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Alhouei B, Eslamian G, Mohtadi M. A Systematic Review of the Effects of Probiotics and Synbiotics on Infection Incidence after Liver Transplant Surgery. Prev Nutr Food Sci 2025; 30:101-109. [PMID: 40352302 PMCID: PMC12061535 DOI: 10.3746/pnf.2025.30.2.101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/20/2025] [Accepted: 02/10/2025] [Indexed: 05/14/2025] Open
Abstract
Among organ transplant operations, liver transplantation (LTX) has one of the highest risks of postoperative infection. This study aimed to systematically review the current evidence on the use of probiotics and synbiotics in reducing the incidence of postoperative infections in liver transplant recipients. A systematic search was performed to identify studies that investigated the role of probiotics and synbiotics in reducing postoperative infection rates in liver transplant recipients. Eight studies that qualified were included in the review. The results showed that probiotics and synbiotics effectively reduced the overall infection rates in liver transplant patients compared with the placebo or control groups. This positive effect might be attributed to improved intestinal barrier function, gut microbiota restoration, and decreased inflammation. Furthermore, probiotic treatment was associated with shorter durations of antibiotic use and hospital stays. The use of probiotics and synbiotics after LTX holds promise in decreasing postoperative infections and providing substantial advantages for patients. Probiotics have been shown to boost the levels of beneficial bacterial, decrease inflammation, fortify the intestinal barrier, lessen oxidative stress, and improve the generation of anti-inflammatory short-chain fatty acids. However, more extensive research is needed to identify the most effective probiotic strains and evaluate their effectiveness in this specific patient demographic.
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Affiliation(s)
- Barbod Alhouei
- Student Research Committee, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran 1981619573, Iran
| | - Ghazaleh Eslamian
- Department of Cellular and Molecular Nutrition, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran 1981619573, Iran
| | - Mahshad Mohtadi
- Student Research Committee, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran 1981619573, Iran
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Ververeli CL, Dimitroglou Y, Soulaidopoulos S, Cholongitas E, Aggeli C, Tsioufis K, Tousoulis D. Cardiac Remodeling and Arrhythmic Burden in Pre-Transplant Cirrhotic Patients: Pathophysiological Mechanisms and Management Strategies. Biomedicines 2025; 13:812. [PMID: 40299454 PMCID: PMC12025098 DOI: 10.3390/biomedicines13040812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Revised: 03/22/2025] [Accepted: 03/25/2025] [Indexed: 04/30/2025] Open
Abstract
Background: Chronic liver disease (CLD) and cirrhosis contribute to approximately 2 million deaths annually, with primary causes including alcohol-related liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and chronic hepatitis B and C infections. Among these, MASLD has emerged as a significant global health concern, closely linked to metabolic disorders and a leading cause of liver failure and transplantation. Objective: This review aims to highlight the interplay between cirrhosis and cardiac dysfunction, emphasizing the pathophysiology, diagnostic criteria, and management of cirrhotic cardiomyopathy (CCM). Methods: A comprehensive literature review was conducted to evaluate the hemodynamic and structural cardiac alterations in cirrhosis. Results: Cirrhosis leads to portal hypertension and systemic inflammation, contributing to CCM, which manifests as subclinical cardiac dysfunction, impaired contractility, and electrophysiological abnormalities. Structural changes, such as increased left ventricular mass, myocardial fibrosis, and ion channel dysfunction, further impair cardiac function. Vasodilation in the splanchnic circulation reduces peripheral resistance, triggering compensatory tachycardia, while the activation of the renin-angiotensin-aldosterone system (RAAS) promotes fluid retention and increases cardiac preload. Chronic inflammation and endotoxemia exacerbate myocardial dysfunction. The 2005 World Congress of Gastroenterology (WCG) and the 2019 Cirrhotic Cardiomyopathy Consortium (CCC) criteria provide updated diagnostic frameworks that incorporate global longitudinal strain (GLS) and tissue Doppler imaging (TDI). Prolonged QT intervals and arrhythmias are frequently observed. Managing heart failure in cirrhotic patients remains complex due to intolerance to afterload-reducing agents, and beta-blockers require careful use due to potential systemic hypotension. The interaction between CCM and major interventions, such as transjugular intrahepatic portosystemic shunt (TIPS) and orthotopic liver transplantation (OLT), highlights the critical need for thorough preoperative cardiac evaluation and vigilant postoperative monitoring. Conclusions: CCM is a frequently underdiagnosed yet significant complication of cirrhosis, impacting prognosis, particularly post-liver transplantation. Early identification using echocardiography and thorough evaluations of arrhythmia risk in cirrhotic patients are critical for optimizing management strategies. Future research should focus on targeted therapeutic approaches to mitigate the cardiac burden in cirrhotic patients and improve clinical outcomes.
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Affiliation(s)
- Charilila-Loukia Ververeli
- 1st Department of Cardiology, Hippokrateio General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (C.-L.V.); (S.S.); (C.A.); (K.T.); (D.T.)
| | - Yannis Dimitroglou
- 1st Department of Cardiology, Hippokrateio General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (C.-L.V.); (S.S.); (C.A.); (K.T.); (D.T.)
| | - Stergios Soulaidopoulos
- 1st Department of Cardiology, Hippokrateio General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (C.-L.V.); (S.S.); (C.A.); (K.T.); (D.T.)
| | - Evangelos Cholongitas
- 1st Department of Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Constantina Aggeli
- 1st Department of Cardiology, Hippokrateio General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (C.-L.V.); (S.S.); (C.A.); (K.T.); (D.T.)
| | - Konstantinos Tsioufis
- 1st Department of Cardiology, Hippokrateio General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (C.-L.V.); (S.S.); (C.A.); (K.T.); (D.T.)
| | - Dimitris Tousoulis
- 1st Department of Cardiology, Hippokrateio General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (C.-L.V.); (S.S.); (C.A.); (K.T.); (D.T.)
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Xu X, Zhu T, Jing C, Jiang M, Fu Y, Xie F, Meng Q, Li J. Hepatic encephalopathy treatment after transjugular intrahepatic portosystemic shunt: a new perspective on the gut microbiota. Front Med (Lausanne) 2025; 12:1423780. [PMID: 40124683 PMCID: PMC11926149 DOI: 10.3389/fmed.2025.1423780] [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: 11/23/2024] [Accepted: 02/24/2025] [Indexed: 03/25/2025] Open
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) placement alleviates portal hypertension symptoms. Hepatic encephalopathy (HE) is a common complication of TIPS, impacting patient quality of life and the healthcare burden. Post-TIPS HE is associated with portosystemic shunting, elevated blood ammonia levels, and inflammation. Increasing attention has been given to the liver and intestinal circulation in recent years. An imbalance in intestinal microecology plays a role in the occurrence of HE and may be a new target for treatment. This review discusses the causes, diagnosis, and treatment strategies for post-TIPS HE and focuses on exploring treatment strategies and their relationships with the gut microbiota, suggesting an innovative approach to address this complication.
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Affiliation(s)
- Xiaotong Xu
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Tong Zhu
- Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Changyou Jing
- Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Minjie Jiang
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yunlai Fu
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Fang Xie
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Qinghua Meng
- Department of Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jianjun Li
- Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
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Adjah J, D. Musimbi Z, Mugo RM, Midha A, Hartmann S, Rausch S. Liver-draining portal lymph node responds to enteric nematode infection by generating highly parasite-specific follicular T helper and B cell responses. Front Immunol 2025; 16:1483274. [PMID: 40092986 PMCID: PMC11906467 DOI: 10.3389/fimmu.2025.1483274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 01/27/2025] [Indexed: 03/19/2025] Open
Abstract
Introduction While research on the gut-liver axis in non-communicable liver diseases has expanded exponentially, few studies have investigated the liver-gut relationship in the context of gastrointestinal nematode infections. This study aimed to determine whether liver-draining lymph nodes (LLNs) contribute to the immune response against a strictly enteric nematode infection. Methods We analyzed the cellular and functional immune responses in the portal (PLN) and celiac (CLN) liver-draining lymph nodes following infection with the small intestinal nematode Heligmosomoides (polygyrus) bakeri (H. bakeri). The composition of dendritic cells and CD4+ T cell subsets in LLNs was compared to the mesenteric lymph nodes (MLN), the primary draining site of gut infections. Additionally, we examined Th2 effector cell expansion, plasmablast generation, and B cell activation across these lymphoid sites. Results Both PLN and CLN exhibited increased cellularity at d14 post-infection. The immune profile in CLN closely resembled that of MLN, characterized by a robust expansion of GATA-3+ Th2 effector cells at days 6 and 14 post-infection. This was accompanied by an early plasmablast response, producing low-affinity IgG1 antibodies targeting immune-dominant excretory-secretory (ES) products. In contrast, PLN showed weaker Th2 responses and lower early plasma cell responses compared to MLN and CLN. However, PLN displayed strong follicular T helper (TFH) activity, with a B cell profile biased toward germinal center reactions. This led to high-affinity IgG1 antibodies specifically binding VAL-1 and ACE-1. Discussion These findings demonstrate, for the first time, that liver-draining lymph nodes actively participate in the adaptive immune response to enteric nematode infections. While MLN and CLN function synergistically in generating early Th2 effector cells and rapid extrafollicular IgG1+ plasma cell responses, PLN specializes in TFH-driven germinal center reactions and affinity maturation.
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Affiliation(s)
| | | | | | | | | | - Sebastian Rausch
- Department of Veterinary Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany
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Wang Y, Ma H, Li H, Huang Y, Tang Y, Tang X, Sun P, Tan Z, Pang H, Yang F. Selenium-Enriched Lactiplantibacillus plantarum ZZU 8-12 Regulates Intestinal Microbiota and Inhibits Acute Liver Injury. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10459-9. [PMID: 39875778 DOI: 10.1007/s12602-025-10459-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2025] [Indexed: 01/30/2025]
Abstract
Intake of certain Lactiplantibacillus strains was recognized as a potential strategy for acute liver injury (ALI) prevention. This study is aimed at developing a selenium-enriched Lactiplantibacillus strain-based ALI prevention strategy. L. plantarum ZZU 8-12 was isolated from human fecal sample and screened out based on its adaption to intestinal microenvironment, inhibitive capability against pathogenic bacteria, and in vivo anti-inflammation response in DSS-induced colitis mice model. The strain was applied as a producer of nano selenium particles to produce selenium-enriched L. plantarum ZZU 8-12. Intake of selenium-enriched L. plantarum ZZU 8-12 upregulated the abundance of short-chain fatty acid-producing genera including Lactiplantibacillus, Phascolarctobacterium, Butyricicoccus, and Clostridiales bacterium in fecal microbiota and thus inhibited ALI induced by CCL4 injection in mice. This study drew the potential for selenium-enriched L. plantarum ZZU 8-12 as an ingredient for ALI protection.
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Affiliation(s)
- Yanping Wang
- Henan Key Laboratory of Ion Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Hengyu Ma
- Henan Key Laboratory of Ion Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China
- Department of Medical Equipment, Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, 450000, Zhengzhou, China
| | - Haolong Li
- Henan Key Laboratory of Ion Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Yuhang Huang
- Henan Key Laboratory of Ion Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Yupeng Tang
- Henan Key Laboratory of Ion Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Xiaoxue Tang
- Henan Key Laboratory of Ion Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Pintian Sun
- Henan Key Laboratory of Ion Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Zhongfang Tan
- Henan Key Laboratory of Ion Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Huili Pang
- Henan Key Laboratory of Ion Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Fengyuan Yang
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China.
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Chen J, Song Y, Zeng W, Wang L, Qin J, Fang L, Ding Y. RESEARCH PROGRESS ON THE ROLE OF GUT MICROBIOTA AND ITS METABOLITES IN THE OCCURRENCE AND DEVELOPMENT OF SEPTIC-ASSOCIATED LIVER INJURY. Shock 2025; 63:4-10. [PMID: 39158846 DOI: 10.1097/shk.0000000000002441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/20/2024]
Abstract
ABSTRACT Sepsis is a life-threatening organ dysfunction that occurs due to a dysregulated host response to infection. Septic-associated liver injury (SALI) has been closely linked to the prognosis and mortality of sepsis. Recent investigations have delved into the gut-liver axis and its association with SALI, identifying its pivotal role in the gut microbiota. Bacterial translocation and the onset of SALI can occur due to an imbalance in the gut microbiota, impairing the function of the gut barrier. Moreover, their metabolites might exacerbate or initiate SALI by modulating immune responses. Nevertheless, interventions to restore the balance of the gut microbiota, such as the administration of probiotics, fecal microbiota transplantation, or dietary adjustments, may ameliorate SALI and enhance the prognosis and survival rates of septic patients. This review aimed to elucidate the function of the gut microbiota in the genesis and procession of SALI and its potential therapeutic value, offering a deeper understanding of the pathogenesis and therapeutic avenues for SALI.
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Affiliation(s)
- Jiangtao Chen
- Department of Intensive Care Unit, Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Yu Song
- Department of Hepatology, Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Wenqing Zeng
- Department of Intensive Care Unit, Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Lei Wang
- Department of Intensive Care Unit, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang Province, China
| | - Jinyan Qin
- Department of Intensive Care Unit, Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Lexin Fang
- Department of Intensive Care Unit, Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
| | - Yueping Ding
- Department of Intensive Care Unit, Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
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Cui Z, Zhang M, Meng Q, Wu X, Li M. Preparation, in vitro and in vivo assessment of novel carvacrol@pro-phytomicelles for the treatment of Salmonella enteritidis infection in mice. Int J Pharm 2024; 667:124861. [PMID: 39461679 DOI: 10.1016/j.ijpharm.2024.124861] [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: 08/20/2024] [Revised: 10/14/2024] [Accepted: 10/20/2024] [Indexed: 10/29/2024]
Abstract
In livestock and poultry farming, the use of antibiotics has been abused, which seriously endangers human health. Thus, antibiotic alternatives are urgently needed. The phytochemical carvacrol (CAR) has attracted attention as an antibiotic alternative due to its excellent antibacterial activity and anti-inflammatory activity. However, CAR has high volatility and low water solubility, which seriously affect its antibacterial activity. In this study, two plant-derived small-molecule phytochemicals-glycyrrhizin and rebaudioside A-were selected as nanocarriers for the preparation of a novel solid pro-phytomicelle formulation named as CAR@PP. Using a simple fabrication method, the encapsulation efficiency of CAR reached 98.74 ± 1.14 %. CAR@PP was found to rapidly dissolve in water, resulting in a transparent solution (named as CAR@M) and a 59-fold increase in solubility compared to CAR. CAR@M contained uniform nanoparticles with a particle size, polydispersity index, and zeta potential of 3.52 ± 0.93 nm, 0.17 ± 0.01, and -10.63 ± 0.45 mV, respectively. The in vitro antibacterial activity of CAR@M was evaluated, and the minimum inhibitory concentration for the tested strains was 125-250 μg/ml. The antibacterial mechanisms were found that CAR@M disrupted the bacterial wall and biomembranes and efficiently inhibited bacterial biofilm growth. To the in vivo activity evaluation, treatment with 50 mg/kg CAR@M could effectively improve bacterial liver abscesses, decrease the inflammatory cytokine levels in the liver and cecum, and reduce the bacterial load in the liver and feces in Salmonella enteritidis-infected mice. In conclusion, CAR@PP is a promising alternative to antibiotics in livestock and poultry farming warranting further research.
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Affiliation(s)
- Zhengwei Cui
- College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
| | | | | | - Xianggen Wu
- College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China.
| | - Mengshuang Li
- Qingdao Women and Children's Hospital, Qingdao, China.
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Efremova I, Alieva A, Maslennikov R, Poluektova E, Zharkova M, Kudryavtseva A, Krasnov G, Zharikov Y, Nerestyuk Y, Karchevskaya A, Ivashkin V. Akkermansia muciniphila is associated with normal muscle mass and Eggerthella is related with sarcopenia in cirrhosis. Front Nutr 2024; 11:1438897. [PMID: 39539377 PMCID: PMC11557486 DOI: 10.3389/fnut.2024.1438897] [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: 05/26/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Sarcopenia and gut dysbiosis are common in cirrhosis. The aim is to study the correlations between the gut microbiota taxa and muscle mass level in cirrhosis. METHODS The study included 40 cirrhosis patients including 18 patients with sarcopenia. The gut microbiota composition was assessed using amplicon sequencing of the hypervariable V3-V4 regions of the 16S rRNA gene. The skeletal muscle mass, subcutaneous and visceral fat levels were assessed with abdominal computed tomography as skeletal muscle, subcutaneous and visceral fat indices (SMI, SFI and VFI). RESULTS Patients with sarcopenia had more relative abundance (RA) of Agathobacter, Anaerostipes, Butyricicoccus, Dorea, Eggerthella, Microbacteriaceae, Veillonella and less RA of Akkermansiaceae, Akkermansia muciniphila, Verrucomicrobiae and Bilophila compared to patients with normal muscle mass. SMI directly correlated with RA of Akkermansia, Alistipes indistinctus, Anaerotruncus, Atopobiaceae, Bacteroides clarus, Bacteroides salyersiae, Barnesiellaceae, Bilophila wadsworthia, Pseudomonadota, Olsenella, and Parabacteroides distasonis, and negatively correlated with RA of Anaerostipes and Eggerthella. Sarcopenia was detected in 20.0% patients whose gut microbiota had Akkermansia but not Eggerthella, and in all the patients, whose gut microbiota had Eggerthella but not Akkermansia. The Akkermansia and Eggerthella abundances were independent determinants of SMI. RA of Akkermansia, Akkermansia muciniphila, Akkermansiaceae, Bacteroides salyersiae, Barnesiella, Bilophila, Desulfobacterota, Verrucomicrobiota and other taxa correlated positively and RA of Anaerovoracaceae, Elusimicrobiaceae, Elusimicrobium, Kiritimatiellae, Spirochaetota, and other taxa correlated negatively with the SFI. RA of Alistripes, Romboutsia, Succinivibrio, and Succinivibrionaceae correlated positively and RA of Bacteroides thetaiotaomicron correlated negatively with VFI. CONCLUSION The muscle mass level in cirrhosis correlates with the abundance of several gut microbiota taxa, of which Akkermansia and Eggerthella seems to be the most important.
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Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russia
| | - Aliya Alieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russia
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow, Russia
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russia
| | - Anna Kudryavtseva
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology of Russian Academy of Sciences, Moscow, Russia
| | - George Krasnov
- Post-Genomic Research Laboratory, Engelhardt Institute of Molecular Biology of Russian Academy of Sciences, Moscow, Russia
| | - Yury Zharikov
- Department of Anatomy, Sechenov University, Moscow, Russia
| | | | - Anna Karchevskaya
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russia
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Yang W, Guo G, Sun C. Therapeutic potential of rifaximin in liver diseases. Biomed Pharmacother 2024; 178:117283. [PMID: 39126775 DOI: 10.1016/j.biopha.2024.117283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/05/2024] [Accepted: 08/08/2024] [Indexed: 08/12/2024] Open
Abstract
Rifaximin, derived from rifamycin, is a broad-spectrum antibiotic by inhibiting bacterial RNA synthesis. Rifaximin has a very low intestinal absorption and exerts its antimicrobial activity primarily in the intestinal tract. It regulates the gut microbiota with limited side effects systemically. Rifaximin has been recommended for the treatment of hepatic encephalopathy but some studies shed light on its medicinal effects in many other diseases. For instance, rifaximin may suppress the progression of liver fibrosis and its related complications, and ameliorate metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease, etc. Rifaximin can also mediate anti-inflammation, antiproliferation, and proapoptotic events by activating pregnane X receptor, which is efficious in cancers such as colon cancer. In addition, some investigations have shown rifaximin may play a therapeutic role in various autoimmune and neurological disorders. However, these findings still need more real-world practices and in-depth investigations to obtain more precise indications and fully elucidate the multifaceted potentials of rifaximin.
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Affiliation(s)
- Wanting Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin 300308, China
| | - Gaoyue Guo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin 300308, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin 300308, China.
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10
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Sun S, Zhang G, Lv S, Sun J. Potential mechanisms of traditional Chinese medicine in the treatment of liver cirrhosis: a focus on gut microbiota. Front Microbiol 2024; 15:1407991. [PMID: 39234554 PMCID: PMC11371771 DOI: 10.3389/fmicb.2024.1407991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 07/29/2024] [Indexed: 09/06/2024] Open
Abstract
Cirrhosis, a pathological stage that develops from various chronic liver diseases, is characterized by liver fibrosis, pseudolobular formation, and chronic inflammation. When it progresses to the decompensated phase, the mortality rate of cirrhosis can reach 80%. The role of gut microbiota in the progression of liver diseases has received significant attention. Numerous studies have shown that regulating gut microbiota has significant therapeutic effects on preventing and reversing liver cirrhosis. This article reviewed the mechanisms by which gut microbiota influence liver cirrhosis, explaining the effective therapeutic effects of traditional Chinese medicine. Through multi-directional regulation involving signaling pathways, gut microbiota diversity, and restoration of intestinal barrier function, traditional Chinese medicine has been promising in ameliorating liver cirrhosis, providing treatment options and pharmacological guidance for the occurrence and development of liver cirrhosis.
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Affiliation(s)
- Siyuan Sun
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
| | - Guangheng Zhang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shimeng Lv
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jinhui Sun
- Gastroenterology Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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11
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Ahmad A, Ashfaq M, Rashid M. Editorial: The intricate web of gastrointestinal virome, mycome and archaeome: implications for gastrointestinal diseases. Front Genet 2024; 15:1463350. [PMID: 39184347 PMCID: PMC11341467 DOI: 10.3389/fgene.2024.1463350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 07/30/2024] [Indexed: 08/27/2024] Open
Affiliation(s)
- Asrar Ahmad
- Center for Sickle Cell Disease, Howard University, Washington, DC, United States
| | - Mohammad Ashfaq
- The University Centre for Research and Development (UCRD), Chandigarh University, Mohali, Punjab, India
| | - Mudasir Rashid
- Department of Medicine and Cancer Center, Howard University, Washington, DC, United States
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Baffy G, Portincasa P. Gut Microbiota and Sinusoidal Vasoregulation in MASLD: A Portal Perspective. Metabolites 2024; 14:324. [PMID: 38921459 PMCID: PMC11205793 DOI: 10.3390/metabo14060324] [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: 05/11/2024] [Revised: 05/30/2024] [Accepted: 06/06/2024] [Indexed: 06/27/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition with heterogeneous outcomes difficult to predict at the individual level. Feared complications of advanced MASLD are linked to clinically significant portal hypertension and are initiated by functional and mechanical changes in the unique sinusoidal capillary network of the liver. Early sinusoidal vasoregulatory changes in MASLD lead to increased intrahepatic vascular resistance and represent the beginning of portal hypertension. In addition, the composition and function of gut microbiota in MASLD are distinctly different from the healthy state, and multiple lines of evidence demonstrate the association of dysbiosis with these vasoregulatory changes. The gut microbiota is involved in the biotransformation of nutrients, production of de novo metabolites, release of microbial structural components, and impairment of the intestinal barrier with impact on innate immune responses, metabolism, inflammation, fibrosis, and vasoregulation in the liver and beyond. The gut-liver axis is a conceptual framework in which portal circulation is the primary connection between gut microbiota and the liver. Accordingly, biochemical and hemodynamic attributes of portal circulation may hold the key to better understanding and predicting disease progression in MASLD. However, many specific details remain hidden due to limited access to the portal circulation, indicating a major unmet need for the development of innovative diagnostic tools to analyze portal metabolites and explore their effect on health and disease. We also need to safely and reliably monitor portal hemodynamics with the goal of providing preventive and curative interventions in all stages of MASLD. Here, we review recent advances that link portal metabolomics to altered sinusoidal vasoregulation and may allow for new insights into the development of portal hypertension in MASLD.
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Affiliation(s)
- Gyorgy Baffy
- Section of Gastroenterology, Department of Medicine, VA Boston Healthcare System, Boston, MA 02130, USA
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Piero Portincasa
- Division of Internal Medicine, Department of Precision and Regenerative Medicine, University ‘Aldo Moro’ Medical School, 70121 Bari, Italy;
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13
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Conde‐Pérez K, Buetas E, Aja‐Macaya P, Martin‐De Arribas E, Iglesias‐Corrás I, Trigo‐Tasende N, Nasser‐Ali M, Estévez LS, Rumbo‐Feal S, Otero‐Alén B, Noguera JF, Concha Á, Pardiñas‐López S, Carda‐Diéguez M, Gómez‐Randulfe I, Martínez‐Lago N, Ladra S, Aparicio LA, Bou G, Mira A, Vallejo JA, Poza M. Parvimonas micra can translocate from the subgingival sulcus of the human oral cavity to colorectal adenocarcinoma. Mol Oncol 2024; 18:1143-1173. [PMID: 37558206 PMCID: PMC11076991 DOI: 10.1002/1878-0261.13506] [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: 03/02/2023] [Revised: 06/01/2023] [Accepted: 08/08/2023] [Indexed: 08/11/2023] Open
Abstract
Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non-CRC) were collected for microbiome analysis. Saliva (28 non-CRC and 94 CRC), feces (30 non-CRC and 97 CRC), subgingival fluid (20 CRC), and tumor tissue samples (20 CRC) were used for 16S metabarcoding and/or RNA sequencing (RNAseq) approaches. A differential analysis of the abundance, performed with the ANCOM-BC package, adjusting the P-values by the Holm-Bonferroni method, revealed that Parvimonas was significantly over-represented in feces from CRC patients (P-value < 0.001) compared to healthy controls. A total of 11 Parvimonas micra isolates were obtained from the oral cavity and adenocarcinoma of CRC patients. Genome analysis identified a pair of isolates from the same patient that shared 99.2% identity, demonstrating that P. micra can translocate from the subgingival cavity to the gut. The data suggest that P. micra could migrate in a synergistic consortium with other periodontal bacteria. Metatranscriptomics confirmed that oral bacteria were more active in tumor than in non-neoplastic tissues. We suggest that P. micra could be considered as a CRC biomarker detected in non-invasive samples such as feces.
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Affiliation(s)
- Kelly Conde‐Pérez
- meiGAbiome, Microbiology Research Group, Servicio de MicrobiologíaCenter for Advanced Scientific Research (CICA), Institute of Biomedical Research (INIBIC), University Hospital of A Coruña (HUAC), University of A Coruña (UDC), CIBER of Infectious Diseases (CIBERINFEC‐ISCIII), Hospital UniversitarioSpain
| | - Elena Buetas
- Genomic and Health DepartmentFISABIO Foundation, Center for Advanced Research in Public HealthValenciaSpain
| | - Pablo Aja‐Macaya
- meiGAbiome, Microbiology Research Group, Servicio de MicrobiologíaCenter for Advanced Scientific Research (CICA), Institute of Biomedical Research (INIBIC), University Hospital of A Coruña (HUAC), University of A Coruña (UDC), CIBER of Infectious Diseases (CIBERINFEC‐ISCIII), Hospital UniversitarioSpain
| | - Elsa Martin‐De Arribas
- Database LaboratoryResearch Center for Information and Communication Technologies (CITIC), University of A Coruña (UDC), Campus de ElviñaSpain
| | - Iago Iglesias‐Corrás
- Database LaboratoryResearch Center for Information and Communication Technologies (CITIC), University of A Coruña (UDC), Campus de ElviñaSpain
| | - Noelia Trigo‐Tasende
- meiGAbiome, Microbiology Research Group, Servicio de MicrobiologíaCenter for Advanced Scientific Research (CICA), Institute of Biomedical Research (INIBIC), University Hospital of A Coruña (HUAC), University of A Coruña (UDC), CIBER of Infectious Diseases (CIBERINFEC‐ISCIII), Hospital UniversitarioSpain
| | - Mohammed Nasser‐Ali
- meiGAbiome, Microbiology Research Group, Servicio de MicrobiologíaCenter for Advanced Scientific Research (CICA), Institute of Biomedical Research (INIBIC), University Hospital of A Coruña (HUAC), University of A Coruña (UDC), CIBER of Infectious Diseases (CIBERINFEC‐ISCIII), Hospital UniversitarioSpain
| | - Lara S. Estévez
- Pathological Anatomy Service and BiobankUniversity Hospital of A Coruña (HUAC), Institute of Biomedical Research (INIBIC), Hospital UniversitarioSpain
| | - Soraya Rumbo‐Feal
- meiGAbiome, Microbiology Research Group, Servicio de MicrobiologíaCenter for Advanced Scientific Research (CICA), Institute of Biomedical Research (INIBIC), University Hospital of A Coruña (HUAC), University of A Coruña (UDC), CIBER of Infectious Diseases (CIBERINFEC‐ISCIII), Hospital UniversitarioSpain
| | - Begoña Otero‐Alén
- Pathological Anatomy Service and BiobankUniversity Hospital of A Coruña (HUAC), Institute of Biomedical Research (INIBIC), Hospital UniversitarioSpain
| | - Jose F. Noguera
- General and Digestive Surgery ServiceUniversity Hospital of A Coruña (HUAC), Hospital UniversitarioSpain
| | - Ángel Concha
- Pathological Anatomy Service and BiobankUniversity Hospital of A Coruña (HUAC), Institute of Biomedical Research (INIBIC), Hospital UniversitarioSpain
| | - Simón Pardiñas‐López
- Periodontology and Oral SurgeryPardiñas Medical Dental Clinic, Cell Therapy and Regenerative Medicine Group, Institute of Biomedical Research (INIBIC)A CoruñaSpain
| | - Miguel Carda‐Diéguez
- Genomic and Health DepartmentFISABIO Foundation, Center for Advanced Research in Public HealthValenciaSpain
| | - Igor Gómez‐Randulfe
- Medical Oncology DepartmentUniversity Hospital of A Coruña (HUAC), Maternal and Child HospitalSpain
| | - Nieves Martínez‐Lago
- Medical Oncology DepartmentUniversity Hospital of A Coruña (HUAC), Maternal and Child HospitalSpain
| | - Susana Ladra
- Database LaboratoryResearch Center for Information and Communication Technologies (CITIC), University of A Coruña (UDC), Campus de ElviñaSpain
| | - Luis A. Aparicio
- Medical Oncology DepartmentUniversity Hospital of A Coruña (HUAC), Maternal and Child HospitalSpain
| | - Germán Bou
- meiGAbiome, Microbiology Research Group, Servicio de MicrobiologíaCenter for Advanced Scientific Research (CICA), Institute of Biomedical Research (INIBIC), University Hospital of A Coruña (HUAC), University of A Coruña (UDC), CIBER of Infectious Diseases (CIBERINFEC‐ISCIII), Hospital UniversitarioSpain
| | - Alex Mira
- Genomic and Health DepartmentFISABIO Foundation, Center for Advanced Research in Public HealthValenciaSpain
| | - Juan A. Vallejo
- meiGAbiome, Microbiology Research Group, Servicio de MicrobiologíaCenter for Advanced Scientific Research (CICA), Institute of Biomedical Research (INIBIC), University Hospital of A Coruña (HUAC), University of A Coruña (UDC), CIBER of Infectious Diseases (CIBERINFEC‐ISCIII), Hospital UniversitarioSpain
| | - Margarita Poza
- meiGAbiome, Microbiology Research Group, Servicio de MicrobiologíaCenter for Advanced Scientific Research (CICA), Institute of Biomedical Research (INIBIC), University Hospital of A Coruña (HUAC), University of A Coruña (UDC), CIBER of Infectious Diseases (CIBERINFEC‐ISCIII), Hospital UniversitarioSpain
- Microbiome and Health Group, Faculty of SciencesUniversity of A Coruña (UDC), Campus da ZapateiraSpain
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14
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Ansari M, Darvishi A. A review of the current state of natural biomaterials in wound healing applications. Front Bioeng Biotechnol 2024; 12:1309541. [PMID: 38600945 PMCID: PMC11004490 DOI: 10.3389/fbioe.2024.1309541] [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: 10/08/2023] [Accepted: 03/18/2024] [Indexed: 04/12/2024] Open
Abstract
Skin, the largest biological organ, consists of three main parts: the epidermis, dermis, and subcutaneous tissue. Wounds are abnormal wounds in various forms, such as lacerations, burns, chronic wounds, diabetic wounds, acute wounds, and fractures. The wound healing process is dynamic, complex, and lengthy in four stages involving cells, macrophages, and growth factors. Wound dressing refers to a substance that covers the surface of a wound to prevent infection and secondary damage. Biomaterials applied in wound management have advanced significantly. Natural biomaterials are increasingly used due to their advantages including biomimicry of ECM, convenient accessibility, and involvement in native wound healing. However, there are still limitations such as low mechanical properties and expensive extraction methods. Therefore, their combination with synthetic biomaterials and/or adding bioactive agents has become an option for researchers in this field. In the present study, the stages of natural wound healing and the effect of biomaterials on its direction, type, and level will be investigated. Then, different types of polysaccharides and proteins were selected as desirable natural biomaterials, polymers as synthetic biomaterials with variable and suitable properties, and bioactive agents as effective additives. In the following, the structure of selected biomaterials, their extraction and production methods, their participation in wound healing, and quality control techniques of biomaterials-based wound dressings will be discussed.
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Affiliation(s)
- Mojtaba Ansari
- Department of Biomedical Engineering, Meybod University, Meybod, Iran
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15
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Jiang H, Li R, Zhao M, Peng X, Sun M, Liu C, Liu G, Xue H. Toxic effects of combined exposure to cadmium and diclofenac on freshwater crayfish (Procambarus clarkii): Insights from antioxidant enzyme activity, histopathology, and gut microbiome. AQUATIC TOXICOLOGY (AMSTERDAM, NETHERLANDS) 2024; 268:106844. [PMID: 38295602 DOI: 10.1016/j.aquatox.2024.106844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 12/20/2023] [Accepted: 01/21/2024] [Indexed: 02/02/2024]
Abstract
In recent years, excessive discharge of pollutants has led to increasing concentrations of cadmium (Cd) and diclofenac (DCF) in water; however, the toxicity mechanism of combined exposure of the two pollutants to aquatic animals has not been fully studied. Procambarus clarkii is an economically important aquatic species that is easily affected by Cd and DCF. This study examined the effects of combined exposure to Cd and DCF on the tissue accumulation, physiology, biochemistry, and gut microflora of P. clarkii. The results showed that Cd and DCF accumulated in tissues in the order of hepatopancreas > gill > intestine > muscle. The hepatopancreas and intestines were subjected to severe oxidative stress, with significantly increased antioxidant enzyme activity. Pathological examination revealed lumen expansion and epithelial vacuolisation in the hepatopancreas and damage to the villous capillaries and wall in the intestine. The co-exposure to Cadmium (Cd) and Diclofenac (DCF) disrupts the Firmicutes/Bacteroidetes (F/B) ratio, impairing the regular functioning of intestinal microbiota in carbon (C) and nitrogen (N) cycling. This disturbance consequently hinders the absorption and utilization of energy and nutrients in Procambarus clarkii. This study offers critical insights into the toxicological mechanisms underlying the combined effects of Cd and DCF, and suggests potential approaches to alleviate their adverse impacts on aquatic ecosystems.
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Affiliation(s)
- Hucheng Jiang
- Freshwater Fisheries Research Institute of Jiangsu Province, Nanjing, 210017, China; The Low-temperature Germplasm Bank of Important Economic Fish (Freshwater Fisheries Research Institute of Jiangsu Province) of Jiangsu Provincial Science and Technology Resources (Agricultural Germplasm Resources) Coordination Service Platform, Nanjing, 210017, China
| | - Runbo Li
- Key Laboratory of Freshwater Aquatic Genetic Resources Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai, 201306, China
| | - Muzi Zhao
- Freshwater Fisheries Research Institute of Jiangsu Province, Nanjing, 210017, China; The Low-temperature Germplasm Bank of Important Economic Fish (Freshwater Fisheries Research Institute of Jiangsu Province) of Jiangsu Provincial Science and Technology Resources (Agricultural Germplasm Resources) Coordination Service Platform, Nanjing, 210017, China
| | - Xinran Peng
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China
| | - Mengling Sun
- Freshwater Fisheries Research Institute of Jiangsu Province, Nanjing, 210017, China
| | - Chongwan Liu
- Freshwater Fisheries Research Institute of Jiangsu Province, Nanjing, 210017, China
| | - Guoxing Liu
- Freshwater Fisheries Research Institute of Jiangsu Province, Nanjing, 210017, China; The Low-temperature Germplasm Bank of Important Economic Fish (Freshwater Fisheries Research Institute of Jiangsu Province) of Jiangsu Provincial Science and Technology Resources (Agricultural Germplasm Resources) Coordination Service Platform, Nanjing, 210017, China
| | - Hui Xue
- Freshwater Fisheries Research Institute of Jiangsu Province, Nanjing, 210017, China; The Low-temperature Germplasm Bank of Important Economic Fish (Freshwater Fisheries Research Institute of Jiangsu Province) of Jiangsu Provincial Science and Technology Resources (Agricultural Germplasm Resources) Coordination Service Platform, Nanjing, 210017, China.
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16
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Tong M, Yang X, Qiao Y, Liu G, Ge H, Huang G, Wang Y, Yang Y, Fan W. Serine protease inhibitor from the muscle larval Trichinella spiralis ameliorates non-alcoholic fatty liver disease in mice via anti-inflammatory properties and gut-liver crosstalk. Biomed Pharmacother 2024; 172:116223. [PMID: 38325266 DOI: 10.1016/j.biopha.2024.116223] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 01/22/2024] [Accepted: 01/29/2024] [Indexed: 02/09/2024] Open
Abstract
Trichinella spiralis is recognized for its ability to regulate host immune responses. The serine protease inhibitor of T. spiralis (Ts-SPI) participates in T. spiralis-mediated immunoregulatory effects. Studies have shown that helminth therapy exhibits therapeutic effects on metabolic diseases. In addition, we previously found that T. spiralis-derived crude antigens could alleviate diet-induced obesity. Thus, Ts-SPI was hypothesized to alleviate non-alcoholic fatty liver disease (NAFLD). Herein, recombinant Ts-SPI (rTs-SPI) was prepared from the muscle larvae T. spiralis. The relative molecular mass of rTs-SPI was approximately 35,000 Da, and western blot analysis indicated good immunoreactivity. rTs-SPI ameliorated hepatic steatosis, inflammation, and pyroptosis in NAFLD mice, which validated the hypothesis. rTs-SPI also reduced macrophage infiltration, significantly expanded Foxp3+ Treg population, and inactivated TLR4/NF-κB/NLRP3 signaling in the liver. Furthermore, rTs-SPI treatment significantly shifted the gut microbiome structure, with a remarkable increase in beneficial bacteria and reduction in harmful bacteria to improve gut barrier integrity. Finally, Abx-treated mice and FMT confirmed that gut-liver crosstalk contributed to NAFLD improvement after rTs-SPI treatment. Taken together, Taken together, these findings suggest that rTs-SPI exerts therapeutic effects in NAFLD via anti-inflammatory activity and gut-liver crosstalk.
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Affiliation(s)
- Mingwei Tong
- School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, China; Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and Shanxi Key Laboratory of Cellular Physiology, Taiyuan 030001, China.
| | - Xiaodan Yang
- School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, China
| | - Yuyu Qiao
- School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, China
| | - Ge Liu
- School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, China
| | - Huihui Ge
- School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, China
| | - Guangrong Huang
- School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, China
| | - Yanhong Wang
- School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, China; Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and Shanxi Key Laboratory of Cellular Physiology, Taiyuan 030001, China
| | - Yong Yang
- School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, China; Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and Shanxi Key Laboratory of Cellular Physiology, Taiyuan 030001, China.
| | - Weiping Fan
- School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, China; Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and Shanxi Key Laboratory of Cellular Physiology, Taiyuan 030001, China.
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17
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Narayanan V, Devadas K, Sreesh S, Varghese J, Solanki R, Mohapatra SD, Pal R, Madhu D, Chakravorty A. Novel predictors of response to therapy with terlipressin and albumin in hepatorenal syndrome-acute kidney injury. Ann Gastroenterol 2024; 37:81-88. [PMID: 38223250 PMCID: PMC10785019 DOI: 10.20524/aog.2023.0853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 11/27/2023] [Indexed: 01/16/2024] Open
Abstract
Background A combination of terlipressin and albumin is the first-line pharmacologic treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI). We assessed the response rates to terlipressin-albumin therapy in patients with HRS-AKI and determined early predictors of treatment response and survival. Methods A total of 84 patients with HRS-AKI (International Club of Ascites definition 2015) treated with terlipressin-albumin were included. Predictors of HRS reversal were identified by logistic regression analysis. Survival analysis was performed using the Kaplan-Meier method, and Cox regression models were used to determine independent predictors of mortality. Results Complete response to therapy was observed in 54.8%, partial response in 14.3%, and no response in 31% of patients. The factors associated with complete treatment response were the presence of systemic inflammatory response syndrome (SIRS), baseline serum creatinine, a rise in mean arterial pressure by day 3, and a reduction in the renal resistive index (ΔRRI) by day 3 of treatment. Independent predictors of HRS reversal were the presence of SIRS at baseline (P=0.022; odds ratio [OR] 15.74, 95% confidence interval [CI] 1.47-167.82) and ΔRRI ≥5% by day 3 of treatment (P=0.048; OR 6.67, 95%CI 1.021-43.62). Mean transplant-free survival at 6 months was significantly better in treatment responders (148 vs. 90 days, P<0.001). Independent predictors of 6-month mortality were response to treatment (P=0.004) and model for end-stage liver disease-sodium >23 (P=0.018). Conclusions SIRS and ΔRRI are simple parameters to predict treatment response in HRS-AKI. Non-responders have higher mortality and should be identified early to expedite liver transplantation.
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Affiliation(s)
- Vijay Narayanan
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Krishnadas Devadas
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Srijaya Sreesh
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Jijo Varghese
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Rushil Solanki
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Shivabrata Dhal Mohapatra
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Ravindra Pal
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Devika Madhu
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
| | - Avisek Chakravorty
- Department of Medical Gastroenterology, Government Medical College, Thiruvananthapuram, Kerala, India (Vijay Narayanan, Krishnadas Devadas, Srijaya Sreesh, Jijo Varghese, Rushil Solanki, Shivabrata Dhal Mohapatra, Ravindra Pal, Devika Madhu, Avisek Chakravorty)
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18
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Menżyk T, Skladany L, Adamcova-Selcanova S, Vnencakova J, Zilincanova D, Bystrianska N, Hudy D, Skonieczna M, Marlicz W, Kukla M. Concomitant diverticulosis among patients undergoing liver transplantation. Does it influence the length of hospitalization after the procedure? Clin Exp Hepatol 2023; 9:344-350. [PMID: 38774193 PMCID: PMC11103805 DOI: 10.5114/ceh.2023.132255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 08/19/2023] [Indexed: 05/24/2024] Open
Abstract
Aim of the study We tried to assess the influence of concomitant diverticulosis and other factors, e.g., Child-Pugh (C-P) and MELD scores, viral etiology, and presence of alcoholic disease, on short-term results of liver transplantation (LT) with an emphasis on duration of patient's hospitalization. Material and methods This prospective study was performed on 206 cirrhotic patients who were selected for LT. In order to assess the presence of diverticculosis we performed colonoscopy. Results The duration of hospitalization after LT did not differ significantly between patients with and without diverticulosis (27.5 [21.0-33.5] vs. 24.0 [18.0-32.0] days, p = 0.28). Patients with C-P class C were hospitalized longer in comparison to the class B patients. It is reflected in the positive correlation between C-P score and days of hospitalization (r = 0.22, p = 0.002). Patients with diverticulosis were significantly older (59.6 [51.1-63.3] vs. 52.9 [43.8-59.2] years, p = 0.03). Alcoholic liver disease (ALD) was associated with a greater risk of diverticulosis (OR = 3.89, 95% CI [1.13-15.87], p = 0.04). Conclusions Presence of diverticulosis among subjects undergoing LT did not influence the duration of hospitalization after the procedure. Significantly longer hospitalization was observed in patients with the most advanced liver disease according to C-P score. To determine the exact impact of diverticulosis on short-term results of LT additional studies are required.
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Affiliation(s)
- Tomasz Menżyk
- Department of Internal Medicine, Gastroenterology and Hematology, St. Lucas Hospital, Tarnów, Poland
| | - Lubomir Skladany
- Department of Internal Medicine and HEGITO (Hepatology, Gastroenterology and Liver Transplantation), F.D. Roosevelt University Hospital, Banska Bystrica, Slovakia
- Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia
| | - Svetlana Adamcova-Selcanova
- Department of Internal Medicine and HEGITO (Hepatology, Gastroenterology and Liver Transplantation), F.D. Roosevelt University Hospital, Banska Bystrica, Slovakia
| | - Janka Vnencakova
- Department of Internal Medicine and HEGITO (Hepatology, Gastroenterology and Liver Transplantation), F.D. Roosevelt University Hospital, Banska Bystrica, Slovakia
| | - Daniela Zilincanova
- Department of Internal Medicine and HEGITO (Hepatology, Gastroenterology and Liver Transplantation), F.D. Roosevelt University Hospital, Banska Bystrica, Slovakia
| | - Natalia Bystrianska
- Department of Internal Medicine and HEGITO (Hepatology, Gastroenterology and Liver Transplantation), F.D. Roosevelt University Hospital, Banska Bystrica, Slovakia
| | - Dorota Hudy
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Magdalena Skonieczna
- Department of Systems Biology and Engineering, Silesian University of Technology, Gliwice, Poland
- Biotechnology Centre, Silesian University of Technology, Gliwice, Poland
| | - Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland
| | - Michał Kukla
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
- Department of Endoscopy, University Hospital, Cracow, Poland
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19
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Maslennikov R, Poluektova E, Zolnikova O, Sedova A, Kurbatova A, Shulpekova Y, Dzhakhaya N, Kardasheva S, Nadinskaia M, Bueverova E, Nechaev V, Karchevskaya A, Ivashkin V. Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis. Int J Mol Sci 2023; 24:16502. [PMID: 38003692 PMCID: PMC10671141 DOI: 10.3390/ijms242216502] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/11/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open
Abstract
Cirrhosis is the end result of liver fibrosis in chronic liver diseases. Studying the mechanisms of its development and developing measures to slow down and regress it based on this knowledge seem to be important tasks for medicine. Currently, disorders of the gut-liver axis have great importance in the pathogenesis of cirrhosis. However, gut dysbiosis, which manifests as increased proportions in the gut microbiota of Bacilli and Proteobacteria that are capable of bacterial translocation and a decreased proportion of Clostridia that strengthen the intestinal barrier, occurs even at the pre-cirrhotic stage of chronic liver disease. This leads to the development of bacterial translocation, a process by which those microbes enter the blood of the portal vein and then the liver tissue, where they activate Kupffer cells through Toll-like receptor 4. In response, the Kupffer cells produce profibrogenic cytokines, which activate hepatic stellate cells, stimulating their transformation into myofibroblasts that produce collagen and other elements of the extracellular matrix. Blocking bacterial translocation with antibiotics, probiotics, synbiotics, and other methods could slow down the progression of liver fibrosis. This was shown in a number of animal models but requires further verification in long-term randomized controlled trials with humans.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119048 Moscow, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119048 Moscow, Russia
| | - Oxana Zolnikova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Alla Sedova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Anastasia Kurbatova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Yulia Shulpekova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Natyia Dzhakhaya
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Svetlana Kardasheva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Maria Nadinskaia
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Elena Bueverova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Vladimir Nechaev
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Anna Karchevskaya
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119048 Moscow, Russia (A.S.); (N.D.); (M.N.); (E.B.)
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119048 Moscow, Russia
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20
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Torre A, Cisneros-Garza LE, Castillo-Barradas M, Navarro-Alvarez N, Sandoval-Salas R, González-Huezo MS, Pérez-Hernández JL, Méndez-Guerrero O, Ruiz-Manríquez JA, Trejo-Estrada R, Chavez-Tapia NC, Solís-Gasca LC, Moctezuma-Velázquez C, Aguirre-Valádez J, Flores-Calderón J, Higuera-de-la-Tijera F, García-Juárez I, Canedo-Castillo NA, Malé-Velázquez R, Montalvo-Gordon I, Vilatobá M, Márquez-Guillén E, Córdova-Gallardo J, Flores-García NC, Miranda-Zazueta G, Martínez-Saldívar BI, Páez-Zayas VM, Muñoz-Espinosa LE, Solís-Galindo FA. Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology. Ann Hepatol 2023; 28:101140. [PMID: 37482299 DOI: 10.1016/j.aohep.2023.101140] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/26/2023] [Accepted: 05/31/2023] [Indexed: 07/25/2023]
Abstract
Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.
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Affiliation(s)
- Aldo Torre
- Metabolic Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
| | - Laura Esthela Cisneros-Garza
- Gastroenterology and Hepatology Department, Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico
| | | | - Nalu Navarro-Alvarez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Osvely Méndez-Guerrero
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Luis Carlos Solís-Gasca
- Gastroenterology Department, Hospital General de Zona #12 Benito Juárez del Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico
| | - Carlos Moctezuma-Velázquez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Medicine - Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | | | - Judith Flores-Calderón
- Pediatrics Department, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | | | - Ignacio García-Juárez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Iaarah Montalvo-Gordon
- Clinic of Gastrointestinal and Hepatic Specialties, Hospital Faro del Mayab, Mérida, Yucatán, Mexico
| | - Mario Vilatobá
- Transplant Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Ernesto Márquez-Guillén
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Hospital Ángeles del Pedregal, Mexico City, Mexico
| | - Jacqueline Córdova-Gallardo
- Hepatology Department - General Surgery Service, Hospital General Dr. Manuel Gea González, Mexico City, Mexico
| | - Nayeli Cointa Flores-García
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Godolfino Miranda-Zazueta
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Linda Elsa Muñoz-Espinosa
- Universidad Autónoma de Nuevo León. Liver Unit, Department of Internal Medicine, University Hospital 'Dr. José E. González', Monterrey, Nuevo León, Mexico
| | - Francisco Alfonso Solís-Galindo
- Gastroenterology Department, Unidad Médica de Alta Especialidad # 71 Instituto Mexicano del Seguro Social, Torreón, Coahuila, Mexico
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21
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Magdy Wasfy R, Mbaye B, Borentain P, Tidjani Alou M, Murillo Ruiz ML, Caputo A, Andrieu C, Armstrong N, Million M, Gerolami R. Ethanol-Producing Enterocloster bolteae Is Enriched in Chronic Hepatitis B-Associated Gut Dysbiosis: A Case-Control Culturomics Study. Microorganisms 2023; 11:2437. [PMID: 37894093 PMCID: PMC10608849 DOI: 10.3390/microorganisms11102437] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 09/25/2023] [Accepted: 09/26/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a global health epidemic that causes fatal complications, leading to liver cirrhosis and hepatocellular carcinoma. The link between HBV-related dysbiosis and specific bacterial taxa is still under investigation. Enterocloster is emerging as a new genus (formerly Clostridium), including Enterocloster bolteae, a gut pathogen previously associated with dysbiosis and human diseases such as autism, multiple sclerosis, and inflammatory bowel diseases. Its role in liver diseases, especially HBV infection, is not reported. METHODS The fecal samples of eight patients with chronic HBV infection and ten healthy individuals were analyzed using the high-throughput culturomics approach and compared to 16S rRNA sequencing. Quantification of ethanol, known for its damaging effect on the liver, produced from bacterial strains enriched in chronic HBV was carried out by gas chromatography-mass spectrometry. RESULTS Using culturomics, 29,120 isolated colonies were analyzed by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-TOF); 340 species were identified (240 species in chronic HBV samples, 254 species in control samples) belonging to 169 genera and 6 phyla. In the chronic HBV group, 65 species were already known in the literature; 48 were associated with humans but had not been previously found in the gut, and 17 had never been associated with humans previously. Six species were newly isolated in our study. By comparing bacterial species frequency, three bacterial genera were serendipitously found with significantly enriched bacterial diversity in patients with chronic HBV: Enterocloster, Clostridium, and Streptococcus (p = 0.0016, p = 0.041, p = 0.053, respectively). However, metagenomics could not identify this enrichment, possibly concerning its insufficient taxonomical resolution (equivocal assignment of operational taxonomic units). At the species level, the significantly enriched species in the chronic HBV group almost all belonged to class Clostridia, such as Clostridium perfringens, Clostridium sporogenes, Enterocloster aldenensis, Enterocloster bolteae, Enterocloster clostridioformis, and Clostridium innocuum. Two E. bolteae strains, isolated from two patients with chronic HBV infection, showed high ethanol production (27 and 200 mM). CONCLUSIONS Culturomics allowed us to identify Enterocloster species, specifically, E. bolteae, enriched in the gut microbiota of patients with chronic HBV. These species had never been isolated in chronic HBV infection before. Moreover, ethanol production by E. bolteae strains isolated from the chronic HBV group could contribute to liver disease progression. Additionally, culturomics might be critical for better elucidating the relationship between dysbiosis and chronic HBV infection in the future.
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Affiliation(s)
- Reham Magdy Wasfy
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
| | - Babacar Mbaye
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
| | - Patrick Borentain
- Unité Hépatologie, Hôpital de la Timone, APHM, 13005 Marseille, France;
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
| | - Maryam Tidjani Alou
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
| | - Maria Leticia Murillo Ruiz
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
| | - Aurelia Caputo
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
| | - Claudia Andrieu
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
| | - Nicholas Armstrong
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
| | - Matthieu Million
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
| | - Rene Gerolami
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
- Unité Hépatologie, Hôpital de la Timone, APHM, 13005 Marseille, France;
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
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Qi Z, Qi X, Xu Y, Sun H, Li D, Liu J, Cong M, Liu T. Alterations in the "Gut-Liver Axis" on Rats with Immunological Hepatic Fibrosis. J Immunol Res 2023; 2023:5577850. [PMID: 37781475 PMCID: PMC10539088 DOI: 10.1155/2023/5577850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 08/25/2023] [Accepted: 08/28/2023] [Indexed: 10/03/2023] Open
Abstract
There remains a lack of standard models that have all the characteristics of human diseases. Especially in immunological hepatic fibrosis, the bovine serum albumin (BSA)-induced liver fibrosis models have the same developmental mechanisms as human liver fibrosis models, but have received little attention. We standardized a BSA-induced liver fibrosis model in rats and thoroughly assessed its pathological characteristics. We also used 16S sequencing to assess homeostasis of the intestinal microflora of rats with BSA-induced liver fibrosis and detected various differential metabolites in the serum of these rats using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). We observed stable and unambiguous histological changes in liver tissue morphology and remarkably high concentrations of inflammatory markers in the serum of BSA-induced liver fibrosis rats. In keeping with the fact that BSA induction can cause gut microbiota disorders in rats. UHPLC-MS/MS analysis of rat serum samples in positive-ion mode and negative-ion mode revealed 17 and 25 differential metabolites, respectively. Network analysis revealed that phenylalanine or tyrosine metabolites (e.g., PAGln) were the predominant metabolites in the sera of BSA-induced liver fibrosis rats. Taken together, our results suggest that disorders of amino acid metabolism caused by the gut microbiota may play an important role in the progression of immunological hepatic fibrosis.
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Affiliation(s)
- Zhaoyao Qi
- School of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi 830011, Xinjiang Uyghur Autonomous Region, China
| | - Xinxin Qi
- School of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi 830011, Xinjiang Uyghur Autonomous Region, China
| | - Yuanhui Xu
- School of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi 830011, Xinjiang Uyghur Autonomous Region, China
| | - Hongguang Sun
- School of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi 830011, Xinjiang Uyghur Autonomous Region, China
| | - Dengfeng Li
- School of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi 830011, Xinjiang Uyghur Autonomous Region, China
| | - Jincun Liu
- School of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi 830011, Xinjiang Uyghur Autonomous Region, China
| | - Meili Cong
- School of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi 830011, Xinjiang Uyghur Autonomous Region, China
| | - Tao Liu
- School of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi 830011, Xinjiang Uyghur Autonomous Region, China
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23
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Maslennikov R, Alieva A, Poluektova E, Zharikov Y, Suslov A, Letyagina Y, Vasileva E, Levshina A, Kozlov E, Ivashkin V. Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota. World J Gastroenterol 2023; 29:4236-4251. [PMID: 37545638 PMCID: PMC10401661 DOI: 10.3748/wjg.v29.i27.4236] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/25/2023] [Accepted: 06/21/2023] [Indexed: 07/13/2023] Open
Abstract
Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Aliya Alieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Yury Zharikov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Andrey Suslov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Yana Letyagina
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Ekaterina Vasileva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Anna Levshina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Evgenii Kozlov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
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Rodríguez-Lara A, Rueda-Robles A, Sáez-Lara MJ, Plaza-Diaz J, Álvarez-Mercado AI. From Non-Alcoholic Fatty Liver Disease to Liver Cancer: Microbiota and Inflammation as Key Players. Pathogens 2023; 12:940. [PMID: 37513787 PMCID: PMC10385788 DOI: 10.3390/pathogens12070940] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/12/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open
Abstract
It is estimated that 25% of the world's population has non-alcoholic fatty liver disease. This disease can advance to a more severe form, non-alcoholic steatohepatitis (NASH), a disease with a greater probability of progression to cirrhosis and hepatocellular carcinoma (HCC). NASH could be characterized as a necro-inflammatory complication of chronic hepatic steatosis. The combination of factors that lead to NASH and its progression to HCC in the setting of inflammation is not clearly understood. The portal vein is the main route of communication between the intestine and the liver. This allows the transfer of products derived from the intestine to the liver and the hepatic response pathway of bile and antibody secretion to the intestine. The intestinal microbiota performs a fundamental role in the regulation of immune function, but it can undergo changes that alter its functionality. These changes can also contribute to cancer by disrupting the immune system and causing chronic inflammation and immune dysfunction, both of which are implicated in cancer development. In this article, we address the link between inflammation, microbiota and HCC. We also review the different in vitro models, as well as recent clinical trials addressing liver cancer and microbiota.
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Affiliation(s)
- Avilene Rodríguez-Lara
- Center of Biomedical Research, Institute of Nutrition and Food Technology “José Mataix”, University of Granada, Avda. del Conocimiento s/n., Armilla, 18016 Granada, Spain;
| | - Ascensión Rueda-Robles
- Department of Nutrition and Food Science, Faculty of Pharmacy, University of Granada,18071 Granada, Spain;
| | - María José Sáez-Lara
- Department of Biochemistry and Molecular Biology I, School of Sciences, University of Granada, 18071 Granada, Spain;
| | - Julio Plaza-Diaz
- Children’s Hospital Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada
- Instituto de Investigación Biosanitaria ibs.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain
| | - Ana I. Álvarez-Mercado
- Center of Biomedical Research, Institute of Nutrition and Food Technology “José Mataix”, University of Granada, Avda. del Conocimiento s/n., Armilla, 18016 Granada, Spain;
- Instituto de Investigación Biosanitaria ibs.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain
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25
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Catalano T, Selvaggi F, Esposito DL, Cotellese R, Aceto GM. Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers. Microorganisms 2023; 11:1632. [PMID: 37512809 PMCID: PMC10386003 DOI: 10.3390/microorganisms11071632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 06/18/2023] [Accepted: 06/20/2023] [Indexed: 07/30/2023] Open
Abstract
Interaction between infectious agents and liver tissue, as well as repeated and extreme biological events beyond adaptive capacities, may result in pathological conditions predisposing people to development of primary liver cancers (PLCs). In adults, PLCs mainly comprise hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Various infectious agents in the hepatic microenvironment can destabilize normal liver cell functions by modulating the Wnt/β-catenin pathway components. Among them, hepatotropic viruses B, C, and D are involved in Wnt/β-catenin signaling dysregulation. Other microbial agents, including oncogenic viruses such as Epstein-Barr virus (EBV) and human papilloma virus (HPV), bacteria, e.g., Mycoplasma hyorhinis and Salmonella Typhi, the protozoan parasite Toxoplasma gondii, the fungus Aspergillus flavus, and liver flukes such as Clonorchissinensis or Opisthorchis viverrini, may induce malignant transformation in hepatocytes or in target cells of the biliary tract through aberrant Wnt signaling activation. This review focuses on new insights into infectious agents implicated in the deregulation of Wnt signaling and PLC development. Since the Wnt/β-catenin pathway is a driver of cancer following viral and bacterial infections, molecules inhibiting the complex axis of Wnt signaling could represent novel therapeutic approaches in PLC treatment.
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Affiliation(s)
- Teresa Catalano
- Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
| | - Federico Selvaggi
- Unit of General Surgery, ASL2 Lanciano-Vasto-Chieti, Ospedale Clinicizzato SS Annunziata, 66100 Chieti, Italy;
| | - Diana Liberata Esposito
- Center for Advanced Studies and Technology (CAST), 66100 Chieti, Italy;
- Department of Innovative Technologies in Medicine & Dentistry, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
| | - Roberto Cotellese
- Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy;
- Villa Serena Foundation for Research, 65013 Città Sant’Angelo, Italy
| | - Gitana Maria Aceto
- Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy;
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26
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Hart B, Patel J, De Maayer P, Nweke EE, Bizos D. Metataxonomic Analysis Demonstrates a Shift in Duodenal Microbiota in Patients with Obstructive Jaundice. Microorganisms 2023; 11:1611. [PMID: 37375113 DOI: 10.3390/microorganisms11061611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/11/2023] [Accepted: 06/14/2023] [Indexed: 06/29/2023] Open
Abstract
The human gastrointestinal tract (GIT) is home to an abundance of diverse microorganisms, and the balance of this microbiome plays a vital role in maintaining a healthy GIT. The obstruction of the flow of bile into the duodenum, resulting in obstructive jaundice (OJ), has a major impact on the health of the affected individual. This study sought to identify changes in the duodenal microbiota in South African patients with OJ compared to those without this disorder. Mucosal biopsies were taken from the duodenum of nineteen jaundiced patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and nineteen control participants (non-jaundiced patients) undergoing gastroscopy. DNA extracted from the samples was subjected to 16S rRNA amplicon sequencing using the Ion S5 TM sequencing platform. Diversity metrics and statistical correlation analyses with the clinical data were performed to compare duodenal microbial communities in both groups. Differences in the mean distribution of the microbial communities in the jaundiced and non-jaundiced samples were observed; however, this difference did not reach statistical significance. Of note, there was a statistically significant difference between the mean distributions of bacteria comparing jaundiced patients with cholangitis to those without (p = 0.0026). On further subset analysis, a significant difference was observed between patients with benign (Cholelithiasis) and malignant disease, namely, head of pancreas (HOP) mass (p = 0.01). Beta diversity analyses further revealed a significant difference between patients with stone and non-stone related disease when factoring in the Campylobacter-Like Organisms (CLO) test status (p = 0.048). This study demonstrated a shift in the microbiota in jaundiced patients, especially considering some underlying conditions of the upper GI tract. Future studies should aim to verify these findings in a larger cohort.
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Affiliation(s)
- Benjamin Hart
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - Jasmin Patel
- School of Molecular and Cell Biology, Faculty of Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - Pieter De Maayer
- School of Molecular and Cell Biology, Faculty of Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - Ekene Emmanuel Nweke
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - Damon Bizos
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
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Kang Y, Kuang X, Yan H, Ren P, Yang X, Liu H, Liu Q, Yang H, Kang X, Shen X, Tong M, Li L, Wang X, Guo L, Ma J, Zhang F, Fan W. A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway. mSystems 2023; 8:e0112722. [PMID: 36794950 PMCID: PMC10134874 DOI: 10.1128/msystems.01127-22] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 01/18/2023] [Indexed: 02/17/2023] Open
Abstract
Autoimmune hepatitis (AIH) is a liver disease characterized by chronic liver inflammation. The intestinal barrier and microbiome play critical roles in AIH progression. AIH treatment remains challenging because first-line drugs have limited efficacy and many side effects. Thus, there is growing interest in developing synbiotic therapies. This study investigated the effects of a novel synbiotic in an AIH mouse model. We found that this synbiotic (Syn) ameliorated liver injury and improved liver function by reducing hepatic inflammation and pyroptosis. The Syn reversed gut dysbiosis, as indicated by an increase in beneficial bacteria (e.g., Rikenella and Alistipes) and a decrease in potentially harmful bacteria (e.g., Escherichia-Shigella) and lipopolysaccharide (LPS)-bearing Gram-negative bacterial levels. The Syn maintained intestinal barrier integrity, reduced LPS, and inhibited the TLR4/NF-κB and NLRP3/Caspase-1 signaling pathway. In addition, microbiome phenotype prediction by BugBase and bacterial functional potential prediction using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed that Syn improved gut microbiota function involving inflammatory injury, metabolism, immune response, and pathopoiesia. Furthermore, the new Syn was as effective as prednisone against AIH. Therefore, this novel Syn could be a candidate drug for alleviating AIH through its anti-inflammatory and antipyroptosis properties that relieve endothelial dysfunction and gut dysbiosis. IMPORTANCE Synbiotics can ameliorate liver injury and improve liver function by reducing hepatic inflammation and pyroptosis. Our data indicate that our new Syn not only reverses gut dysbiosis by increasing beneficial bacteria and decreasing lipopolysaccharide (LPS)-bearing Gram-negative bacteria but also maintains intestinal barrier integrity. Thus, its mechanism might be associated with modulating gut microbiota composition and intestinal barrier function by inhibiting the TLR4/NF-κB/NLRP3/pyroptosis signaling pathway in the liver. This Syn is as effective as prednisone in treating AIH without side effects. Based on these findings, this novel Syn represents a potential therapeutic agent for AIH in clinical practice.
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Affiliation(s)
- Yongbo Kang
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiaoyu Kuang
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Huan Yan
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Peng Ren
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiaodan Yang
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Haixia Liu
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Qingqing Liu
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Hao Yang
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xing Kang
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiaorong Shen
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Mingwei Tong
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Lin Li
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiaohui Wang
- Laboratory of Morphology, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Linzhi Guo
- Laboratory of Morphology, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jieqiong Ma
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Fan Zhang
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Weiping Fan
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China
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Efremova I, Maslennikov R, Alieva A, Poluektova E, Ivashkin V. Small Intestinal Bacterial Overgrowth Is Associated with Poor Prognosis in Cirrhosis. Microorganisms 2023; 11:1017. [PMID: 37110440 PMCID: PMC10143588 DOI: 10.3390/microorganisms11041017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/03/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Small intestinal bacterial overgrowth (SIBO) is associated with numerous manifestations of cirrhosis. To determine whether the presence of SIBO affects the prognosis in cirrhosis was the aim of the study. METHODS This prospective cohort study included 50 patients. All participants underwent a lactulose hydrogen breath test for SIBO. The follow-up period was 4 years. RESULTS SIBO was detected in 26 (52.0%) patients: in 10 (52.6%) patients with compensated cirrhosis and in 16 (51.6%) ones with decompensated cirrhosis. Twelve (46.2%) patients with SIBO and four (16.7%) patients without SIBO died within 4 years (p = 0.009). Among patients with decompensated cirrhosis, 8 (50.0%) patients with SIBO and 3 (20.0%) patients without SIBO died (p = 0.027). Among patients with compensated cirrhosis, four (40.0%) patients with SIBO and one (11.1%) patient without SIBO died (p = 0.045). Among patients with SIBO, there was no difference in mortality between patients with compensated and decompensated cirrhosis (p = 0.209). It was the same for patients without SIBO (p = 0.215). SIBO affects the prognosis only in the first year of follow-up in decompensated cirrhosis, and only in subsequent years in compensated cirrhosis. Presence of SIBO (p = 0.028; HR = 4.2(1.2-14.9)) and serum albumin level (p = 0.027) were significant independent risk factors for death in cirrhosis. CONCLUSIONS SIBO is associated with poor prognosis in cirrhosis.
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Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119121 Moscow, Russia
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119121 Moscow, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119121 Moscow, Russia
| | - Aliya Alieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119121 Moscow, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119121 Moscow, Russia
- The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, 119121 Moscow, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, 119121 Moscow, Russia
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Wei L, Zhang L, Zhang Y, Yan L, Liu B, Cao Z, Zhao N, He X, Li L, Lu C. Intestinal Escherichia coli and related dysfunction as potential targets of Traditional Chinese Medicine for respiratory infectious diseases. JOURNAL OF ETHNOPHARMACOLOGY 2023; 313:116381. [PMID: 36940735 DOI: 10.1016/j.jep.2023.116381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 02/24/2023] [Accepted: 03/08/2023] [Indexed: 05/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese medicine (TCM) has saved countless lives and maintained human health over its long history, especially in respiratory infectious diseases. The relationship between the intestinal flora and the respiratory system has been a popular research topic in recent years. According to the theory of the "gut-lung axis" in modern medicine and the idea that "the lung stands in an interior-exterior relationship with the large intestine" in TCM, gut microbiota dysbiosis is a contributing factor to respiratory infectious diseases, and there is potential means for manipulation of the gut microbiota in the treatment of lung diseases. Emerging studies have indicated intestinal Escherichia coli (E. coli) overgrowth in multiple respiratory infectious diseases, which could exacerbate respiratory infectious diseases by disrupting immune homeostasis, the gut barrier and metabolic balance. TCM is an effective microecological regulator, that can regulate the intestinal flora including E. coli, and restore the balance of the immune system, gut barrier, and metabolism. AIM OF THE REVIEW This review discusses the changes and effects of intestinal E. coli in respiratory infection, as well as the role of TCM in the intestinal flora, E. coli and related immunity, the gut barrier and the metabolism, thereby suggesting the possibility of TCM therapy regulating intestinal E. coli and related immunity, the gut barrier and the metabolism to alleviate respiratory infectious diseases. We aimed to make a modest contribution to the research and development of new therapies for intestinal flora in respiratory infectious diseases and the full utilization of TCM resources. Relevant information about the therapeutic potential of TCM to regulate intestinal E. coli against diseases was collected from PubMed, China National Knowledge Infrastructure (CNKI), and so on. The Plants of the World Online (https://wcsp.science.kew.org) and the Plant List (www.theplantlist.org) databases were used to provide the scientific names and species of plants. RESULTS Intestinal E. coli is a very important bacterium in respiratory infectious diseases that affects the respiratory system through immunity, the gut barrier and the metabolism. Many TCMs can inhibit the abundance of E. coli and regulate related immunity, the gut barrier and the metabolism to promote lung health. CONCLUSION TCM targeting intestinal E. coli and related immune, gut barrier, and metabolic dysfunction could be a potential therapy to promote the treatment and prognosis of respiratory infectious diseases.
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Affiliation(s)
- Lini Wei
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China
| | - Lulu Zhang
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China
| | - Yan Zhang
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China
| | - Lan Yan
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China
| | - Bin Liu
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China
| | - Zhiwen Cao
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China
| | - Ning Zhao
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China
| | - Xiaojuan He
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China.
| | - Li Li
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China.
| | - Cheng Lu
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, PR China.
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30
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Guo Y, Ma X, Nie Y, Kostallari E, Gao J. Editorial: Hepatic immune response underlying liver cirrhosis and portal hypertension. Front Immunol 2023; 14:1174562. [PMID: 36969230 PMCID: PMC10034766 DOI: 10.3389/fimmu.2023.1174562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Accepted: 02/27/2023] [Indexed: 03/11/2023] Open
Affiliation(s)
- Yangkun Guo
- Lab of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiong Ma
- Division of Gastroenterology and Hepatology, National Healthy Commission (NHC) Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, Shanghai, China
- *Correspondence: Enis Kostallari, ; Yongzhan Nie, ; Xiong Ma, ; Jinhang Gao,
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Military Medical University, Xi’an, China
- *Correspondence: Enis Kostallari, ; Yongzhan Nie, ; Xiong Ma, ; Jinhang Gao,
| | - Enis Kostallari
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
- *Correspondence: Enis Kostallari, ; Yongzhan Nie, ; Xiong Ma, ; Jinhang Gao,
| | - Jinhang Gao
- Lab of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Enis Kostallari, ; Yongzhan Nie, ; Xiong Ma, ; Jinhang Gao,
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The Role of Microbiota in Liver Transplantation and Liver Transplantation-Related Biliary Complications. Int J Mol Sci 2023; 24:ijms24054841. [PMID: 36902269 PMCID: PMC10003075 DOI: 10.3390/ijms24054841] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/22/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Liver transplantation as a treatment option for end-stage liver diseases is associated with a relevant risk for complications. On the one hand, immunological factors and associated chronic graft rejection are major causes of morbidity and carry an increased risk of mortality due to liver graft failure. On the other hand, infectious complications have a major impact on patient outcomes. In addition, abdominal or pulmonary infections, and biliary complications, including cholangitis, are common complications in patients after liver transplantation and can also be associated with a risk for mortality. Thereby, these patients already suffer from gut dysbiosis at the time of liver transplantation due to their severe underlying disease, causing end-stage liver failure. Despite an impaired gut-liver axis, repeated antibiotic therapies can cause major changes in the gut microbiome. Due to repeated biliary interventions, the biliary tract is often colonized by several bacteria with a high risk for multi-drug resistant germs causing local and systemic infections before and after liver transplantation. Growing evidence about the role of gut microbiota in the perioperative course and their impact on patient outcomes in liver transplantation is available. However, data about biliary microbiota and their impact on infectious and biliary complications are still sparse. In this comprehensive review, we compile the current evidence for the role of microbiome research in liver transplantation with a focus on biliary complications and infections due to multi-drug resistant germs.
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Song JJ, Wu CJ, Dong YY, Ma C, Gu Q. Unexplained septic shock after colonoscopy with polyethylene glycol preparation in a young adult: A case report. World J Clin Cases 2022; 10:11652-11657. [PMID: 36387829 PMCID: PMC9649567 DOI: 10.12998/wjcc.v10.i31.11652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/15/2022] [Accepted: 09/27/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Colonoscopy has become a routine physical examination as people’s health awareness has increased. Polyethylene glycol (PEG) is greatly used in bowel preparation before colonoscopy due to its price and safety advantages. Septic shock after colonoscopy with PEG preparation is extremely rare, with only very few cases in critically ill patients. Herein, we describe a case of septic shock in a healthy young adult immediately following colonoscopy with PEG preparation.
CASE SUMMARY A 33-year-old young adult presented to our hospital for colonoscopy with PEG bowel preparation due to recurrent diarrhea for 7 years. The male's previous physical examination showed no abnormal indicators, and colonoscopy results were normal; however, he exhibited septic shock and markedly elevated white blood cell, C-reactive protein, and procalcitonin levels on the second day after colonoscopy. Immediate resuscitation and intensive care with appropriate antibiotics improved his condition. However, the blood and stool cultures did not detect the pathogen
CONCLUSION Septic shock after colonoscopy is rare, especially in young adults. The authors considered the possibility of opportunistic infections after PEG bowel preparation, and clinicians should monitor patients for the possibility of such complications
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Affiliation(s)
- Jiao-Jiao Song
- Department of Gastrointestinal Endoscopy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Chen-Jiao Wu
- Department of Gastrointestinal Endoscopy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Yuan-Yuan Dong
- Department of Gastrointestinal Endoscopy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Can Ma
- Department of Gastrointestinal Endoscopy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Qing Gu
- Department of Gastrointestinal Endoscopy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
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Zhao Y, Zhou R, Guo Y, Chen X, Zhang A, Wang J, Ji F, Qin B, Geng J, Kong G, Li Z. Improvement of gut microbiome and intestinal permeability following splenectomy plus pericardial devascularization in hepatitis B virus-related cirrhotic portal hypertension. Front Immunol 2022; 13:941830. [PMID: 36159870 PMCID: PMC9493484 DOI: 10.3389/fimmu.2022.941830] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 08/15/2022] [Indexed: 11/17/2022] Open
Abstract
The gut microbiome is an essential component of the intestinal mucosal barrier, critical in regulating intestinal permeability. Microbiome dysbiosis and intestinal permeability changes are commonly encountered conditions in patients with cirrhosis and are closely related to its development and further complications. However, alterations in the gut microbiome and intestinal permeability in chronic hepatitis B virus (HBV) patients with cirrhotic portal hypertension after undergoing a splenectomy plus pericardial devascularization (SPD) have not been investigated. This study recruited 22 patients who were measured against themselves on the study parameters before and after an SPD, along with 20 healthy controls. Methodologically, fecal samples were collected for gut microbiome analysis by 16S ribosomal DNA sequencing, and peripheral blood samples were obtained to examine the liver function and intestinal permeability. This study showed that the community structure of the gut microbiomes in patients before the SPD exhibited obvious differences from those in the healthy control group. They also exhibited a decreased bacterial community richness, increased intestinal permeability, and enhanced inflammation compared with the healthy controls. These issues were further aggravated two weeks after the SPD. There was also evidence of significantly higher abundances of Streptococcaceae, Enterobacteriaceae, and Enterococcaceae than those in the healthy control group. However, 12 months after the surgery, 12 of the 16 patient-associated genera recovered, of which 10 reached normal levels. Additionally, the microbiome diversity increased; the bacterial composition was back to a level similar to the healthy controls. Liver function, intestinal permeability, and inflammation levels all improved compared with preoperative levels. Furthermore, correlation analyses indicated that the five recovered bacterial taxa and the Shannon diversity index were correlated with several improved clinical indicators. Altogether, the improvements in the liver function and intestinal permeability in HBV-related cirrhotic patients may be related to the restoration of the gut microbiome after an SPD.
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Affiliation(s)
- Yang Zhao
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Rui Zhou
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Ying Guo
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xi Chen
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Aiyu Zhang
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jiayin Wang
- School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, China
| | - Fanpu Ji
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Bowen Qin
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jing Geng
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Guangyao Kong
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zongfang Li
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Maslennikov R, Efremova I, Ivashkin V, Zharkova M, Poluektova E, Shirokova E, Ivashkin K. Effect of probiotics on hemodynamic changes and complications associated with cirrhosis: A pilot randomized controlled trial. World J Hepatol 2022; 14:1667-1677. [PMID: 36157871 PMCID: PMC9453455 DOI: 10.4254/wjh.v14.i8.1667] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/12/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease course. Probiotics may reduce bacterial translocation and may therefore be useful to redress the circulatory imbalance. AIM To investigate the effect of probiotics on hemodynamic parameters, systemic inflammation, and complications of cirrhosis in this randomized placebo-controlled trial. METHODS This single-blind randomized placebo-controlled study included 40 patients with Child-Pugh class B and C cirrhosis; 24 patients received probiotics (Saccharomyces boulardii) for 3 mo, and 16 patients received a placebo over the same period. Liver function and the systemic hemodynamic status were evaluated pre- and post-intervention. Echocardiography and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic indicators. Cardiac output and systemic vascular resistance were calculated. RESULTS Following a 3-mo course of probiotics in comparison to the control group, we observed amelioration of hyperdynamic circulation [a decrease in cardiac output (P = 0.026) and an increase in systemic vascular resistance (P = 0.026)] and systemic inflammation [a decrease in serum C-reactive protein levels (P = 0.044)], with improved liver function [an increase in serum albumin (P = 0.001) and a decrease in the value of Child-Pugh score (P = 0.001)] as well as a reduction in the severity of ascites (P = 0.022), hepatic encephalopathy (P = 0.048), and cholestasis [a decrease in serum alkaline phosphatase (P = 0.016) and serum gamma-glutamyl transpeptidase (P = 0.039) activity] and an increase in platelet counts (P < 0.001) and serum sodium level (P = 0.048). CONCLUSION Probiotic administration was associated with amelioration of hyperdynamic circulation and the associated complications of cirrhosis.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
- Consultative and Diagnostic Center No. 2 of Moscow Health Department , Moscow 107764, Russia.
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Maria Zharkova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Elena Shirokova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Konstantin Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
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Santopaolo F, Coppola G, Giuli L, Gasbarrini A, Ponziani FR. Influence of Gut–Liver Axis on Portal Hypertension in Advanced Chronic Liver Disease: The Gut Microbiome as a New Protagonist in Therapeutic Management. MICROBIOLOGY RESEARCH 2022; 13:539-555. [DOI: 10.3390/microbiolres13030038] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Clinically significant portal hypertension is associated with most complications of advanced chronic liver disease (ACLD), including variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. Gut dysbiosis is a hallmark of ACLD with portal hypertension and consists of the overgrowth of potentially pathogenic bacteria and a decrease in autochthonous bacteria; additionally, congestion makes the intestinal barrier more permeable to bacteria and their products, which contributes to the development of complications through inflammatory mechanisms. This review summarizes current knowledge on the role of the gut–liver axis in the pathogenesis of portal hypertension, with a focus on therapies targeting portal hypertension and the gut microbiota. The modulation of the gut microbiota on several levels represents a major challenge in the upcoming years; in-depth characterization of the molecular and microbiological mechanisms linking the gut–liver axis to portal hypertension in a bidirectional relationship could pave the way to the identification of new therapeutic targets for innovative therapies in the management of ACLD.
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Affiliation(s)
- Francesco Santopaolo
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Gaetano Coppola
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Lucia Giuli
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Wang Q, Huang J, Liu S, Wang C, Jin Y, Lai H, Tu W. Aberrant hepatic lipid metabolism associated with gut microbiota dysbiosis triggers hepatotoxicity of novel PFOS alternatives in adult zebrafish. ENVIRONMENT INTERNATIONAL 2022; 166:107351. [PMID: 35738203 DOI: 10.1016/j.envint.2022.107351] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 06/11/2022] [Accepted: 06/13/2022] [Indexed: 05/23/2023]
Abstract
Perfluorooctane sulfonate (PFOS) has been reported to induce hepatotoxicity in wildlife and humans. Novel PFOS alternatives have been widely used following restrictions on PFOS, but little is known about their potential toxicity. Here, the first comprehensive investigation on the chronic hepatotoxicity and underlying molecular mechanisms of PFOS, 6:2Cl-PFESA (F-53B), and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) was carried out on adult zebrafish through a histopathological examination, biochemical measurement, and multi-omics analysis. PFOS and its alternatives caused changes in liver histopathology and liver function indices in the order of F-53B > PFOS > OBS, which was consistent with their concentration in the liver. In silico modeling and transcriptional profiles suggested that the aberrant hepatic lipid metabolism induced by F-53B and PFOS was initiated by the action on peroxisome proliferator-activated receptor γ (PPARγ), which triggered changes in downstream genes transcription and led to an imbalance between lipid synthesis and expenditure. Gut microbiome analysis provided another novel mechanistic perspective that changes in the abundance of Legionella, Ralstonia, Brevundimonas, Alphaproteobacteria, Plesiomonas, and Hyphomicrobium might link to alterations in the PPAR pathway based on their significant correlation. This study provides insight into the molecular mechanisms of hepatotoxicity induced by PFOS and its novel alternatives and highlights the need for concern about their environmental exposure risks.
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Affiliation(s)
- Qiyu Wang
- Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330012, China
| | - Jing Huang
- Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330012, China; School of Land Resources and Environment, Jiangxi Agricultural University, Nanchang 330045, China
| | - Shuai Liu
- Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330012, China
| | - Caiyun Wang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Yuanxiang Jin
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
| | - Hong Lai
- Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330012, China
| | - Wenqing Tu
- School of Land Resources and Environment, Jiangxi Agricultural University, Nanchang 330045, China.
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Kulkarni AV, Premkumar M, Arab JP, Kumar K, Sharma M, Reddy ND, Padaki NR, Reddy RK. Early Diagnosis and Prevention of Infections in Cirrhosis. Semin Liver Dis 2022; 42:293-312. [PMID: 35672014 DOI: 10.1055/a-1869-7607] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Strategies to prevent infection and improve outcomes in patients with cirrhosis. HAV, hepatitis A virus; HBV, hepatitis B virus; COVID-19, novel coronavirus disease 2019; NSBB, nonselective β-blocker; PPI, proton pump inhibitors.Cirrhosis is a risk factor for infections. Majority of hospital admissions in patients with cirrhosis are due to infections. Sepsis is an immunological response to an infectious process that leads to end-organ dysfunction and death. Preventing infections may avoid the downstream complications, and early diagnosis of infections may improve the outcomes. In this review, we discuss the pathogenesis, diagnosis, and biomarkers of infection; the incremental preventive strategies for infections and sepsi; and the consequent organ failures in cirrhosis. Strategies for primary prevention include reducing gut translocation by selective intestinal decontamination, avoiding unnecessary proton pump inhibitors' use, appropriate use of β-blockers, and vaccinations for viral diseases including novel coronavirus disease 2019. Secondary prevention includes early diagnosis and a timely and judicious use of antibiotics to prevent organ dysfunction. Organ failure support constitutes tertiary intervention in cirrhosis. In conclusion, infections in cirrhosis are potentially preventable with appropriate care strategies to then enable improved outcomes.
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Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Juan P Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Karan Kumar
- Department of Hepatology, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India
| | - Mithun Sharma
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Nageshwar D Reddy
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Nagaraja R Padaki
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
| | - Rajender K Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
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Gao TH, Liao W, Lin LT, Zhu ZP, Lu MG, Fu CM, Xie T. Curcumae rhizoma and its major constituents against hepatobiliary disease: Pharmacotherapeutic properties and potential clinical applications. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 102:154090. [PMID: 35580439 DOI: 10.1016/j.phymed.2022.154090] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 02/25/2022] [Accepted: 03/28/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Hepatobiliary disease currently serves as an urgent health issue in public due to health-modulating factors such as extension of life expectancy, increasingly sedentary lifestyles and over-nutrition. A definite treatment remains lacking owing to different stages of the disease itself and its intricate pathogenesis. Traditional Chinese medicine (TCM) has been gradually popularized in clinic with the satisfactory efficacy and good safety. Curcumae Rhizoma (called E Zhu, EZ in Chinese) is a representative herb, which has been used to treat hepatobiliary disease for thousands of years. PURPOSE To systematically summarize the recent research advances on the pharmacological activities of EZ and its constituents, explain the underlying mechanisms of preventing and treating hepatobiliary diseases, and assess the shortcomings of existing work. Besides, ethnopharmacology, phytochemicals, and toxicology of EZ have been researched. METHODS The information about EZ was collected from various sources including classic books about Chinese herbal medicine, and scientific databases including Web of Science, PubMed, ScienceDirect, Springer, ACS, SCOPUS, CNKI, CSTJ, and WANFANG using keywords given below and terms like pharmacological and phytochemical details of this plant. RESULTS The chemical constituents isolated and identified from EZ, such as terpenoids including β-elemene, furanodiene, germacrone, etc. and curcuminoids including curcumin, demethoxycurcumin, bisdemethoxycurcumin, etc. prove to have hepatoprotective effect, anti-liver fibrotic effect, anti-fatty liver effect, anti-liver neoplastic effect, and cholagogic effect through TGF-β1/Smad, JNK1/2-ROS, NF-κB and other anti-inflammatory and antioxidant signaling pathways. Also, EZ is often combined with other Chinese herbs in the treatment of hepatobiliary diseases with good clinical efficacy and no obvious adverse reactions. CONCLUSION It provides a preclinical basis for the efficacy of EZ as an effective therapeutic agent for the prevention and treatment of hepatobiliary diseases. Even so, the further studies still needed to alleviate hepatotoxicity and expand clinical application.
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Affiliation(s)
- Tian-Hui Gao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Wan Liao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Li-Ting Lin
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Zong-Ping Zhu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Mei-Gui Lu
- Huachiew TCM Hospital, Bangkok 10100, Thailand
| | - Chao-Mei Fu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Tian Xie
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
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Cicuttin GL, De Salvo MN, Hercolini C, Arístegui E, Bruno A, Brambati D, Nava S. Detection of Neorickettsia sp. in Oligoryzomys flavescens rodent from a protected urban area in Buenos Aires City (Argentina). Vet Parasitol Reg Stud Reports 2022; 32:100742. [PMID: 35725109 DOI: 10.1016/j.vprsr.2022.100742] [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: 09/21/2021] [Revised: 03/28/2022] [Accepted: 05/19/2022] [Indexed: 06/15/2023]
Abstract
Rodents play an important role in vector-borne pathogens cycle. To detect Anaplasma, Ehrlichia, Neorickettsia, Rickettsia and Borrelia species in rodents from a protected urban area in Buenos Aires City (Argentina) were analyzed 203 organ pools of Mus musculus, Oligoryzomys flavescens, Rattus norvegicus, Deltamys kempi and Scapteromys aquaticus by PCR. Only one O. flavescens (1.2%) was positive by PCR for 16S rRNA fragment for the Anaplasmataceae family and the sequence had 99.7% identity with Neorickettsia risticii. Plus, the sequence obtained for a fragment of the p51 gene for the genus Neorickettsia from positive sample had 95.3-96.1% identity with N. risticii found previously in bats Tadarida brasiliensis from Buenos Aires City. Our study presents the first finding of Neorickettsia in rodents from natural environment, but further studies are necessary about these vector-borne bacteria and the rol of rodents in its epidemiology.
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Affiliation(s)
- G L Cicuttin
- Instituto de Zoonosis Luis Pasteur, Av. Díaz Vélez 4821, CP 1405 Ciudad Autónoma de Buenos Aires, Argentina.
| | - M N De Salvo
- Instituto de Zoonosis Luis Pasteur, Av. Díaz Vélez 4821, CP 1405 Ciudad Autónoma de Buenos Aires, Argentina
| | - C Hercolini
- Instituto de Zoonosis Luis Pasteur, Av. Díaz Vélez 4821, CP 1405 Ciudad Autónoma de Buenos Aires, Argentina
| | - E Arístegui
- Instituto de Zoonosis Luis Pasteur, Av. Díaz Vélez 4821, CP 1405 Ciudad Autónoma de Buenos Aires, Argentina
| | - A Bruno
- Instituto de Zoonosis Luis Pasteur, Av. Díaz Vélez 4821, CP 1405 Ciudad Autónoma de Buenos Aires, Argentina; Independent
| | - D Brambati
- Instituto de Zoonosis Luis Pasteur, Av. Díaz Vélez 4821, CP 1405 Ciudad Autónoma de Buenos Aires, Argentina
| | - S Nava
- Instituto de Investigación de la Cadena Láctea (INTA-CONICET), Instituto Nacional de Tecnología Agropecuaria, Estación Experimental Agropecuaria Rafaela, Ruta 34 Km 227, CP 2300 Rafaela, Santa Fe, Argentina
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Wong HJ, Lim WH, Ng CH, Tan DJH, Bonney GK, Kow AWC, Huang DQ, Siddiqui MS, Noureddin M, Syn N, Muthiah MD. Predictive and Prognostic Roles of Gut Microbial Variation in Liver Transplant. Front Med (Lausanne) 2022; 9:873523. [PMID: 35620719 PMCID: PMC9127379 DOI: 10.3389/fmed.2022.873523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/06/2022] [Indexed: 11/16/2022] Open
Abstract
Patients undergoing liver transplant (LTX) typically confront a challenging postoperative journey. A dysbiotic gut microbiome is associated with the development of complications, including post-LTX allograft rejection, metabolic diseases and de novo or recurrent cancer. A major explanation of this are the bipartite interactions between the gut microbiota and host immunity, which modulates the alloimmune response towards the liver allograft. Furthermore, bacterial translocation from dysbiosis causes pathogenic changes in the concentrations of microbial metabolites like lipopolysaccharides, short-chain fatty acids (SCFAs) and Trimethylamine-N-Oxide, with links to cardiovascular disease development and diabetes mellitus. Gut dysbiosis also disrupts bile acid metabolism, with implications for various post-LTX metabolic diseases. Certain taxonomy of microbiota such as lactobacilli, F.prausnitzii and Bacteroides appear to be associated with these undesired outcomes. As such, an interesting but as yet unproven hypothesis exists as to whether induction of a “beneficial” composition of gut microbiota may improve prognosis in LTX patients. Additionally, there are roles of the microbiome as predictive and prognostic indicators for clinicians in improving patient care. Hence, the gut microbiome represents an exceptionally exciting avenue for developing novel prognostic, predictive and therapeutic applications.
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Affiliation(s)
- Hon Jen Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Glenn K Bonney
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University Hospital Singapore, Singapore, Singapore
| | - Alfred W C Kow
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.,Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University Hospital Singapore, Singapore, Singapore
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, United States
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Centre, Cedars-Sinai Medical Centre, Los Angeles, CA, United States
| | - Nicholas Syn
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mark D Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
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Kholodnaia A, So-Armah K, Cheng D, Gnatienko N, Patts G, Samet JH, Freiberg M, Lioznov D. Impact of illicit opioid use on markers of monocyte activation and systemic inflammation in people living with HIV. PLoS One 2022; 17:e0265504. [PMID: 35511802 PMCID: PMC9070930 DOI: 10.1371/journal.pone.0265504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 03/02/2022] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION We hypothesize that illicit opioid use increases bacterial translocation from the gut, which intensifies systemic inflammation. OBJECTIVE To investigate the association between opioid use and plasma soluble CD14 [sCD14], interleukin-6 [IL-6] and D-dimer in people living with HIV (PLWH). METHODS We analyzed data from the Russia ARCH study-an observational cohort of 351 ART-naive PLWH in St. Petersburg, Russia. Plasma levels of sCD14 (primary outcome), IL-6 and D-dimer (secondary outcomes) were evaluated at baseline, 12, and 24 months. Participants were categorized into three groups based on illicit opioid use: current, prior, and never opioid use. Linear mixed effects models were used to evaluate associations. RESULTS Compared to never opioid use, sCD14 levels were significantly higher for participants with current opioid use (AMD = 197.8 ng/ml [11.4, 384.2], p = 0.04). IL-6 levels were also higher for participants with current vs. never opioid use (ARM = 2.10 [1.56, 2.83], p <0.001). D-dimer levels were higher for current (ARM = 1.95 [1.43, 2.64], p <0.001) and prior (ARM = 1.57 [1.17, 2.09], p = 0.004) compared to never opioid use. CONCLUSIONS Among PLWH, current opioid use compared to never use is associated with increased monocyte activation and systemic inflammation.
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Affiliation(s)
- Anastasia Kholodnaia
- Department of Infectious Diseases and Epidemiology, Academician I.P. Pavlov First St. Petersburg State Medical University, Saint-Petersburg, Russian Federation
| | - Kaku So-Armah
- Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine/Boston Medical Center, Clinical Addiction Research and Education (CARE) Unit, Boston, MA, United States of America
| | - Debbie Cheng
- Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America
| | - Natalia Gnatienko
- Department of Medicine, Section of General Internal Medicine, Boston Medical Center, Clinical Addiction Research and Education (CARE) Unit, Boston, MA, United States of America
| | - Gregory Patts
- Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston University School of Public Health, Boston, MA, United States of America
| | - Jeffrey H. Samet
- Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine/Boston Medical Center, Clinical Addiction Research and Education (CARE) Unit, Boston, MA, United States of America
- Department of Community Health Sciences, Boston University School of Public Health, Boston, MA, United States of America
| | - Matthew Freiberg
- Vanderbilt Center for Clinical Cardiovascular Trials Evaluation (V-C3REATE), Vanderbilt University Medical Center, Cardiovascular Division, Nashville, TN, United States of America
| | - Dmitry Lioznov
- Department of Infectious Diseases and Epidemiology, Academician I.P. Pavlov First St. Petersburg State Medical University, Saint-Petersburg, Russian Federation
- Smorodintsev Research Institute of Influenza, St. Petersburg, Russian Federation
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Zhao Z, Wang J, Ren W, Bian Y, Wang Y, Wang L, Guo L, Lei J, Jia J, Miao J. Effect of Jiangan-Jiangzhi Pill on Gut Microbiota and Chronic Inflammatory Response in Rats with Non-Alcoholic Fatty Liver. Chem Biodivers 2022; 19:e202100987. [PMID: 35324083 DOI: 10.1002/cbdv.202100987] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 03/22/2022] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with high rates of occurrence. Research has found that NAFLD patients experience varying degrees of intestinal flora imbalance. There is evidence that traditional Chinese medicine (TCM) positively regulates imbalances in the gut microbiota caused by liver diseases. Jiangan-Jiangzhi pill (JGJZ) is a common Chinese remedy that can treat NAFLD clinically. This article investigates how JGJZ affects NAFLD and assesses related changes in the intestinal flora. We established a NAFLD rat model by feeding them a high-fat diet (HFD) and gave different interventions. After twelve weeks, the results revealed that JGJZ decreased the total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase in the serum of NAFLD rats. Histopathological staining demonstrated that JGJZ relieved cellular fat accumulation in the liver. Inflammatory cytokine levels (IL-6, IL-1β, and TNF-α) were down-regulated. Analysis of 16S rRNA demonstrated that JGJZ changed the community compositional structure of gut microbiota, characterized by a decrease in the Firmicutes-to-Bacteroidetes ratio, and increased gut microbiota diversity and the abundance of dominant groups. Accordingly, our study illustrated that JGJZ exerted a better effect in treating HFD-induced NAFLD, which may be closely related to ameliorating gut microbiota dysbiosis.
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Affiliation(s)
- Zeyu Zhao
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, No. 10, Poyanghu Road, Town West Area, Jinghai District, Tianjin, 301617, China
| | - Jing Wang
- Department of Integrated Traditional Chinese and Western Medicine, Tianjin Second People's Hospital, No.7, Sudi Nan Road, Nankai District, Tianjin, 300192, China
| | - Wei Ren
- Department of Integrated Traditional Chinese and Western Medicine, Tianjin Second People's Hospital, No.7, Sudi Nan Road, Nankai District, Tianjin, 300192, China
| | - Yuhong Bian
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, No. 10, Poyanghu Road, Town West Area, Jinghai District, Tianjin, 301617, China
| | - Yixi Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, No. 10, Poyanghu Road, Town West Area, Jinghai District, Tianjin, 301617, China
| | - Li Wang
- Department of Pharmacy, Tianjin Second People's Hospital, No. 7, Sudi Nan Road, Naikai District, Tianjin, 300192, China
| | - Liying Guo
- Department of Integrated Traditional Chinese and Western Medicine, Tianjin Second People's Hospital, No.7, Sudi Nan Road, Nankai District, Tianjin, 300192, China
| | - Jinyan Lei
- Department of Integrated Traditional Chinese and Western Medicine, Tianjin Second People's Hospital, No.7, Sudi Nan Road, Nankai District, Tianjin, 300192, China
| | - Jianwei Jia
- Department of Integrated Traditional Chinese and Western Medicine, Tianjin Second People's Hospital, No.7, Sudi Nan Road, Nankai District, Tianjin, 300192, China
| | - Jing Miao
- Department of Integrated Traditional Chinese and Western Medicine, Tianjin Second People's Hospital, No.7, Sudi Nan Road, Nankai District, Tianjin, 300192, China
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Maslennikov R, Ivashkin V, Efremova I, Poluektova E, Kudryavtseva A, Krasnov G. Gut dysbiosis and small intestinal bacterial overgrowth as independent forms of gut microbiota disorders in cirrhosis. World J Gastroenterol 2022; 28:1067-1077. [PMID: 35431497 PMCID: PMC8968519 DOI: 10.3748/wjg.v28.i10.1067] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/29/2021] [Accepted: 02/09/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gut dysbiosis and small intestinal bacterial overgrowth (SIBO) are commonly observed in patients with cirrhosis. Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis, dysbiosis and SIBO were always studied separately. AIM To study the relationship of gut dysbiosis and SIBO in cirrhosis. METHODS This observational study included 47 in-patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. SIBO was assessed using the lactulose hydrogen breath test. RESULTS SIBO was found in 24/47 (51.1%) patients. Patients with SIBO had a higher abundance of Firmicutes (P = 0.017) and Fusobacteria (P = 0.011), and a lower abundance of Bacteroidetes (P = 0.013) than patients without SIBO. This increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia (P = 0.020) of the Lachnospiraceae family (P = 0.047), while the abundance of other major families of this phylum [Ruminococcaceae (P = 0.856), Peptostreptococcaceae (P = 0.066), Clostridiaceae (P = 0.463), Eubacteriaceae (P = 0.463), Lactobacillaceae (P = 0.413), and Veillonellaceae (P = 0.632)] did not differ significantly between the patients with and without SIBO. Reduced level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum [Bacteroidaceae (P = 0.014), Porphyromonadaceae (P = 0.002), and Rikenellaceae (P = 0.047)], with the exception of Prevotellaceae (P = 0.941). There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis [Proteobacteria (P = 0.790), Bacilli (P = 0.573), Enterobacteriaceae (P = 0.632), Streptococcaceae (P = 0.170), Staphylococcaceae (P = 0.450), and Enterococcaceae (P = 0.873)] between patients with and without SIBO. CONCLUSION Despite the differences observed in the gut microbiome between patients with and without SIBO, gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
- Department of Internal Medicine 1, Сonsultative and Diagnostic Center 2 of the Moscow City Health Department, Moscow 107564, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Anna Kudryavtseva
- Scientific Community for Human Microbiome Research, Moscow 119435, Russia
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
| | - George Krasnov
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
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Wells J, Bai J, Tsementzi D, Jhaney CI, Foster A, Watkins Bruner D, Gillespie T, Li Y, Hu YJ. Exploring the Anal Microbiome in HIV Positive and High-Risk HIV Negative Women. AIDS Res Hum Retroviruses 2022; 38:228-236. [PMID: 35044233 PMCID: PMC8968844 DOI: 10.1089/aid.2020.0245] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
This exploratory study sought to characterize the anal microbiome and explore associations among the anal microbiome, risk factors for anal cancer, and clinical factors. A pilot sample of 50 HIV infected and high-risk HIV negative women were recruited from the former Women's Interagency HIV Study. Microbiome characterization by 16S rRNA gene sequencing and datasets were analyzed using QIIME 2™. Composition of the anal microbiome and its associations with anal cancer risk factors and clinical factors were analyzed using linear decomposition model and permutational multivariate analysis of variance. Composition of the anal microbiome among HIV positive and high-risk negative women was dominated by Bacteroides, Prevotella, and Campylobacter. The overall taxonomic composition and microbial diversity of the anal microbiome did not significantly differ by HIV status. However, the abundance of Ruminococcus 1 belonging to the Rumincoccaceae family was associated with HIV status (q = .05). No anal cancer risk factors were associated with the anal microbiome composition. Clinical factors marginally associated with the anal microbiome composition included body mass index (BMI; p = .05) and hepatitis C virus (HCV; p = .05). Although HIV and risk factors for anal cancer were not associated with the composition of the anal microbiome in this pilot sample, other clinical factors such as BMI and HCV, may be worth further investigation in a larger study. Future research can build on these findings to explore the role of the microbiome and HIV comorbidities in women.
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Affiliation(s)
- Jessica Wells
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA.,Address correspondence to: Jessica Wells, Nell Hodgson Woodruff School of Nursing, Emory University, 1520 Clifton Road NE, Room 230, Atlanta, GA 30322-1007, USA
| | - Jinbing Bai
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA
| | - Despina Tsementzi
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA
| | - Camber Ileen Jhaney
- Department of Surgery and Department of Hematology & Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Antonina Foster
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Deborah Watkins Bruner
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA.,Department of Surgery and Department of Hematology & Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Theresa Gillespie
- Department of Surgery and Department of Hematology & Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Yunxiao Li
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Yi-Juan Hu
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
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45
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Gedgaudas R, Bajaj JS, Skieceviciene J, Varkalaite G, Jurkeviciute G, Gelman S, Valantiene I, Zykus R, Pranculis A, Bang C, Franke A, Schramm C, Kupcinskas J. Circulating microbiome in patients with portal hypertension. Gut Microbes 2022; 14:2029674. [PMID: 35130114 PMCID: PMC8824227 DOI: 10.1080/19490976.2022.2029674] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Portal hypertension (PH) in liver cirrhosis leads to increased gut permeability and the translocation of bacteria across the gut-liver axis. Microbial DNA has recently been detected in different blood compartments; however, this phenomenon has not been thoroughly analyzed in PH. This study aimed to explore circulating bacterial DNA signatures, inflammatory cytokines, and gut permeability markers in different blood compartments (peripheral and hepatic veins) of patients with cirrhosis and PH. The 16S rRNA blood microbiome profiles were determined in 58 patients with liver cirrhosis and 46 control patients. Taxonomic differences were analyzed in relation to PH, liver function, inflammatory cytokines, and gut permeability markers. Circulating plasma microbiome profiles in patients with cirrhosis were distinct from those of the controls and were characterized by enrichment of Comamonas, Cnuella, Dialister, Escherichia/Shigella, and Prevotella and the depletion of Bradyrhizobium, Curvibacter, Diaphorobacter, Pseudarcicella, and Pseudomonas. Comparison of peripheral and hepatic vein blood compartments of patients with cirrhosis did not reveal differentially abundant taxa. Enrichment of the genera Bacteroides, Escherichia/Shigella, and Prevotella was associated with severe PH (SPH) in both blood compartments; however, circulating microbiome profiles could not predict PH severity. Escherichia/Shigella and Prevotella abundance was correlated with IL-8 levels in the hepatic vein. In conclusion, we demonstrated a distinct circulating blood microbiome profile in patients with cirrhosis, showing that specific bacterial genera in blood are marginally associated with SPH, Model for End-Stage Liver Disease score, and inflammation biomarkers; however, circulating microbial composition failed to predict PH severity.
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Affiliation(s)
- Rolandas Gedgaudas
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania,Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Jasmohan S Bajaj
- Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
| | - Jurgita Skieceviciene
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Greta Varkalaite
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Gabija Jurkeviciute
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Sigita Gelman
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania,Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Irena Valantiene
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania,Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Romanas Zykus
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania,Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Andrius Pranculis
- Department of Radiology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Corinna Bang
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Christoph Schramm
- Ist Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany,Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Juozas Kupcinskas
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania,Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania,CONTACT Juozas Kupcinskas Lithuanian University of Health Sciences, Medical Academy, Department of Gastroenterology & Institute for Digestive Research, Mickeviciaus 9a, Kaunas, Lithuania, LT-44307
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46
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Voland L, Le Roy T, Debédat J, Clément K. Gut microbiota and vitamin status in persons with obesity: A key interplay. Obes Rev 2022; 23:e13377. [PMID: 34767276 DOI: 10.1111/obr.13377] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/04/2021] [Accepted: 10/05/2021] [Indexed: 12/28/2022]
Abstract
There are numerous factors involved in obesity progression and maintenance including systemic low-grade inflammation, adipose tissue dysfunction, or gut microbiota dysbiosis. Recently, a growing interest has arisen for vitamins' role in obesity and related disorders, both at the host and gut bacterial level. Indeed, vitamins are provided mostly by food, but some, from the B and K groups in particular, can be synthesized by the gut bacterial ecosystem and absorbed in the colon. Knowing that vitamin deficiency can alter many important cellular functions and lead to serious health issues, it is important to carefully monitor the vitamin status of patients with obesity and potentially already existing comorbidities as well as to examine the dysbiotic gut microbiota and thus potentially altered bacterial metabolism of vitamins. In this review, we examined both murine and human studies, to assess the prevalence of sub-optimal levels of several vitamins in obesity and metabolic alterations. This review also examines the relationship between vitamins and the gut microbiota in terms of vitamin production and the modulation of the gut bacterial ecosystem in conditions of vitamin shortage or supplementation. Furthermore, some strategies to improve vitamin status of patients with severe obesity are proposed within this review.
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Affiliation(s)
- Lise Voland
- Inserm, Sorbonne University, Nutrition and obesities: systemic approaches (NutriOmics), Paris, France
| | - Tiphaine Le Roy
- Inserm, Sorbonne University, Nutrition and obesities: systemic approaches (NutriOmics), Paris, France
| | - Jean Debédat
- Inserm, Sorbonne University, Nutrition and obesities: systemic approaches (NutriOmics), Paris, France
| | - Karine Clément
- Inserm, Sorbonne University, Nutrition and obesities: systemic approaches (NutriOmics), Paris, France.,Public hospital of Paris, Nutrition department, Pitié-Salpêtrière Hospital, Paris, France
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47
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Aslam A, Barlas U, Yassan LJ, Lodhi M. An unusual case of gastric outlet obstruction and melena. Clin J Gastroenterol 2022; 15:374-380. [DOI: 10.1007/s12328-021-01584-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 12/24/2021] [Indexed: 11/28/2022]
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48
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Scheithauer TPM, Bakker GJ, Winkelmeijer M, Davids M, Nieuwdorp M, van Raalte DH, Herrema H. Compensatory intestinal immunoglobulin response after vancomycin treatment in humans. Gut Microbes 2022; 13:1-14. [PMID: 33475461 PMCID: PMC7833805 DOI: 10.1080/19490976.2021.1875109] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Intestinal immunoglobulins (Ig) are abundantly secreted antibodies that bind bacteria and bacterial components in the gut. This binding is considered to accelerate bacterial transit time and prevent the interaction of potentially immunogenic compounds with intestinal immune cells. Ig secretion is regulated by alterations in gut microbiome composition, an event rarely mapped in an intervention setting in humans. Here, we determined the intestinal and systemic Ig response to a major intervention in gut microbiome composition. Healthy humans and humans with metabolic syndrome received oral vancomycin 500 mg four times per day for 7 days. Coinciding with a vancomycin-induced increase in Gram-negative bacteria, fecal levels of the immunogenic bacterial components lipopolysaccharide (LPS) and flagellin drastically increased. Intestinal antibodies (IgA and IgM) significantly increased, whereas peripheral antibodies (IgG, IgA, and IgM) were mostly unaffected by vancomycin treatment. Bacterial cell sorting followed by 16S rRNA sequencing revealed that the majority of Gram-negative bacteria, including opportunistic pathogens, were IgA-coated after the intervention. We suggest that the intestinal Ig response after vancomycin treatment prevents the intrusion of pathogens and bacterial components into systemic sites.
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Affiliation(s)
- Torsten P. M. Scheithauer
- Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC at University of Amsterdam, Amsterdam, The Netherlands,Department of Internal Medicine, Diabetes Center, Amsterdam UMC, Location VUmc at Vrije Universiteit Amsterdam, Amsterdam, The Netherlands,CONTACT Torsten P. M. Scheithauer Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC, Meibergdreef 9, Room G1-115, Amsterdam1105 AZ, The Netherlands
| | - Guido J. Bakker
- Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC at University of Amsterdam, Amsterdam, The Netherlands
| | - Maaike Winkelmeijer
- Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC at University of Amsterdam, Amsterdam, The Netherlands
| | - Mark Davids
- Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC at University of Amsterdam, Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC at University of Amsterdam, Amsterdam, The Netherlands,Department of Internal Medicine, Diabetes Center, Amsterdam UMC, Location VUmc at Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Daniël H. van Raalte
- Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC at University of Amsterdam, Amsterdam, The Netherlands,Department of Internal Medicine, Diabetes Center, Amsterdam UMC, Location VUmc at Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Hilde Herrema
- Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC at University of Amsterdam, Amsterdam, The Netherlands
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49
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Gut Microbiome and Organ Fibrosis. Nutrients 2022; 14:nu14020352. [PMID: 35057530 PMCID: PMC8781069 DOI: 10.3390/nu14020352] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/07/2022] [Accepted: 01/08/2022] [Indexed: 02/07/2023] Open
Abstract
Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.
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50
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Faccioli J, Gioia S, Nardelli S, Riggio O, Ridola L. Lactulose in Liver Cirrhosis. PHARMACOTHERAPY FOR LIVER CIRRHOSIS AND ITS COMPLICATIONS 2022:223-240. [DOI: 10.1007/978-981-19-2615-0_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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