepted: 10/03/2021] [Indexed: 12/12/2022] Open
Abstract
The search for new fiber supplements that can claim to be "prebiotic" is expanding fast, as the role of prebiotics and intestinal microbiota in well-being has been well established. This work explored the prebiotic potential of a novel fiber plus D-Limonene supplement (FLS) in comparison to fructooligosaccharides (FOS) over distal colonic fermentation with the in vitro model MICODE (multi-unit in vitro colon gut model). During fermentation, volatilome characterization and core microbiota quantifications were performed, then correlations among volatiles and microbes were interpreted. The results indicated that FLS generated positive effects on the host gut model, determining: (i) eubiosis; (ii) increased abundance of beneficial bacteria, as Bifidobacteriaceae; (iii) production of beneficial compounds, as n-Decanoic acid; (iv) reduction in detrimental bacteria, as Enterobaceteriaceae; (v) reduction in detrimental compounds, as skatole. The approach that we followed permitted us to describe the prebiotic potential of FLS and its ability to steadily maintain the metabolism of colon microbiota over time. This aspect is two-faced and should be investigated further because if a fast microbial turnover and production of beneficial compounds is a hallmark of a prebiotic, the ability to reduce microbiota changes and to reduce imbalances in the productions of microbial metabolites could be an added value to FLS. In fact, it has been recently demonstrated that these aspects could serve as an adjuvant in metabolic disorders and cognitive decline.
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Li B, Mao Q, Zhou D, Luo M, Gan R, Li H, Huang S, Saimaiti A, Shang A, Li H. Effects of Tea against Alcoholic Fatty Liver Disease by Modulating Gut Microbiota in Chronic Alcohol-Exposed Mice. Foods 2021; 10:1232. [PMID: 34071491 PMCID: PMC8228948 DOI: 10.3390/foods10061232] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 05/24/2021] [Accepted: 05/26/2021] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota dysbiosis has been a crucial contributor to the pathogenesis of alcoholic fatty liver disease (AFLD). Tea is a popular beverage worldwide and exerts antioxidant and anti-inflammatory activities, as well as hepatoprotective effects. However, the potential role of gut microbiota regulated by tea in the prevention and management of AFLD remains unclear. Here, the protective effects of oolong tea, black tea, and dark tea on AFLD and its regulation of gut microbiota in chronic alcohol-exposed mice were explored and investigated. The results revealed that tea supplementation significantly prevented liver steatosis, decreased oxidative stress and inflammation, and modulated gut microbiota in chronic alcohol-exposed mice, especially oolong tea and dark tea. However, black tea showed less effectiveness against liver injury caused by alcohol. Moreover, the diversity, structure and composition of chronic alcohol-disrupted gut microbiota were restored by the supplementation of oolong tea and dark tea based on the analysis of gut microbiota. Furthermore, the relationship between liver injury biochemical indicators and gut microbiota indicated that some specific bacteria, such as Bacteroides, Alloprevotella, and Parabacteroides were closely associated with AFLD. In addition, the phytochemical components in tea extracts were measured by high-performance liquid chromatography, which could contribute to preventive effects on AFLD. In summary, oolong tea and dark tea could prevent chronic alcohol exposure-induced AFLD by modulating gut microbiota.
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Affiliation(s)
- Bangyan Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Qianqian Mao
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Dandan Zhou
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Min Luo
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Renyou Gan
- Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu 610213, China;
- Key Laboratory of Coarse Cereal Processing (Ministry of Agriculture and Rural Affairs), Sichuan Engineering & Technology Research Center of Coarse Cereal Industralization, Chengdu University, Chengdu 610106, China
| | - Hangyu Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Siyu Huang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Adila Saimaiti
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Ao Shang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
| | - Huabin Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (B.L.); (Q.M.); (D.Z.); (M.L.); (H.L.); (S.H.); (A.S.); (A.S.)
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Zhong X, Cui P, Jiang J, Ning C, Liang B, Zhou J, Tian L, Zhang Y, Lei T, Zuo T, Ye L, Huang J, Chen H. Streptococcus, the Predominant Bacterium to Predict the Severity of Liver Injury in Alcoholic Liver Disease. Front Cell Infect Microbiol 2021; 11:649060. [PMID: 33816353 PMCID: PMC8010180 DOI: 10.3389/fcimb.2021.649060] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 03/01/2021] [Indexed: 12/20/2022] Open
Abstract
Background New evidence implies that the imbalance of gut microbiota is associated with the progression of alcoholic liver disease (ALD) and that the composition of gut microbiota is altered in ALD patients. However, the predominant bacterium in patients involved in the progress of ALD has not been identified. The purpose of this study is to investigate the predominant bacterium in the early and end-stages of ALD as well as the relationship between the bacterium and the degree of liver injury. Methods We enrolled 21 alcoholic fatty liver (AFL) patients, 17 alcoholic liver cirrhosis (ALC) patients and 27 healthy controls, and sequenced the 16S rRNA gene of their fecal microbiota. The gut microbiota composition and its relationship with the indicators of clinical hepatic function were assessed using canonical correspondence analysis (CCA), spearman correlation heatmap and multivariate association with linear (MaAsLin) Models. Results The composition and structure of gut microbiota changed greatly in different stages of ALD, and the degree of disorder was aggravated with the progression of ALD, even in the early stage. Moreover, the relative abundance of Streptococcus was highly enriched only in patients with ALC (P <0.001), and positively correlated with AST level (P = 0.029). The abundance of Streptococcus distinguished the liver injury of ALC patients from the controls with an area under the receiver-operating characteristic curve (AUC) of 0.877 (P < 0.001). Conclusions These findings indicate that the imbalance of gut microbiota exists at the early and end-stages of ALD, and the degree of disorder is aggravated with the progression of ALD. Streptococcus, as the predominant bacterium, may be a microbiological marker to evaluate the severity of liver injury in ALD patients.
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Affiliation(s)
- Xiaodan Zhong
- Geriatrics Digestion Department of Internal Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.,Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China
| | - Ping Cui
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China.,Life Science Institute, Guangxi Medical University, Nanning, China
| | - Junjun Jiang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China
| | - Chuanyi Ning
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China.,Nursing College, Guangxi Medical University, Nanning, China
| | - Bingyu Liang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China
| | - Jie Zhou
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China
| | - Li Tian
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China
| | - Yu Zhang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China
| | - Ting Lei
- Geriatrics Digestion Department of Internal Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.,Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China
| | - Taiping Zuo
- Geriatrics Digestion Department of Internal Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.,Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China
| | - Li Ye
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China.,Life Science Institute, Guangxi Medical University, Nanning, China
| | - Jiegang Huang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China
| | - Hui Chen
- Geriatrics Digestion Department of Internal Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.,Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China
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Nissen L, Casciano F, Chiarello E, Di Nunzio M, Bordoni A, Gianotti A. Colonic In Vitro Model Assessment of the Prebiotic Potential of Bread Fortified with Polyphenols Rich Olive Fiber. Nutrients 2021; 13:nu13030787. [PMID: 33673592 PMCID: PMC7997273 DOI: 10.3390/nu13030787] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/19/2021] [Accepted: 02/23/2021] [Indexed: 02/07/2023] Open
Abstract
The use of olive pomace could represent an innovative and low-cost strategy to formulate healthier and value-added foods, and bakery products are good candidates for enrichment. In this work, we explored the prebiotic potential of bread enriched with Polyphenol Rich Fiber (PRF), a defatted olive pomace byproduct previously studied in the European Project H2020 EcoProlive. To this aim, after in vitro digestion, the PRF-enriched bread, its standard control, and fructo-oligosaccharides (FOS) underwent distal colonic fermentation using the in vitro colon model MICODE (multi-unit colon gut model). Sampling was done prior, over and after 24 h of fermentation, then metabolomic analysis by Solid Phase Micro Extraction Gas Chromatography Mass Spectrometry (SPME GCMS), 16S-rDNA genomic sequencing of colonic microbiota by MiSeq, and absolute quantification of main bacterial species by qPCR were performed. The results indicated that PRF-enriched bread generated positive effects on the host gut model: (i) surge in eubiosis; (ii) increased abundance of beneficial bacterial groups, such as Bifidobacteriaceae and Lactobacillales; (iii) production of certain bioactive metabolites, such as low organic fatty acids; (iv) reduction in detrimental compounds, such as skatole. Our study not only evidenced the prebiotic role of PRF-enriched bread, thereby paving the road for further use of olive by-products, but also highlighted the potential of the in vitro gut model MICODE in the critical evaluation of functionality of food prototypes as modulators of the gut microbiota.
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Affiliation(s)
- Lorenzo Nissen
- CIRI-Interdepartmental Centre of Agri-Food Industrial Research, Alma Mater Studiorum-University of Bologna, Piazza G. Goidanich, 60, 47521 Cesena (FC), Italy; (M.D.N.); (A.B.); (A.G.)
- Correspondence: ; Tel.: +39-0547-338-146
| | - Flavia Casciano
- DiSTAL-Department of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, Piazza G. Goidanich, 60, 47521 Cesena (FC), Italy; (F.C.); (E.C.)
| | - Elena Chiarello
- DiSTAL-Department of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, Piazza G. Goidanich, 60, 47521 Cesena (FC), Italy; (F.C.); (E.C.)
| | - Mattia Di Nunzio
- CIRI-Interdepartmental Centre of Agri-Food Industrial Research, Alma Mater Studiorum-University of Bologna, Piazza G. Goidanich, 60, 47521 Cesena (FC), Italy; (M.D.N.); (A.B.); (A.G.)
- DiSTAL-Department of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, Piazza G. Goidanich, 60, 47521 Cesena (FC), Italy; (F.C.); (E.C.)
| | - Alessandra Bordoni
- CIRI-Interdepartmental Centre of Agri-Food Industrial Research, Alma Mater Studiorum-University of Bologna, Piazza G. Goidanich, 60, 47521 Cesena (FC), Italy; (M.D.N.); (A.B.); (A.G.)
- DiSTAL-Department of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, Piazza G. Goidanich, 60, 47521 Cesena (FC), Italy; (F.C.); (E.C.)
| | - Andrea Gianotti
- CIRI-Interdepartmental Centre of Agri-Food Industrial Research, Alma Mater Studiorum-University of Bologna, Piazza G. Goidanich, 60, 47521 Cesena (FC), Italy; (M.D.N.); (A.B.); (A.G.)
- DiSTAL-Department of Agricultural and Food Sciences, Alma Mater Studiorum-University of Bologna, Piazza G. Goidanich, 60, 47521 Cesena (FC), Italy; (F.C.); (E.C.)
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Impact of drinking alcohol on gut microbiota: recent perspectives on ethanol and alcoholic beverage. Curr Opin Food Sci 2021. [DOI: 10.1016/j.cofs.2020.10.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Zhang Z, Zeng P, Gao W, Wu R, Deng T, Chen S, Tian X. Exploration of the Potential Mechanism of Calculus Bovis in Treatment of Primary Liver Cancer by Network Pharmacology. Comb Chem High Throughput Screen 2021; 24:129-138. [PMID: 32772910 DOI: 10.2174/1386207323666200808172051] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 05/21/2020] [Accepted: 06/24/2020] [Indexed: 12/24/2022]
Abstract
AIM AND OBJECTIVE Calculus Bovis (CB) has been employed to treat diseases for a long time. It has been identified to play significant anti-inflammatory and anti-tumor roles. However, the mechanism of treating primary liver cancer (PLC) remains to be revealed. This study aims to clarify the molecules and mechanisms of CB in treating PLC. MATERIALS AND METHODS After oral bioavailability (OB) and drug-likeness (DL) screening, 15 small molecules were identified as the potential ingredients against PLC. Following this, related targets network constructions and pathways were applied to clarify the mechanism of CB in treating PLC. An in vitro experiment was carried out to identify the function of CB in treating PLC. RESULTS Eleven compounds of CB were identified that play an anti-PLC role, including oleanolic acid, ergosterol, ursolic acid, etc. The potential targets which were observed include IL6, MAPK-8, VEGFA, Caspase-3, etc. Further analysis showed that the mechanism of CB in the treatment of PLC involved apoptosis-related pathways and immune-related pathways. CONCLUSION In summary, the current study combines network pharmacology and in vitro experiments to reveal the mechanism of CB against PLC. We concluded that 11 ingredients of CB have an anti-PLC effect. Furthermore, CB plays a key role in treating PLC mainly by apoptosisrelated pathways and immune-related pathways. Our experiment verifies that CB promotes the apoptosis of SMMC-7721.
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Affiliation(s)
- Zhen Zhang
- Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
| | - Puhua Zeng
- Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha 410006, China
| | - Wenhui Gao
- School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
| | - Ruoxia Wu
- Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
| | - Tianhao Deng
- Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha 410006, China
| | - Siqin Chen
- Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha 410006, China
| | - Xuefei Tian
- Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
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Micó-Carnero M, Rojano-Alfonso C, Álvarez-Mercado AI, Gracia-Sancho J, Casillas-Ramírez A, Peralta C. Effects of Gut Metabolites and Microbiota in Healthy and Marginal Livers Submitted to Surgery. Int J Mol Sci 2020; 22:44. [PMID: 33375200 PMCID: PMC7793124 DOI: 10.3390/ijms22010044] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/18/2020] [Accepted: 12/20/2020] [Indexed: 12/12/2022] Open
Abstract
Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut-liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery.
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Affiliation(s)
- Marc Micó-Carnero
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.M.-C.); (C.R.-A.)
| | - Carlos Rojano-Alfonso
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.M.-C.); (C.R.-A.)
| | - Ana Isabel Álvarez-Mercado
- Departamento de Bioquímica y Biología Molecular II, Escuela de Farmacia, Universidad de Granada, 18071 Granada, Spain;
- Institut of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria ibs, GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
| | - Jordi Gracia-Sancho
- Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory IDIBAPS, 03036 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain
| | - Araní Casillas-Ramírez
- Hospital Regional de Alta Especialidad de Ciudad Victoria “Bicentenario 2010”, Ciudad Victoria 87087, Mexico;
- Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, Matamoros 87300, Mexico
| | - Carmen Peralta
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.M.-C.); (C.R.-A.)
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Regulating Intestinal Microbiota in the Prevention and Treatment of Alcohol-Related Liver Disease. Can J Gastroenterol Hepatol 2020; 2020:6629196. [PMID: 33381475 PMCID: PMC7759392 DOI: 10.1155/2020/6629196] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/29/2020] [Accepted: 12/08/2020] [Indexed: 02/06/2023] Open
Abstract
When alcohol-related liver disease occurs, the number and composition ratio of intestinal microorganisms will accordingly change. The alcohol-induced changes in the intestinal microbiota play a pivotal role in the process of developing the alcohol-related liver disease through the translocation of microbial products due to increased intestinal permeability. In recent years, therapeutic interventions with a concentration on regulating intestinal microbiota have been conducted for patients with alcohol-related liver disease. We aimed to provide a critical review and updates on the prevention and treatment of alcohol-related liver disease through regulating intestinal microbiota. A literature search was performed on the PubMed database for studies published in English about the therapeutic intervention with microbiota using animal models and patients with alcohol-related liver disease (1/2010-4/2020). The accumulating pieces of evidence suggest that the therapeutic use of probiotics, prebiotics, antibiotics, phages, or fecal microbial transplantation may have several influences on alcohol-related liver disease patients. Emergent data unveiled that these interventions can further regulate the composition of intestinal microbiota, minimize the negative impact of microbiota on the liver, and prevent disease progression from mild to severe alcoholic hepatitis, fibrosis, cirrhosis, or even liver cancer. The current review provides updates on the advances of therapeutic interventions with the effects of regulating intestinal microbiota on patients who have alcohol-related liver disease. In addition, the data gaps and research directions on further exploration of the role of intestinal microbiota for the management of the alcohol-related liver disease are also discussed.
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Plaza-Díaz J, Solís-Urra P, Rodríguez-Rodríguez F, Olivares-Arancibia J, Navarro-Oliveros M, Abadía-Molina F, Álvarez-Mercado AI. The Gut Barrier, Intestinal Microbiota, and Liver Disease: Molecular Mechanisms and Strategies to Manage. Int J Mol Sci 2020; 21:8351. [PMID: 33171747 PMCID: PMC7664383 DOI: 10.3390/ijms21218351] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 10/31/2020] [Accepted: 11/05/2020] [Indexed: 02/06/2023] Open
Abstract
Liver disease encompasses pathologies as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcohol liver disease, hepatocellular carcinoma, viral hepatitis, and autoimmune hepatitis. Nowadays, underlying mechanisms associating gut permeability and liver disease development are not well understood, although evidence points to the involvement of intestinal microbiota and their metabolites. Animal studies have shown alterations in Toll-like receptor signaling related to the leaky gut syndrome by the action of bacterial lipopolysaccharide. In humans, modifications of the intestinal microbiota in intestinal permeability have also been related to liver disease. Some of these changes were observed in bacterial species belonging Roseburia, Streptococcus, and Rothia. Currently, numerous strategies to treat liver disease are being assessed. This review summarizes and discusses studies addressed to determine mechanisms associated with the microbiota able to alter the intestinal barrier complementing the progress and advancement of liver disease, as well as the main strategies under development to manage these pathologies. We highlight those approaches that have shown improvement in intestinal microbiota and barrier function, namely lifestyle changes (diet and physical activity) and probiotics intervention. Nevertheless, knowledge about how such modifications are beneficial is still limited and specific mechanisms involved are not clear. Thus, further in-vitro, animal, and human studies are needed.
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Affiliation(s)
- Julio Plaza-Díaz
- Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada;
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18071 Granada, Spain
| | - Patricio Solís-Urra
- Faculty of Education and Social Sciences, Universidad Andres Bello, Viña del Mar 2531015, Chile;
| | - Fernando Rodríguez-Rodríguez
- IRyS Research Group, School of Physical Education, Pontificia Universidad Católica de Valparaíso, Valparaíso 2374631, Chile; (F.R.-R.); (J.O.-A.)
| | - Jorge Olivares-Arancibia
- IRyS Research Group, School of Physical Education, Pontificia Universidad Católica de Valparaíso, Valparaíso 2374631, Chile; (F.R.-R.); (J.O.-A.)
- Escuela de Pedagogía en Educación Física, Facultad de Educación, Universidad de las Américas, Santiago 8370035, Chile
| | - Miguel Navarro-Oliveros
- BioCritic. Group for Biomedical Research in Critical Care Medicine, 47005 Valladolid, Spain;
| | - Francisco Abadía-Molina
- Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain;
- Department of Cell Biology, School of Sciences, University of Granada, 18071 Granada, Spain
| | - Ana I. Álvarez-Mercado
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18071 Granada, Spain
- Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain;
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Gurwara S, Dai A, Ajami NJ, Graham DY, White DL, Chen L, Jang A, Chen E, El-Serag HB, Petrosino JF, Jiao L. Alcohol use alters the colonic mucosa-associated gut microbiota in humans. Nutr Res 2020; 83:119-128. [PMID: 33096423 DOI: 10.1016/j.nutres.2020.09.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 08/26/2020] [Accepted: 09/09/2020] [Indexed: 12/12/2022]
Abstract
Alcohol misuse is a risk factor for many adverse health outcomes. Alcohol misuse has been associated with an imbalance of gut microbiota in preclinical models and alcoholic diseases. We hypothesized that daily alcohol use would change the community composition and structure of the human colonic gut microbiota. Thirty-four polyp-free individuals donated 97 snap-frozen colonic biopsies. Microbial DNA was sequenced for the 16S ribosomal RNA gene hypervariable region 4. The SILVA database was used for operational taxonomic unit classification. Alcohol use was assessed using a food frequency questionnaire. We compared the biodiversity and relative abundance of the taxa among never drinkers (ND, n = 9), former drinkers (FD, n = 10), current light drinkers (LD, <2 drinks daily, n = 9), and current heavy drinkers (HD, ≥2 drinks daily, n = 6). False discovery rate-adjusted P values (q values) < .05 indicated statistical significance. HD had the lowest α diversity (Shannon index q value < 0.001), and HD's microbial composition differed the most from the other groups (P value = .002). LD had the highest relative abundance of Akkermansia (q values < 0.001). HD had the lowest relative abundance of Subdoligranulum, Roseburia, and Lachnospiraceaeunc91005 but the highest relative abundance of Lachnospiraceaeunc8895 (all q values < 0.05). The multivariable negative binomial regression model supported these observations. ND and FD had a similar microbial profile. Heavy alcohol use was associated with impaired gut microbiota that may partially mediate its effect on health outcomes.
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Affiliation(s)
- Shawn Gurwara
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
| | - Annie Dai
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
| | - Nadim J Ajami
- The Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
| | - David Y Graham
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Section of Gastroenterology, Michael E. DeBakey VA Medical Center, Houston, TX, USA.
| | - Donna L White
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Texas Medical Center Digestive Disease Center, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety, Houston, TX, USA; Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX, USA.
| | - Liang Chen
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety, Houston, TX, USA.
| | - Albert Jang
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
| | - Ellie Chen
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
| | - Hashem B El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Section of Gastroenterology, Michael E. DeBakey VA Medical Center, Houston, TX, USA; Texas Medical Center Digestive Disease Center, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety, Houston, TX, USA.
| | - Joseph F Petrosino
- The Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA; Texas Medical Center Digestive Disease Center, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
| | - Li Jiao
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Section of Gastroenterology, Michael E. DeBakey VA Medical Center, Houston, TX, USA; Texas Medical Center Digestive Disease Center, Houston, TX, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA; Center for Innovations in Quality, Effectiveness and Safety, Houston, TX, USA; Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX, USA.
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Mizuno Y, Ishikawa T, Ishida J, Kobayashi A, Konakahara Y, Kinoshita A, Hama H, Hokari A, Saruta M. The Molar Ratio of Total Branched-chain Amino Acids to Tyrosine Predicts a Digit Symbol Test Abnormality in Cirrhotic Patients. Intern Med 2020; 59:1695-1704. [PMID: 32296001 PMCID: PMC7434536 DOI: 10.2169/internalmedicine.4298-19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective We aimed to investigate the association between the digit symbol test (DST) and clinical characteristics, including the nutritional status of liver cirrhosis patients. Methods Fifty-nine cirrhotic patients without a history of overt hepatic encephalopathy were retrospectively evaluated. We examined neuropsychological abnormalities (NPAs) using the DST. We also estimated the detailed nutritional status using the Food Frequency Questionnaire (FFQ). The patients were divided into two groups according to their DST status: patients with normal DST scores (DST-Nor group, n=45) and those with abnormal DST scores (DST-Abn group, n=14). The clinical and nutritional findings of the two groups were compared. Results Overall, 14 (23.7%) patients had a DST abnormality. There were significant differences between the two groups in serum albumin (Alb; p=0.0043), valine (Val; p=0.0016), leucine (Leu; p=0.0078), isoleucine (Ile; p=0.0022), the molar ratio of total branched-chain amino acids to tyrosine (BTR; p=0.00025), total-bilirubin (T-Bil; p=0.0071), prothrombin time (%) (PT; p=0.028), and serum sodium (Na; p=0.035). A multivariate analysis found the BTR to be the only independent predictor of a DST abnormality (hazard ratio, 9.24; p<0.031). An FFQ analysis, revealed that the nutritional findings of patients with and without a DST abnormality, were similar. Conclusion The BTR was useful for predicting the risk of NPAs, as defined by a DST abnormality. The risk of NPAs may be estimated by monitoring the BTR.
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Affiliation(s)
- Yusuke Mizuno
- Department of Gastroenterology and Hepatology, The Jikei University Daisan Hospital, Japan
| | - Tomohisa Ishikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Japan
| | - Jinya Ishida
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Japan
| | - Akemi Kobayashi
- Clinical Nutritional Supports, Jikei University Hospital, Japan
| | | | - Akiyoshi Kinoshita
- Department of Gastroenterology and Hepatology, The Jikei University Daisan Hospital, Japan
| | - Hironobu Hama
- Clinical Nutritional Supports, Jikei University Hospital, Japan
| | - Atsushi Hokari
- Department of Gastroenterology and Hepatology, The Jikei University Katsushika Medical Center, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Japan
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Rao BC, Lou JM, Wang WJ, Li A, Cui GY, Yu ZJ, Ren ZG. Human microbiome is a diagnostic biomarker in hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2020; 19:109-115. [PMID: 32037278 DOI: 10.1016/j.hbpd.2020.01.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 01/13/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Increasing evidence indicates a close relationship between HCC and the human microbiota. Herein, we reviewed the important potential of the human microbiota as a diagnostic biomarker of HCC. DATA SOURCES Several innovative studies have investigated the characteristics of the gut and oral microbiomes in patients with HCC and proposed that the human microbiome has the potential to be a diagnostic biomarker of HCC. Literature from February 1999 to February 2019 was searched in the PubMed database using the keywords "microbiota" or "microbiome" or "microbe" and "liver cancer" or "hepatocellular carcinoma", and the results of clinical and experimental studies were analyzed. RESULTS Specific changes occur in the human microbiome of patients with HCC. Moreover, the gut microbiome and oral microbiome can be used as non-invasive diagnostic biomarkers for HCC. Furthermore, they also have certain diagnostic potential for precancerous diseases of HCC. The diagnostic potential of the blood microbiota and ascites microbiota in HCC will be gradually discovered in the future. CONCLUSIONS The human microbiome is valuable to the diagnosis of HCC and provides a novel strategy for targeted therapy of HCC. The human microbiome may be widely used in the diagnosis, treatment and prognosis for multiple system diseases or cancers in the future.
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Affiliation(s)
- Ben-Chen Rao
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Jia-Min Lou
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Wei-Jie Wang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Ang Li
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Guang-Ying Cui
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Zu-Jiang Yu
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Zhi-Gang Ren
- Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Gene Hospital of Henan Province; Precision Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
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Rodríguez-Rabassa M, López P, Sánchez R, Hernández C, Rodríguez C, Rodríguez-Santiago RE, Orengo JC, Green V, Yamamura Y, Rivera-Amill V. Inflammatory Biomarkers, Microbiome, Depression, and Executive Dysfunction in Alcohol Users. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17030689. [PMID: 31973090 PMCID: PMC7037324 DOI: 10.3390/ijerph17030689] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 01/11/2020] [Accepted: 01/13/2020] [Indexed: 02/07/2023]
Abstract
Alcohol-related disorders (ARD) are highly prevalent among Latin American-Caribbean countries. Mental disorders are common comorbidities in individuals with ARD. However, the etiology of the association between ARD and mental disorders remains unclear. We examined the association of inflammatory cytokines, microbiome, and other biomakers with measures of depression, social anxiety, and executive functions. We observed a significant increase in cytokine and chemokine expression levels in saliva and plasma in the alcohol group (AG) samples. Also, the salivary bacterial composition in the AG revealed an abundance of Prevotella. Depression symptomatology was markedly higher in the AG, but social anxiety levels were negligible. AG also exhibited executive dysfunctions, which negatively correlated with increased plasma levels of pro-inflammatory cytokines and increased salivary concentrations of Prevotella bacteria. Our study suggests that chronic alcohol use correlates with executive dysfunction, immune system dysregulation, and dysbiosis of the salivary microbiota. Additional studies are needed to understand the role of the microbiome and inflammation in alcohol use and mental comorbidities.
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Affiliation(s)
- Mary Rodríguez-Rabassa
- Center for Research Resources, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (M.R.-R.); (P.L.); (R.S.); (R.E.R.-S.); (Y.Y.)
- Clinical Psychology Program, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (C.H.); (C.R.)
| | - Pablo López
- Center for Research Resources, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (M.R.-R.); (P.L.); (R.S.); (R.E.R.-S.); (Y.Y.)
| | - Raphael Sánchez
- Center for Research Resources, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (M.R.-R.); (P.L.); (R.S.); (R.E.R.-S.); (Y.Y.)
| | - Cyanela Hernández
- Clinical Psychology Program, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (C.H.); (C.R.)
| | - Cesarly Rodríguez
- Clinical Psychology Program, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (C.H.); (C.R.)
| | - Ronald E. Rodríguez-Santiago
- Center for Research Resources, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (M.R.-R.); (P.L.); (R.S.); (R.E.R.-S.); (Y.Y.)
| | - Juan C. Orengo
- Public Health Program, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (J.C.O.); (V.G.)
| | - Vivian Green
- Public Health Program, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (J.C.O.); (V.G.)
| | - Yasuhiro Yamamura
- Center for Research Resources, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (M.R.-R.); (P.L.); (R.S.); (R.E.R.-S.); (Y.Y.)
| | - Vanessa Rivera-Amill
- Center for Research Resources, Ponce Health Sciences University-Ponce Research Institute, Ponce, PR 00716-2348, USA; (M.R.-R.); (P.L.); (R.S.); (R.E.R.-S.); (Y.Y.)
- Correspondence: ; Tel.: +1-(787)-841-5150; Fax: +1-(787)-841-5159
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50
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Cornide-Petronio ME, Álvarez-Mercado AI, Jiménez-Castro MB, Peralta C. Current Knowledge about the Effect of Nutritional Status, Supplemented Nutrition Diet, and Gut Microbiota on Hepatic Ischemia-Reperfusion and Regeneration in Liver Surgery. Nutrients 2020; 12:284. [PMID: 31973190 PMCID: PMC7071361 DOI: 10.3390/nu12020284] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 01/13/2020] [Accepted: 01/15/2020] [Indexed: 02/06/2023] Open
Abstract
Ischemia-reperfusion (I/R) injury is an unresolved problem in liver resection and transplantation. The preexisting nutritional status related to the gut microbial profile might contribute to primary non-function after surgery. Clinical studies evaluating artificial nutrition in liver resection are limited. The optimal nutritional regimen to support regeneration has not yet been exactly defined. However, overnutrition and specific diet factors are crucial for the nonalcoholic or nonalcoholic steatohepatitis liver diseases. Gut-derived microbial products and the activation of innate immunity system and inflammatory response, leading to exacerbation of I/R injury or impaired regeneration after resection. This review summarizes the role of starvation, supplemented nutrition diet, nutritional status, and alterations in microbiota on hepatic I/R and regeneration. We discuss the most updated effects of nutritional interventions, their ability to alter microbiota, some of the controversies, and the suitability of these interventions as potential therapeutic strategies in hepatic resection and transplantation, overall highlighting the relevance of considering the extended criteria liver grafts in the translational liver surgery.
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Affiliation(s)
| | - Ana Isabel Álvarez-Mercado
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain;
- Institute of Nutrition and Food Technology “José Mataix,” Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n, 18016 Armilla, Granada, Spain
- Instituto de Investigación Biosanitaria ibs, GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
| | - Mónica B. Jiménez-Castro
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.E.C.-P.); (M.B.J.-C.)
| | - Carmen Peralta
- Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.E.C.-P.); (M.B.J.-C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain
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