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Li Y, Wu YT, Wu H. Management of hepatic encephalopathy following transjugular intrahepatic portosystemic shunts: Current strategies and future directions. World J Gastroenterol 2025; 31:103512. [PMID: 40309228 PMCID: PMC12038546 DOI: 10.3748/wjg.v31.i15.103512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 03/04/2025] [Accepted: 04/02/2025] [Indexed: 04/18/2025] Open
Abstract
Transjugular intrahepatic portosystemic shunts (TIPSs) are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis. However, hepatic encephalopathy (HE), which impairs neuropsychiatric function and motor control, remains the primary adverse effect of TIPS, limiting its utility. Prompt prevention and treatment of post-TIPS HE are critical, as they are strongly associated with readmission rates and poor quality of life. This review focuses on the main pathophysiological mechanisms underlying post-TIPS HE, explores advanced biomarkers and predictive tools, and discusses current management strategies and future directions to prevent or reverse HE following TIPS. These strategies include preoperative patient assessment, individualized shunt diameter optimization, spontaneous portosystemic shunt embolization during the TIPS procedure, postoperative preventive and therapeutic measures such as nutrition management, medical therapy, fecal microbiota transplantation, and stent reduction.
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Affiliation(s)
- Ying Li
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Tong Wu
- Chongqing Medical University-University of Leicester Joint Institute, Chongqing Medical University, Chongqing 400016, China
| | - Hao Wu
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Bai Z, Li C, Lai Y, Hu X, Shi L, Guan X, Xu Y. Role of Rifaximin in the Prognosis of Critically Ill Patients with Liver Cirrhosis. Antibiotics (Basel) 2025; 14:287. [PMID: 40149098 PMCID: PMC11939653 DOI: 10.3390/antibiotics14030287] [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: 02/17/2025] [Revised: 03/05/2025] [Accepted: 03/08/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: Critically ill patients with liver cirrhosis impose a substantial health burden on the world. Rifaximin is a potential treatment option for such patients. Methods: We extracted critically ill patients with liver cirrhosis from the Medical Information Mart for Intensive Care (MIMIC) IV database. Based on study outcomes, the current study included prevention and treatment cohorts. A 1:1 propensity score matching (PSM) analysis was performed to match the characteristics of patients. The risk of ICU admission and intensive care unit (ICU), in-hospital, 90-day, and 180-day death were explored. Cox regression analyses were conducted, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Kaplan-Meier curves were further drawn to demonstrate the cumulative 90-day and 180-day survival rate. Results: Overall, 5381 critically ill patients with liver cirrhosis were included. In the prevention cohort, rifaximin could decrease the risk of ICU admission (HR = 0.427, 95%CI: 0.338-0.539, p < 0.001). In the treatment cohort, rifaximin could decrease the risk of ICU (HR = 0.530, 95%CI: 0.311-0.902, p = 0.019) and in-hospital death (HR = 0.119, 95%CI: 0.033-0.429, p = 0.001) in critically ill patients with liver cirrhosis. However, rifaximin could not decrease the risk of 90-day (HR = 0.905, 95%CI: 0.658-1.245, p = 0.541) and 180-day (HR = 1.043, 95%CI: 0.804-1.353, p = 0.751) death in critically ill patients with liver cirrhosis. Kaplan-Meier curve analyses also showed that rifaximin could not significantly decrease the 90-day (p = 0.570) and 180-day (p = 0.800) cumulative mortality. Conclusions: This study suggests that rifaximin can significantly decrease the risk of ICU admission and improve short-term survival but does not impact long-term survival in critically ill patients with liver cirrhosis.
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Affiliation(s)
- Zhaohui Bai
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; (Z.B.); (Y.L.); (L.S.)
| | - Congcong Li
- Department of Respiratory and Critical Care Medicine, General Hospital of Northern Theater Command, Shenyang 110840, China;
| | - Yongjie Lai
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; (Z.B.); (Y.L.); (L.S.)
| | - Xiaojuan Hu
- Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110016, China;
| | - Luwen Shi
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; (Z.B.); (Y.L.); (L.S.)
| | - Xiaodong Guan
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; (Z.B.); (Y.L.); (L.S.)
| | - Yang Xu
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; (Z.B.); (Y.L.); (L.S.)
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Menestrina L, Parrondo-Pizarro R, Gómez I, Garcia-Serna R, Boyer S, Mestres J. Refined ADME Profiles for ATC Drug Classes. Pharmaceutics 2025; 17:308. [PMID: 40142973 PMCID: PMC11944659 DOI: 10.3390/pharmaceutics17030308] [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: 11/18/2024] [Revised: 02/18/2025] [Accepted: 02/26/2025] [Indexed: 03/28/2025] Open
Abstract
Background: Modern generative chemistry initiatives aim to produce potent and selective novel synthetically feasible molecules with suitable pharmacokinetic properties. General ranges of physicochemical properties relevant for the absorption, distribution, metabolism, and excretion (ADME) of drugs have been used for decades. However, the therapeutic indication, dosing route, and pharmacodynamic response of the individual drug discovery program may ultimately define a distinct desired property profile. Methods: A methodological pipeline to build and validate machine learning (ML) models on physicochemical and ADME properties of small molecules is introduced. Results: The analysis of publicly available data on several ADME properties presented in this work reveals significant differences in the property value distributions across the various levels of the anatomical, therapeutic, and chemical (ATC) drug classification. For most properties, the predicted data distributions agree well with the corresponding distributions derived from experimental data across fourteen drug classes. Conclusions: The refined ADME profiles for ATC drug classes should be useful to guide the de novo generation of advanced lead structures directed toward specific therapeutic indications.
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Affiliation(s)
- Luca Menestrina
- Chemotargets SL, Parc Cientific de Barcelona, Baldiri Reixac 4 (TR-03), 08028 Barcelona, Catalonia, Spain
| | - Raquel Parrondo-Pizarro
- Chemotargets SL, Parc Cientific de Barcelona, Baldiri Reixac 4 (TR-03), 08028 Barcelona, Catalonia, Spain
- Institut de Quimica Computacional i Catalisi, Facultat de Ciencies, Universitat de Girona, Maria Aurelia Capmany 69, 17003 Girona, Catalonia, Spain
| | - Ismael Gómez
- Chemotargets SL, Parc Cientific de Barcelona, Baldiri Reixac 4 (TR-03), 08028 Barcelona, Catalonia, Spain
| | - Ricard Garcia-Serna
- Chemotargets SL, Parc Cientific de Barcelona, Baldiri Reixac 4 (TR-03), 08028 Barcelona, Catalonia, Spain
| | - Scott Boyer
- Chemotargets SL, Parc Cientific de Barcelona, Baldiri Reixac 4 (TR-03), 08028 Barcelona, Catalonia, Spain
| | - Jordi Mestres
- Chemotargets SL, Parc Cientific de Barcelona, Baldiri Reixac 4 (TR-03), 08028 Barcelona, Catalonia, Spain
- Institut de Quimica Computacional i Catalisi, Facultat de Ciencies, Universitat de Girona, Maria Aurelia Capmany 69, 17003 Girona, Catalonia, Spain
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Salaria K, Bhat YM, Banday I, Haq MF, Bhat GA, Parray FQ, Banday M. Optimizing Preoperative Care: Comparing Mechanical Bowel Preparation Alone Versus Combined Oral Antibiotics in Colorectal Cancer Surgery. Indian J Surg Oncol 2025. [DOI: 10.1007/s13193-024-02182-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 12/27/2024] [Indexed: 01/18/2025] Open
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Song DS, Yang JM, Jung YK, Yim HJ, Kim HY, Kim CW, Kim SS, Cheong JY, Lee HL, Lee SW, Yoo JJ, Kim SG, Kim YS. Rifaximin treatment in patients with severe alcoholic hepatitis: A multicenter, randomized controlled, open-label, pilot trial. Ann Hepatol 2024; 30:101749. [PMID: 39662593 DOI: 10.1016/j.aohep.2024.101749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/10/2024] [Accepted: 09/30/2024] [Indexed: 12/13/2024]
Abstract
INTRODUCTION AND OBJECTIVES The short-term mortality of severe alcoholic-associated hepatitis (SAH) is high, but there are no effective treatments to improve short-term mortality other than corticosteroids. This study investigated the effects of adding rifaximin to standard treatment in patients with SAH. MATERIAL AND METHODS In this randomized controlled open-label trial, patients with SAH (Maddrey's discriminant function≥32) were randomized to the rifaximin or control group. Patients were simultaneously treated with corticosteroid or pentoxifylline as standard treatment for 4 weeks. Randomization was stratified by SAH treatment. RESULTS A total of 50 patients were enrolled in this study (29 in the control group and 21 in the rifaximin group). The mean Model for End-stage Liver Disease (MELD) scores were 24.4 and 27.5 in the control and rifaximin groups, respectively (P = 0.106). There were no significant differences in 6-month Liver Transplantation (LT)-free survival rate between the two groups (P = 0.502). When stratified by SAH treatment, there was no significant difference in 6-month LT-free survival rate between the control and rifaximin treatment groups (P = 0.186 in the corticosteroid group and P = 0.548 in the pentoxifylline group). There were no significant differences in the occurrence of liver-related complications between the two groups (all Ps>0.05). The MELD score was the only independent factor for 6-month LT-free survival (hazard ratio 1.188, 95 % confidence interval 1.094-1.289, P<0.001), and rifaximin was not. CONCLUSIONS In patients with SAH, adding rifaximin to corticosteroid or pentoxifylline had no survival benefit and no preventive effect on the development of liver-related complications. The MELD score was the only significant factor for short-term mortality. CLINICAL TRIAL REGISTRATION The study was registered on ClinicalTrials.gov (number: NCT02485106).
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Affiliation(s)
- Do Seon Song
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Jin Mo Yang
- Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Young Kul Jung
- Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, South Korea.
| | - Hyung Joon Yim
- Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, South Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Chang Wook Kim
- Department of Internal Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Soon Sun Kim
- Department of Internal Medicine, Ajou University School of Medicine, Suwon, South Korea
| | - Jae Youn Cheong
- Department of Internal Medicine, Ajou University School of Medicine, Suwon, South Korea
| | - Hae Lim Lee
- Department of Internal Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Sung Won Lee
- Department of Internal Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Bucheon Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Bucheon Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea
| | - Young Seok Kim
- Department of Internal Medicine, Bucheon Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea
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Al-Naimi MS, Abu-Raghif AR, Fawzi HA. Novel therapeutic effects of rifaximin in combination with methylprednisolone for LPS-induced oxidative stress and inflammation in mice: An in vivo study. Toxicol Rep 2024; 13:101808. [PMID: 39640902 PMCID: PMC11617758 DOI: 10.1016/j.toxrep.2024.101808] [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: 09/09/2024] [Revised: 11/08/2024] [Accepted: 11/09/2024] [Indexed: 12/07/2024] Open
Abstract
Cytokine-releasing syndrome (CRS) is a special form of systemic inflammatory response syndrome provoked by factors like viral infections and certain immunomodulatory drugs. To elucidate the potential role of rifaximin (RIF) and its combination with methylprednisolone (MP) against the development and progression of CRS in mice. This experiment consists of two parts: protective and therapeutic interventions. The protective experiment: in the induction group, mice received an intraperitoneal injection (IP) of 5 mg/kg lipopolysaccharide (LPS) without intervention. The other group received various drugs before the induction by three days, then observed for an additional two days (50 mg/kg MP, 50 mg/kg RIF, and a combination of 25 mg/kg RIF with 25 mg/kg MP. The second part of the study involves the therapeutic potential; all groups received similar doses of drugs to that received in the prevention groups, except LPS induction was given first, and after one hour, the mice received daily doses of the drugs for five days. At the end of the experiment, blood and tissue samples were obtained. Mice treated with RIF and its combination with MP showed improved serum TNF-α, IL-6, IL-8, IL-1β, INF-γ, MDA, and GSH in both prevention and therapeutic groups. Histopathologically, mice treated with rifaximin and its combination with MP ameliorates the tissue damage in both lung and liver tissues following LPS induction. In conclusion, rifaximin showed protective and therapeutic effects in LPS-induced cytokine storms in mice through anti-inflammatory and antioxidant mechanisms, and its combination with methylprednisolone showed additive/ synergistic action.
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Affiliation(s)
- Marwa Salih Al-Naimi
- Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq
- Department of Pharmacology and Toxicology, College of Pharmacy, Al-Farahidi University, Baghdad, Iraq
| | - Ahmed R. Abu-Raghif
- Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq
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Cigerim L, Orhan ZD, Kaplan V, Cigerim SC, Feslihan E. Evaluation of the efficacy of topical rifamycin application on postoperative complications after lower impacted wisdom teeth surgery. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2024; 125:101501. [PMID: 37178873 DOI: 10.1016/j.jormas.2023.101501] [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: 03/22/2023] [Revised: 05/07/2023] [Accepted: 05/10/2023] [Indexed: 05/15/2023]
Abstract
PURPOSE This study aimed to evaluate the efficacy of a single-dose topical rifamycin application on postoperative complications after impacted lower third molar surgery. MATERIALS AND METHODS This prospective, controlled clinical study consisted of individuals with bilaterally impacted lower third molars that would be extracted for orthodontic reasons. The extraction sockets were irrigated with 3 ml/250 mg of rifamycin solution in Group 1, while in Group 2 (control group) the extraction sockets were irrigated with 20 ml of physiological saline. Pain intensity was measured daily for 7 days by using visual analog scale. Trismus and edema were evaluated preoperatively and on the postoperative days 2 and 7 by calculating the proportional changes in maximum mouth opening and mean distance between reference points of the face, respectively. Paired samples t-test, Wilcoxon signed rank test and Chi-square test were used to analyze the study variables. RESULTS 35 patients (19 female, 16 male) were included in the study. The mean age of all participants was 22.19±4.98. Alveolitis was observed in 8 patients, (6 in the control group, 2 in the rifamycin group). There was no statistically significant difference between groups in terms of trismus and swelling measurements on the 2nd and 7th postoperative days (p>0.05). VAS scores were significantly low in rifamycin group on postoperative days 1 and 4 (p<0.05). CONCLUSION Within the limits of the present study, topical rifamycin application reduced the incidence of alveolitis, prevented infection, and provided analgesic effect after surgical removal of impacted third molars.
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Affiliation(s)
- Levent Cigerim
- Associate Professor, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Van Yuzuncu Yil University, Van, Turkey
| | - Zeynep Dilan Orhan
- Assistant Professor, Department of Oral and Maxillofacial Surgery, Van Yuzuncu Yil University, Faculty of Dentistry, Van, Turkey
| | - Volkan Kaplan
- Associate Professor, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Tekirdag Namik Kemal University, Tekirdag, Turkey
| | - Saadet Cinarsoy Cigerim
- Assistant Professor, Faculty of Dentistry, Department of Orthodontics, Van Yuzuncu Yil University, Van, Turkey
| | - Erkan Feslihan
- Assistant Professor, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Tekirdag Namik Kemal University, Tekirdag 59030, Turkey.
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Gatta L, Bellini M, Scarpignato C, Marrocco W, Chiriatti A, Grosso A, Lambiase C, Usai-Satta P, Vassallo R, Bartoletti P, Monica F, Manta R, Scotti S, Soncini M. Rifaximin in diverticulosis and diverticular disease: a national survey among Italian gastroenterologists and general practitioners. Intern Emerg Med 2024; 19:1675-1685. [PMID: 38850356 DOI: 10.1007/s11739-024-03669-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 03/26/2024] [Indexed: 06/10/2024]
Abstract
The management of patients with diverticular disease remains challenging. The aim of this national survey was to assess how gastroenterologists and general practitioners use rifaximin to manage diverticulosis and diverticular disease. Members of the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) and the Italian Federation of General Practitioners (FIMMG) were invited to complete a 39-item online survey concerning the use of rifaximin in five clinical settings: (1) diverticulosis; (2) reducing symptoms in symptomatic uncomplicated diverticular disease; (3) reducing the occurrence of diverticulitis in patients with symptomatic uncomplicated diverticular disease (primary prevention); (4) reducing the recurrence of diverticulitis in patients with previous attacks of diverticulitis (secondary prevention); (5) treatment of uncomplicated acute diverticulitis. A total of 1094 physicians completed the survey. Overall, 25.1%, 83.5%, 68%, 74.2%, and 63% of physicians prescribed rifaximin for the clinical settings 1, 2, 3, 4, and 5, respectively. In each clinical setting, the dosage of rifaximin most frequently used was 800 mg/day, the most common duration of therapy was 7 days, and the cyclic administration of treatment (expressed in months) most frequently used was > 24 months. These results highlight that a reappraisal of the use of rifaximin in patients with diverticulosis and diverticular disease is required to reduce the gap between the evidence available and the daily clinical practice, optimizing also the use of healthcare resources.
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Affiliation(s)
- Luigi Gatta
- Gastroenterology Unit, ASL Toscana Nord-Ovest, Versilia Hospital, 55041, Lido di Camaiore, Italy.
| | - Massimo Bellini
- Gastrointestinal Unit, Department of Translational Sciences and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | | | - Walter Marrocco
- Primary Care Physician Azienda Sanitaria Locale (ASL), Roma 5, Tivoli, Rome, Italy
| | - Alberto Chiriatti
- Primary Care Physician Azienda Sanitaria Locale (ASL), Roma 3, Rome, Italy
| | - Antonio Grosso
- Gastrointestinal Unit, Department of Translational Sciences and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Christian Lambiase
- Gastrointestinal Unit, Department of Translational Sciences and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | | | - Roberto Vassallo
- Gastroenterology and Endoscopy Unit, Buccheri la Ferla Hospital, Palermo, Italy
| | | | - Fabio Monica
- Gastroenterology and Digestive Endoscopy Unit, Academic Hospital Cattinara, Trieste, Italy
| | - Raffaele Manta
- Digestive Endoscopy Unit, ASL Toscana Nord-Ovest, "Spedali Riuniti" Hospital, Livorno, Italy
| | - Silvestro Scotti
- Primary Care Physician Azienda Sanitaria Locale (ASL), Napoli 1, Naples, Italy
| | - Marco Soncini
- Department of Internal Medicine, "A. Manzoni" Hospital, Lecco, Italy
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Mares CR, Săsăran MO, Mărginean CO. The relationship between small intestinal bacterial overgrowth and constipation in children - a comprehensive review. Front Cell Infect Microbiol 2024; 14:1431660. [PMID: 38994003 PMCID: PMC11236546 DOI: 10.3389/fcimb.2024.1431660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 06/12/2024] [Indexed: 07/13/2024] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the bacterial population of the small intestine due to an imbalance between the amount of bacteria and the intestinal barrier. Pediatric SIBO presents with a wide spectrum of symptoms, ranging from mild gastrointestinal complaints to malabsorption or malnutrition. Breath tests are commonly used as noninvasive diagnostic tools for SIBO, but a standardized methodology is currently unavailable. Intestinal flora produces methane which slows intestinal transit and increases the contractile activity of small intestine. Emerging literature suggests a correlation between overgrowth of methanogenic bacteria in the intestines and constipation. Treatment of SIBO involves administration of antibacterial therapy in addition to management of underlying conditions and optimal dietary adjustments. However, research on antibiotic treatment for pediatric patients with constipation and SIBO is limited and has yielded conflicting results. In the current review, we summarize the state-of-the-art of the field and discuss previous treatment attempts and currently used regimens for SIBO patients with constipation, with a focus on pediatric populations.
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Affiliation(s)
- Cristina Roxana Mares
- Department of Pediatrics, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mures, Târgu Mures, Romania
| | - Maria Oana Săsăran
- Department of Pediatrics 3, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mures, Târgu Mures, Romania
| | - Cristina Oana Mărginean
- Department of Pediatrics 1, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mures, Târgu Mures, Romania
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Princiotto S, Casciaro B, G Temprano A, Musso L, Sacchi F, Loffredo MR, Cappiello F, Sacco F, Raponi G, Fernandez VP, Iucci T, Mangoni ML, Mori M, Dallavalle S, Pisano C. The antimicrobial potential of adarotene derivatives against Staphylococcus aureus strains. Bioorg Chem 2024; 145:107227. [PMID: 38387400 DOI: 10.1016/j.bioorg.2024.107227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 02/13/2024] [Accepted: 02/16/2024] [Indexed: 02/24/2024]
Abstract
Multidrug-resistant (MDR) pathogens are severely impacting our ability to successfully treat common infections. Here we report the synthesis of a panel of adarotene-related retinoids showing potent antimicrobial activity on Staphylococcus aureus strains (including multidrug-resistant ones). Fluorescence and molecular dynamic studies confirmed that the adarotene analogues were able to induce conformational changes and disfunctions to the cell membrane, perturbing the permeability of the phospholipid bilayer. Since the major obstacle for developing retinoids is their potential cytotoxicity, a selected candidate was further investigated to evaluate its activity on a panel of human cell lines. The compound was found to be well tolerated, with IC50 5-15-fold higher than the MIC on S. aureus strains. Furthermore, the adarotene analogue had a good pharmacokinetic profile, reaching a plasma concentration of about 6 μM after 0.5 h after administration (150 mg/kg), at least twice the MIC observed against various bacterial strains. Moreover, it was demonstrated that the compound potentiated the growth-inhibitory effect of the poorly bioavailable rifaximin, when used in combination. Overall, the collected data pave the way for the development of synthetic retinoids as potential therapeutics for hard-to-treat infectious diseases caused by antibiotic-resistant Gram-positive pathogens.
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Affiliation(s)
- Salvatore Princiotto
- Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, via Celoria 2, 20133 Milano, Italy
| | - Bruno Casciaro
- Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy
| | - Alvaro G Temprano
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain
| | - Loana Musso
- Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, via Celoria 2, 20133 Milano, Italy
| | - Francesca Sacchi
- Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, via Celoria 2, 20133 Milano, Italy
| | - Maria Rosa Loffredo
- Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy
| | - Floriana Cappiello
- Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy
| | - Federica Sacco
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
| | - Giammarco Raponi
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
| | | | | | - Maria Luisa Mangoni
- Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy
| | - Mattia Mori
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy
| | - Sabrina Dallavalle
- Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, via Celoria 2, 20133 Milano, Italy.
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Yoon SH, Yang IJ, Kim JY, Lee KH. Efficacy of a 1 day Rifaximin and Metronidazole Regimen and Mechanical Bowel Preparation for Preventing Surgical Site Infection in Minimally Invasive Colorectal Cancer Surgery: A Prospective Observational Study. Am Surg 2024; 90:550-559. [PMID: 37707885 DOI: 10.1177/00031348231200667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2023]
Abstract
BACKGROUND A combination of oral antibiotics and mechanical bowel preparation is recommended for patients scheduled to undergo elective colorectal surgery on the basis of recent large trials that have reported the superiority of this approach in preventing surgical site infections (SSIs). However, there are no standard recommendations for this approach. Therefore, in this study, we evaluated the efficacy of rifaximin and metronidazole and mechanical bowel preparation for preventing SSIs in cases of minimally invasive surgery for colorectal cancer. METHODS This single-arm prospective observational study included 256 individuals. The primary end point was the rate of SSI. Rifaximin 400 mg and metronidazole 500 mg were administered twice daily (10 am and 10 pm), and mechanical bowel preparation was administered the day before the operation. RESULTS After excluding 15 patients, 241 were enrolled. No adverse event occurred following the administration of oral antibiotics and mechanical bowel preparation; there was 100% compliance. The total SSI rate was 2.9%; the rates of incisional and organ/space SSIs were 1.2% and 1.7%, respectively. All patients were treated conservatively. Univariate analyses revealed preoperative anemia, hypoalbuminemia, and transfusion and postoperative transfusion were significantly associated with SSIs. DISCUSSION A 1 day rifaximin and metronidazole regimen with mechanical bowel preparation for elective minimally invasive surgery for colorectal cancer was associated with a favorable SSI rate of 2.9%, safety, and high compliance. This approach is appropriate for inclusion in the current guidelines for perioperative management of patients scheduled to undergo minimally invasive surgery for colorectal cancer.
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Affiliation(s)
- Seung-Hwan Yoon
- Department of Colorectal Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - In Jun Yang
- Department of Colorectal Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Ji Yeon Kim
- Department of Colorectal Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Kyung-Ha Lee
- Department of Colorectal Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea
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12
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Huang CH, Amodio P. Can rifaximin for hepatic encephalopathy be discontinued during broad-spectrum antibiotic treatment? World J Hepatol 2024; 16:115-119. [PMID: 38495281 PMCID: PMC10941747 DOI: 10.4254/wjh.v16.i2.115] [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: 11/19/2023] [Revised: 01/03/2024] [Accepted: 01/24/2024] [Indexed: 02/27/2024] Open
Abstract
Hepatic encephalopathy (HE) is a formidable complication in patients with decompensated cirrhosis, often necessitating the administration of rifaximin (RFX) for effective management. RFX, is a gut-restricted, poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE. It has shown notable reductions in infection, hospital readmission, duration of hospital stay, and mortality. However, limited data exist about the concurrent use of RFX with broad-spectrum antibiotics, because the patients are typically excluded from studies assessing RFX efficacy in HE. A pharmacist-driven quasi-experimental pilot study was done to address this gap. They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment, particularly in critically ill patients in intensive care unit (ICU). The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered. The findings also indicate that RFX discontinuation during broad-spectrum antibiotic therapy was not associated with higher rates of delirium or coma, and this result remained robust after adjustment in multivariate analysis. Furthermore, rates of other secondary clinical and safety outcomes, including ICU mortality and 48-hour changes in vasopressor requirements, were comparable. However, since the activity of RFX is mainly confined to the modulation of gut microbiota, its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable, given the overlapping antibiotic activity. Further, this suggests that the action of RFX on HE is class-specific (related to its activity on gut microbiota), rather than drug-specific. A recent double-blind randomized controlled (ARiE) trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics. Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections. Despite these compelling results, both studies have limitations. A prospective, multi-center evaluation of a larger sample, with placebo control, and comprehensive neurologic evaluation of HE is warranted. It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.
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Affiliation(s)
- Chien-Hao Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 333, Taiwan
| | - Piero Amodio
- Department of Clinical and Experimental Medicine, University of Padua, Padova 35122, Italy.
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13
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Gentry EC, Collins SL, Panitchpakdi M, Belda-Ferre P, Stewart AK, Carrillo Terrazas M, Lu HH, Zuffa S, Yan T, Avila-Pacheco J, Plichta DR, Aron AT, Wang M, Jarmusch AK, Hao F, Syrkin-Nikolau M, Vlamakis H, Ananthakrishnan AN, Boland BS, Hemperly A, Vande Casteele N, Gonzalez FJ, Clish CB, Xavier RJ, Chu H, Baker ES, Patterson AD, Knight R, Siegel D, Dorrestein PC. Reverse metabolomics for the discovery of chemical structures from humans. Nature 2024; 626:419-426. [PMID: 38052229 PMCID: PMC10849969 DOI: 10.1038/s41586-023-06906-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 64.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 11/28/2023] [Indexed: 12/07/2023]
Abstract
Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis1,2, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn's disease. Several of these compounds and related structures affected pathways associated with IBD, such as interferon-γ production in CD4+ T cells3 and agonism of the pregnane X receptor4. Culture of bacteria belonging to the Bifidobacterium, Clostridium and Enterococcus genera produced these bile amidates. Because searching repositories with tandem mass spectrometry spectra has only recently become possible, this reverse metabolomics approach can now be used as a general strategy to discover other molecules from human and animal ecosystems.
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Affiliation(s)
- Emily C Gentry
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
- Department of Chemistry, Virginia Tech, Blacksburg, VA, USA
| | - Stephanie L Collins
- Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA
| | - Morgan Panitchpakdi
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
| | - Pedro Belda-Ferre
- Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, Jacobs School of Engineering, University of California, San Diego, San Diego, CA, USA
| | - Allison K Stewart
- Department of Chemistry, North Carolina State University, Raleigh, NC, USA
| | | | - Hsueh-Han Lu
- Department of Pathology, University of California, San Diego, La Jolla, CA, USA
| | - Simone Zuffa
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
| | - Tingting Yan
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | | | | | - Allegra T Aron
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
| | - Mingxun Wang
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
| | - Alan K Jarmusch
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
- Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
| | - Fuhua Hao
- Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, USA
| | - Mashette Syrkin-Nikolau
- Division of Gastroenterology, Department of Pediatrics, Rady Children's Hospital University of California San Diego, La Jolla, CA, USA
| | - Hera Vlamakis
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA
| | | | - Brigid S Boland
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
| | - Amy Hemperly
- Division of Gastroenterology, Department of Pediatrics, Rady Children's Hospital University of California San Diego, La Jolla, CA, USA
| | - Niels Vande Casteele
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
| | - Frank J Gonzalez
- Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Clary B Clish
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Ramnik J Xavier
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Hiutung Chu
- Department of Pathology, University of California, San Diego, La Jolla, CA, USA
- CU-UCSD, Center for Mucosal Immunology, Allergy and Vaccine Development, University of California, San Diego, La Jolla, California, USA
| | - Erin S Baker
- Department of Chemistry, North Carolina State University, Raleigh, NC, USA
- Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Andrew D Patterson
- Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, USA
| | - Rob Knight
- Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, Jacobs School of Engineering, University of California, San Diego, San Diego, CA, USA
- Center for Microbiome Innovation, Jacobs School of Engineering, University of California, San Diego, San Diego, CA, USA
- Department of Bioengineering, University of California, San Diego, San Diego, California, USA
| | - Dionicio Siegel
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
| | - Pieter C Dorrestein
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
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DE Bastiani R, Lopetuso LR, DE Bastiani M, Bacchin P, Benedetto E, Boscariolo L, Caneve R, Chesani F, Chiumeo F, Civic Z, Dainese A, DE Polo M, Disclafani G, Grattagliano I, Mana O, Mancuso M, Mastronuzzi T, Pati A, Pirrotta E, Salandini M, Sanna G, Scoglio R, Severino P, Tosetti C, Turnava L, Zamparella M, Elisei W, Gasbarrini A, Tursi A. Assessment of small intestinal bacterial overgrowth and methane production in patients on chronic proton-pump inhibitor treatment: prevalence and role of rifaximin in its management in primary care. Minerva Gastroenterol (Torino) 2023; 69:523-528. [PMID: 36943203 DOI: 10.23736/s2724-5985.21.03118-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/23/2023]
Abstract
BACKGROUND Although proton pump inhibitor (PPI) drugs have considered able to induce small intestinal bacterial overgrowth (SIBO), no data are so far available from primary care (PC). We assessed the prevalence of SIBO and methane (CH4) production consequent to chronic PPI therapy using Lactulose Breath Test (LBT). Secondary aim was to explore the possible role of rifaximin in treating PPI-induced SIBO patients. METHODS One hundred twenty-five gastroesophageal reflux disease patients, constantly treated with PPI for at least 6 months and undergoing to LBT, were retrospectively assessed. An age-matched control population (control) of 100 patients, which had not used PPI in the last 6 months, was also enrolled. In the PPI group, SIBO positive patients and CH4 producers were treated with rifaximin 1200 mg/daily for 14 days and re-checked with LBT one month after the end of treatment. The area under the curve (AUC) before and after treatment was also calculated for both SIBO positive patients and CH4 producers. RESULTS In the PPI group, SIBO prevalence was significantly higher vs. controls (38/125 [30.4%] vs. 27/100 [27%], P<0.05). 77/125 (61.6%) PPI patients were found to be CH4 producers vs. 21/100 (21%) controls (P<0.05). Among SIBO patients in the PPI group, 34 (89.4%) were also CH4 producers vs. 17/27 (63%) controls (P<0.05). After treatment, LBT resulted negative in 15/22 SIBO patients (68.1%) (P<0.05) and in 18/34 CH4 producers (52.9%) (P<0.05). At the AUC analysis, an overall reduction of 54.2% for H2 in SIBO patients and of 47.7% for CH4 was assessed after rifaximin treatment (P<0.05). CONCLUSIONS Our data showed that chronic use of PPI could be able to increase the prevalence of SIBO and to shift the intestinal microbial composition towards a CH4-producing flora. rifaximin could represent a useful therapeutical option for PPI-induced SIBO and for modulating CH4-producing flora.
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Affiliation(s)
- Rudi DE Bastiani
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Loris R Lopetuso
- Department of Medical and Surgical Sciences, Sacred Heart Catholic University, Rome, Italy
- CEMAD Digestive Disease Center, IRCCS A. Gemelli University Polyclinic Foundation, Rome, Italy
- Department of Medicine and Ageing Sciences, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy
- Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, Chieti, Italy
| | - Marco DE Bastiani
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Paolo Bacchin
- General Pratictioner, Azienda Sanitaria Locale Veneto 1, Santa Giustina, Belluno, Italy
| | - Edoardo Benedetto
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Laura Boscariolo
- General Pratictioner, Azienda Sanitaria Locale Veneto 1, Feltre, Belluno, Italy
| | - Rosanna Caneve
- General Pratictioner, Azienda Sanitaria Locale Veneto 1, Lamon, Belluno, Italy
| | - Fabio Chesani
- General Pratictioner, Azienda Provinciale Socio-Sanitaria Trento, Trento, Italy
| | - Francesco Chiumeo
- General Pratictioner, Azienda Provinciale Socio-Sanitaria Trento, Civezzano, Trento, Italy
| | - Zinaida Civic
- General Pratictioner, Azienda Sanitaria Locale Veneto 1, Feltre, Belluno, Italy
| | - Antonio Dainese
- General Pratictioner, Azienda Provinciale Socio-Sanitaria Trento, Stenico, Trento, Italy
| | - Manuela DE Polo
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Giuseppe Disclafani
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Ignazio Grattagliano
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Ornella Mana
- General Pratictioner, Azienda Provinciale Socio-Sanitaria Trento, Trento, Italy
| | - Maurizio Mancuso
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Tecla Mastronuzzi
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Antonino Pati
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Enzo Pirrotta
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy -
| | - Maurizio Salandini
- General Pratictioner, Azienda Provinciale Socio-Sanitaria Trento, Trento, Italy
| | - Guido Sanna
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Riccardo Scoglio
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Pietro Severino
- General Pratictioner, Azienda Provinciale Socio-Sanitaria Trento, Trento, Italy
| | - Cesare Tosetti
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Leyla Turnava
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Maria Zamparella
- GIGA-CP Italian Association for Primary Care Gastroenterology, Feltre, Belluno, Italy
| | - Walter Elisei
- Division of Gastroenterology, S. Camillo Hospital, Rome, Italy
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Sacred Heart Catholic University, Rome, Italy
| | - Antonio Tursi
- Territorial Gastroenterology Service, Azienda Sanitaria Locale Barletta-Andria-Trani, Andria, Barletta-Andria-Trani, Italy
- Post-graduate School of Digestive Diseases, Department of Medical and Surgical Sciences, Sacred Heart Catholic University, Rome, Italy
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15
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Luo M, Xie P, Deng X, Fan J, Xiong L. Rifaximin Ameliorates Loperamide-Induced Constipation in Rats through the Regulation of Gut Microbiota and Serum Metabolites. Nutrients 2023; 15:4502. [PMID: 37960154 PMCID: PMC10648458 DOI: 10.3390/nu15214502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 10/10/2023] [Accepted: 10/20/2023] [Indexed: 11/15/2023] Open
Abstract
Structural changes in the gut microbiota are closely related to the development of functional constipation, and regulating the gut microbiota can improve constipation. Rifaximin is a poorly absorbed antibiotic beneficial for regulating gut microbiota, but few studies have reported its effects on constipation. The purpose of this study was to investigate the effect of rifaximin on loperamide-induced constipation in SD rats. The results showed that rifaximin improved constipation by increasing serum 5-HT, SP, and the mRNA expression of AQP3, AQP8, and reducing the mRNA expression of TLR2 and TLR4. In addition, rifaximin could regulate the gut microbiota of constipated rats, such as increasing the potentially beneficial bacteria Akkermansia muciniphila and Lactobacillus murinus, reducing the Bifidobacterium pseudolongum. According to metabolomics analysis, many serum metabolites, including bile acids and steroids, were changed in constipated rats and were recovered via rifaximin intervention. In conclusion, rifaximin might improve loperamide-induced constipation in rats by increasing serum excitatory neurotransmitters and neuropeptides, modulating water metabolism, and facilitating intestinal inflammation. Muti-Omics analysis results showed that rifaximin has beneficial regulatory effects on the gut microbiota and serum metabolites in constipated rats, which might play critical roles in alleviating constipation. This study suggests that rifaximin might be a potential strategy for treating constipation.
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Affiliation(s)
| | | | | | | | - Lishou Xiong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; (M.L.); (P.X.); (X.D.); (J.F.)
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16
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Torre A, Córdova-Gallardo J, Frati Munari AC. Rifaximin Alfa and Liver Diseases: More Than a Treatment for Encephalopathy, a Disease Modifier. Ther Clin Risk Manag 2023; 19:839-851. [PMID: 37899985 PMCID: PMC10612522 DOI: 10.2147/tcrm.s425292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 09/17/2023] [Indexed: 10/31/2023] Open
Abstract
RFX, a rifamycin-based antibacterial agent obtained by the culture of the actinomycete Streptomyces mediterranei, has a broad antibacterial spectrum covering gram- positive, gram-negative, aerobic, and anaerobic bacteria. RFX is an antibiotic that elicits its effect by inhibiting bacterial RNA synthesis. When administered orally, its intestinal absorption is extremely low (<0.4%), restricting antibacterial activity mainly in the intestinal tract, with few systemic side effects. RFX has been recommended by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver guidelines for the treatment of HE. RFX may contribute to restore hepatic function and to decrease the development of liver fibrosis. Its efficacy has been shown in patients with previous hepatic encephalopathy and several complications, such as infections, including spontaneous bacterial peritonitis, ascites and oesophageal variceal bleeding. Thus, RFX has an outstanding role in the therapeutic arsenal in hepatic cirrhosis, under the concept of disease modifier.
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Affiliation(s)
- Aldo Torre
- Guest Research, Metabolic Unit Department, Instituto Nacional de Ciencias Médicas Y Nutrición “Salvador Zubirán”, México City, Mexico
- Guest Research, Liver Unit Department, Hospital General de México, México City, Mexico
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17
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Gupta A, Shetty S, Mutalik S, Chandrashekar H R, K N, Mathew EM, Jha A, Mishra B, Rajpurohit S, Ravi G, Saha M, Moorkoth S. Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation. Heliyon 2023; 9:e20406. [PMID: 37810864 PMCID: PMC10550623 DOI: 10.1016/j.heliyon.2023.e20406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 10/10/2023] Open
Abstract
Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. Untreated Helicobacter pylori (H. pylori) infection is one of the major reasons for chronic PUD which, if left untreated, may also result in gastric cancer. Treatment of H. pylori is always a challenge to the treating doctor because of the poor bioavailability of the drug at the inner layers of gastric mucosa where the bacteria resides. This results in ineffective therapy and antibiotic resistance. Current treatment regimens available for gastric ulcer and H. pylori infection uses a combination of multiple antimicrobial agents, proton pump inhibitors (PPIs), H2-receptor antagonists, dual therapy, triple therapy, quadruple therapy and sequential therapy. This polypharmacy approach leads to patient noncompliance during long term therapy. Management of H. pylori induced gastric ulcer is a burning issue that necessitates alternative treatment options. Novel formulation strategies such as extended-release gastro retentive drug delivery systems (GRDDS) and nanoformulations have the potential to overcome the current bioavailability challenges. This review discusses the current status of H. pylori treatment, their limitations and the formulation strategies to overcome these shortcomings. Authors propose here an innovative strategy to improve the H. pylori eradication efficiency.
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Affiliation(s)
- Ashutosh Gupta
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Shiran Shetty
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Srinivas Mutalik
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Raghu Chandrashekar H
- Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Nandakumar K
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Elizabeth Mary Mathew
- School of Pharmacy, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana
| | - Abhishek Jha
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Brahmeshwar Mishra
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, Uttar Pradesh, India
| | - Siddheesh Rajpurohit
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Gundawar Ravi
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Moumita Saha
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Sudheer Moorkoth
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
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18
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Khan Z, Khan SK, Reyaz I, Anam H, Ijaz O, Attique I, Shahzad Z, Saleem F. Effectiveness of Rifaximin on the Outcomes of Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cureus 2023; 15:e44807. [PMID: 37809182 PMCID: PMC10558962 DOI: 10.7759/cureus.44807] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2023] [Indexed: 10/10/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder that impacts the lives of many individuals worldwide. We conducted a systemic review and meta-analysis of randomized controlled trials (RCTs) to assess both the effectiveness of rifaximin in alleviating IBS symptoms and its potential adverse effects. PubMed, Web of Science, Embase, the Cochrane Library, Scopus, and Google Scholar were searched from inception until August 20, 2023, for studies comparing rifaximin with placebo in the resolution of symptoms among IBS patients. Risk ratios (RRs) and their corresponding 95% confidence intervals (CIs) were derived for all the outcomes of interest. Six RCTs were pooled in this analysis. The results showed improved abdominal distension with rifaximin over the control group. Overall symptom relief at the end of the treatment period and follow-up period was also observed in the patients receiving rifaximin. However, no significant differences were found between the rifaximin group and the control group for the outcomes of abdominal pain, nausea, headache, vomiting, diarrhea, sinusitis, bronchitis, and upper respiratory tract infection. The results of our meta-analysis support the use of rifaximin in the treatment of IBS, owing to its safety and effectiveness. Future RCTs should be conducted to assess this topic of interest more extensively.
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Affiliation(s)
- Zarghuna Khan
- Internal Medicine, Rehman Medical Institute, Peshawar, PAK
| | | | - Ibrahim Reyaz
- Internal Medicine, Christian Medical College and Hospital, Ludhiana, IND
| | - Hemalatha Anam
- Internal Medicine, Apollo Institute of Medical Sciences and Research, Hyderabad, IND
| | - Osama Ijaz
- Internal Medicine, Services Institute of Medical Sciences, Lahore, PAK
| | - Ilqa Attique
- Internal Medicine, Foundation University Medical College, Islamabad, PAK
| | - Zoha Shahzad
- Internal Medicine, Fatima Jinnah Medical University, Lahore, PAK
| | - Faraz Saleem
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, Akhtar Saeed Medical and Dental College, Lahore, PAK
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Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev 2023; 7:CD011585. [PMID: 37467180 PMCID: PMC10360160 DOI: 10.1002/14651858.cd011585.pub2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Abstract
BACKGROUND Hepatic encephalopathy describes the spectrum of neuropsychiatric changes that may complicate the course of cirrhosis and detrimentally affect outcomes. Ammonia plays a key role in its development. Rifaximin is a non-absorbable antibiotic that inhibits urease-producing bacteria and reduces absorption of dietary and bacterial ammonia. OBJECTIVES To evaluate the beneficial and harmful effects of rifaximin versus placebo, no intervention, or non-absorbable disaccharides for: (i) the prevention of hepatic encephalopathy, and (ii) the treatment of minimal and overt hepatic encephalopathy, in people with cirrhosis, both when used alone and when combined with a non-absorbable disaccharide. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Clinical Trials Register, CENTRAL, MEDLINE, Embase, three other databases, the reference lists of identified papers, and relevant conference proceedings. We wrote to authors and pharmaceutical companies for information on other published, unpublished, or ongoing trials. Searches were performed to January 2023. SELECTION CRITERIA We included randomised clinical trials assessing prevention or treatment of hepatic encephalopathy with rifaximin alone, or with a non-absorbable disaccharide, versus placebo/no intervention, or a non-absorbable disaccharide alone. DATA COLLECTION AND ANALYSIS Six authors independently searched for studies, extracted data, and validated findings. We assessed the design, bias risk, and participant/intervention characteristics of the included studies. We assessed mortality, serious adverse events, health-related quality of life, hepatic encephalopathy, non-serious adverse events, blood ammonia, Number Connection Test-A, and length of hospital stay. MAIN RESULTS We included 41 trials involving 4545 people with, or at risk for, developing hepatic encephalopathy. We excluded 89 trials and identified 13 ongoing studies. Some trials involved participants with more than one type of hepatic encephalopathy or more than one treatment comparison. Hepatic encephalopathy was classed as acute (13 trials), chronic (7 trials), or minimal (8 trials), or else participants were considered at risk for its development (13 trials). The control groups received placebo (12 trials), no/standard treatment (1 trial), or a non-absorbable disaccharide (14 trials). Eighteen trials assessed rifaximin plus a non-absorbable disaccharide versus a non-absorbable disaccharide alone. We classified 11 trials as at high risk of overall bias for mortality and 28 for non-mortality outcomes, mainly due to lack of blinding, incomplete outcome data, and selective reporting. Compared to placebo/no intervention, rifaximin likely has no overall effect on mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.50 to 1.38; P = 48, I2 = 0%; 13 trials, 1007 participants; moderate-certainty evidence), and there may be no overall effect when compared to non-absorbable disaccharides (RR 0.99, 95% CI 0.49 to 1.97; P = 0.97, I2 = 0%; 10 trials, 786 participants; low-certainty evidence). However, there is likely a reduction in the overall risk of mortality when comparing rifaximin plus a non-absorbable disaccharide to a non-absorbable disaccharide alone (RR 0.69, 95% CI 0.55 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) = 22; P = 0.001, I2 = 0%; 14 trials, 1946 participants; moderate-certainty evidence). There is likely no effect on the overall risk of serious adverse events when comparing rifaximin to placebo/no intervention (RR 1.05, 95% CI 0.83 to 1.32; P = 68, I2 = 0%; 9 trials, 801 participants; moderate-certainty evidence) and there may be no overall effect when compared to non-absorbable disaccharides (RR 0.97, 95% CI 0.66 to 1.40; P = 85, I2 = 0%; 8 trials, 681 participants; low-certainty evidence). However, there was very low-certainty evidence that use of rifaximin plus a non-absorbable disaccharide may be associated with a lower risk of serious adverse events than use of a non-absorbable disaccharide alone (RR 0.66, 95% CI 0.45 to 0.98; P = 0.04, I2 = 60%; 7 trials, 1076 participants). Rifaximin likely results in an overall effect on health-related quality of life when compared to placebo/no intervention (mean difference (MD) -1.43, 95% CI -2.87 to 0.02; P = 0.05, I2 = 81%; 4 trials, 214 participants; moderate-certainty evidence), and may benefit health-related quality of life in people with minimal hepatic encephalopathy (MD -2.07, 95% CI -2.79 to -1.35; P < 0.001, I2 = 0%; 3 trials, 176 participants). The overall effect on health-related quality of life when comparing rifaximin to non-absorbable disaccharides is very uncertain (MD -0.33, 95% CI -1.65 to 0.98; P = 0.62, I2 = 0%; 2 trials, 249 participants; very low-certainty evidence). None of the combined rifaximin/non-absorbable disaccharide trials reported on this outcome. There is likely an overall beneficial effect on hepatic encephalopathy when comparing rifaximin to placebo/no intervention (RR 0.56, 95% CI 0.42 to 0.77; NNTB = 5; P < 0.001, I2 = 68%; 13 trials, 1009 participants; moderate-certainty evidence). This effect may be more marked in people with minimal hepatic encephalopathy (RR 0.40, 95% CI 0.31 to 0.52; NNTB = 3; P < 0.001, I2 = 10%; 6 trials, 364 participants) and in prevention trials (RR 0.71, 95% CI 0.56 to 0.91; NNTB = 10; P = 0.007, I2 = 36%; 4 trials, 474 participants). There may be little overall effect on hepatic encephalopathy when comparing rifaximin to non-absorbable disaccharides (RR 0.85, 95% CI 0.69 to 1.05; P = 0.13, I2 = 0%; 13 trials, 921 participants; low-certainty evidence). However, there may be an overall beneficial effect on hepatic encephalopathy when comparing rifaximin plus a non-absorbable disaccharide to a non-absorbable disaccharide alone (RR 0.58, 95% CI 0.48 to 0.71; NNTB = 5; P < 0.001, I2 = 62%; 17 trials, 2332 participants; low-certainty evidence). AUTHORS' CONCLUSIONS Compared to placebo/no intervention, rifaximin likely improves health-related quality of life in people with minimal hepatic encephalopathy, and may improve hepatic encephalopathy, particularly in populations with minimal hepatic encephalopathy and when it is used for prevention. Rifaximin likely has no overall effect on mortality, serious adverse events, health-related quality of life, or hepatic encephalopathy compared to non-absorbable disaccharides. However, when used in combination with a non-absorbable disaccharide, it likely reduces overall mortality risk, the risk of serious adverse events, improves hepatic encephalopathy, reduces the length of hospital stay, and prevents the occurrence/recurrence of hepatic encephalopathy. The certainty of evidence for these outcomes is very low to moderate; further high-quality trials are needed.
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Affiliation(s)
- Harry D Zacharias
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
| | - Fady Kamel
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
| | - Jaclyn Tan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
| | - Nina Kimer
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Lise Lotte Gluud
- Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Marsha Y Morgan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
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Di Vincenzo F, Nicoletti A, Negri M, Vitale F, Zileri Dal Verme L, Gasbarrini A, Ponziani FR, Cerrito L. Gut Microbiota and Antibiotic Treatments for the Main Non-Oncologic Hepato-Biliary-Pancreatic Disorders. Antibiotics (Basel) 2023; 12:1068. [PMID: 37370387 DOI: 10.3390/antibiotics12061068] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/10/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
The gut microbiota is a pivotal actor in the maintenance of the balance in the complex interconnections of hepato-biliary-pancreatic system. It has both metabolic and immunologic functions, with an influence on the homeostasis of the whole organism and on the pathogenesis of a wide range of diseases, from non-neoplastic ones to tumorigenesis. The continuous bidirectional metabolic communication between gut and hepato-pancreatic district, through bile ducts and portal vein, leads to a continuous interaction with translocated bacteria and their products. Chronic liver disease and pancreatic disorders can lead to reduced intestinal motility, decreased bile acid synthesis and intestinal immune dysfunction, determining a compositional and functional imbalance in gut microbiota (dysbiosis), with potentially harmful consequences on the host's health. The modulation of the gut microbiota by antibiotics represents a pioneering challenge with striking future therapeutic opportunities, even in non-infectious diseases. In this setting, antibiotics are aimed at harmonizing gut microbial function and, sometimes, composition. A more targeted and specific approach should be the goal to pursue in the future, tailoring the treatment according to the type of microbiota modulation to be achieved and using combined strategies.
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Affiliation(s)
- Federica Di Vincenzo
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Alberto Nicoletti
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Marcantonio Negri
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Federica Vitale
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Lorenzo Zileri Dal Verme
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, 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, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Lucia Cerrito
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
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Koch M, Maraolo AE, Natoli G, Corrao S. Preventing acute diverticulitis. any roles for non-absorbable antibiotics? in search of evidence: a systematic review, meta-analysis, and trial sequential analysis. FRONTIERS IN GASTROENTEROLOGY 2023; 2. [DOI: 10.3389/fgstr.2023.1170271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
BackgroundHospital admissions for diverticulitis, a complication of diverticular disease, are very much on the increase. Prevention of diverticulitis could cut costs and save lives.AimsTo identify whether the risk of the first episode of diverticulitis (primary prevention) or recurrence of diverticulitis (secondary prevention) can be reduced in patients with diverticular disease using non-absorbable antibiotics (mainly rifaximin).MethodsThe studies were identified by searching PubMed and CENTRAL from 1990 to May 2022. The methodological quality of each study was also evaluated. The outcome of the meta-analysis was the occurrence of a first or subsequent episode of diverticulitis. In addition, a trial sequential analysis was performed to evaluate whether the results would be subject to type I or type II errors.ResultsPrimary prevention: the risk difference was statistically significant in favor of rifaximin (-0,019, or -1.9%, CI -0,6 to -3,3%). There was no evidence of heterogeneity (I2 0%). At one year, two years, and eight years of age, the NNT was 62, 52, and 42, respectively. The level of evidence had a moderate degree of certainty. Secondary prevention: the risk difference was statistically significant in favor of rifaximin (- 0,24, or -24%, CI -47 to -2%). There was evidence of heterogeneity (I2 92%); NNT resulted in 5. The grade level was low.ConclusionsRifaximin can lower the risk of a first episode of diverticulitis. However, the cost-benefit ratio currently appears too high. Rifaximin could also reduce the risk of a second episode, but the quality of the evidence is low.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022379258.
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Rashidi-Alavijeh J, Nuruzade N, Frey A, Huessler EM, Hörster A, Zeller AC, Schütte A, Schmidt H, Willuweit K, Lange CM. Implications of anaemia and response to anaemia treatment on outcomes in patients with cirrhosis. JHEP Rep 2023; 5:100688. [PMID: 36926273 PMCID: PMC10011825 DOI: 10.1016/j.jhepr.2023.100688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 12/29/2022] [Accepted: 01/12/2023] [Indexed: 01/30/2023] Open
Abstract
Background & Aims Anaemia is frequently observed in patients with cirrhosis and was identified as a predictor of adverse outcomes, such as increased mortality and occurrence of acute-on-chronic liver failure. To date, the possible effects of iron supplementation on these adverse outcomes are not well described. We therefore aimed to assess the role of iron supplementation in patients with cirrhosis and its capability to improve prognosis. Methods Laboratory diagnostics were performed in consecutive outpatients with cirrhosis admitted between July 2018 and December 2019 to the University Hospital Essen. Associations with transplant-free survival were assessed in regression models. Results A total of 317 outpatients with cirrhosis were included, of whom 61 received a liver transplant (n = 19) or died (n = 42). In multivariate Cox regression analysis, male sex (hazard ratio [HR] = 3.33, 95% CI [1.59, 6.99], p = 0.001), model for end-stage liver disease score (HR = 1.19, 95% CI [1.11, 1.27], p <0.001) and the increase of haemoglobin levels within 6 months (ΔHb6) (HR = 0.72, 95% CI [0.63, 0.83], p <0.001) were associated with transplant-free survival. Regarding the prediction of haemoglobin increase, intake of rifaximin (beta = 0.50, SD beta = 0.19, p = 0.007) and iron supplementation (beta = 0.79, SD beta = 0.26, p = 0.003) were significant predictors in multivariate analysis. Conclusions An increase of haemoglobin levels is associated with improvement of transplant-free survival in patients with cirrhosis. Because the prediction of haemoglobin increase significantly depends on rifaximin and iron supplementation, application of these two medications can have an important impact on the outcome of these patients. Impact and implications Anaemia is very common in patients with cirrhosis and is known to be a predictor of negative outcomes, but little is known about the effect of iron substitution in these individuals. In our cohort, increase of haemoglobin levels improved transplant-free survival of patients with cirrhosis. The increase of haemoglobin levels was mainly induced by iron supplementation and was even stronger in the case of concomitant use of iron and rifaximin. Clinical trial registration UME-ID-10042.
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Key Words
- ACLF, acute-on-chronic liver failure
- AIH, autoimmune hepatitis
- ALT, alanine aminotransferase
- AP, alkaline phosphatase
- AST, aspartate aminotransferase
- CRP, C-reactive protein
- Haemoglobin
- INR, international normalised ratio
- Iron deficiency
- Iron supplementation
- LT, liver transplantation
- Liver transplantation
- MELD, model for end-stage liver disease
- NASH, non-alcoholic steatohepatitis
- NSBBs, non-selective beta blockers
- PBC, primary biliary cholangitis
- PSC, primary sclerosing cholangitis
- Rifaximin
- SSC, secondary sclerosing cholangitis
- TIPS, transjugular intrahepatic portosystemic shunt
- aPTT, activated partial thromboplastin time
- ΔHb3, difference of haemoglobin levels after 3 months
- ΔHb6, difference of haemoglobin levels after 6 months
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Affiliation(s)
- Jassin Rashidi-Alavijeh
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Nargiz Nuruzade
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Alexandra Frey
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Eva-Maria Huessler
- Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Duisburg, Germany
| | - Anne Hörster
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Amos Cornelius Zeller
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Andreas Schütte
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Hartmut Schmidt
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Katharina Willuweit
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
| | - Christian Markus Lange
- Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Duisburg, Germany
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Ikeuchi K, Tsutsumi T, Ishizaka A, Mizutani T, Sedohara A, Koga M, Tamaoki S, Yotsuyanagi H. Modulation of duodenal and jejunal microbiota by rifaximin in mice with CCl 4-induced liver fibrosis. Gut Pathog 2023; 15:14. [PMID: 36945059 PMCID: PMC10029291 DOI: 10.1186/s13099-023-00541-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 03/07/2023] [Indexed: 03/23/2023] Open
Abstract
BACKGROUND Rifaximin is a poorly absorbed broad-spectrum antibiotic used for hepatic encephalopathy. Although increased Lactobacillaceae and decreased Bacteroidetes abundance are characteristic of hepatic encephalopathy, rifaximin does not dramatically alter the stool microbiota. As the antimicrobial effect of rifaximin increases by micellization with bile acids, we hypothesized that rifaximin alters the microbiota in the duodenum and jejunum, where the levels of bile acids are abundant. METHODS AND RESULTS Eight-week-old BALB/c mice were injected with carbon tetrachloride (CCl4) intraperitoneally for 12 weeks to induce liver fibrosis. The mice were grouped into the control (n = 9), CCl4 (n = 13), and rifaximin group in which mice were treated with rifaximin for two weeks after CCl4 administration (n = 13). We analyzed the microbiota of the duodenum, jejunum, ileum, cecum, and stool using 16S ribosomal RNA gene analysis. The content of Lactobacillaceae, the most abundant bacterial family in the duodenum and small intestine, increased in the CCl4 group, especially in the jejunum (median 67.0% vs 87.8%, p = 0.03). Rifaximin significantly decreased Lactobacillaceae content in the duodenum (median 79.4% vs 19.0%, p = 0.006) and jejunum (median 87.8% vs 61.3%, p = 0.03), but not in the ileum, cecum, and stool. Bacteroidetes abundance tended to decrease on CCl4 administration and increased following rifaximin treatment in the duodenum and jejunum. S24_7, the most abundant family in Bacteroidetes, demonstrated a significant inverse correlation with Lactobacillaceae (duodenum, r = - 0.61, p < 0.001; jejunum, r = - 0.72, p < 0.001). In the ileum, cecum, and stool, the effect of rifaximin on the microbiota was minimal, with changes within the same phylum. The percentage of bacterial families, such as Lactobacillaceae and S24_7 in the duodenum and small intestine, did not correlate with that in the stool. CONCLUSIONS The abundance of Lactobacillaceae increased in the jejunum of mice with CCl4-induced liver fibrosis, while rifaximin significantly reduced it in the duodenum and jejunum. Thus, rifaximin possibly exerts its effect by altering the duodenal and jejunal microbiota. Furthermore, changes in the duodenal and small intestinal microbiota were not associated with that of stool, suggesting that the analysis of stool microbiota is insufficient to evaluate upper intestinal microbiota.
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Affiliation(s)
- Kazuhiko Ikeuchi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan
| | - Takeya Tsutsumi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan.
- Department of Infection Control and Prevention, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
| | - Aya Ishizaka
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan
| | - Taketoshi Mizutani
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan
| | - Ayako Sedohara
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan
| | - Michiko Koga
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan
| | - Satoru Tamaoki
- Medical Affairs Department, ASKA Pharmaceutical Co., Ltd., 2-5-1, Shibaura, Minato-Ku, Tokyo, 108-8532, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan
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de Wit K, Beuers U, Mukha A, Stigter ECA, Gulersonmez MC, Ramos Pittol JM, Middendorp S, Takkenberg RB, van Mil SWC. Rifaximin stimulates nitrogen detoxification by PXR-independent mechanisms in human small intestinal organoids. Liver Int 2023; 43:649-659. [PMID: 36463417 DOI: 10.1111/liv.15491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 11/30/2022] [Accepted: 12/02/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND AND AIMS Recurrent hepatic encephalopathy (HE) is characterized by hyperammonaemia in combination with neuropsychiatric abnormalities and is treated with lactulose and rifaximin. Rifaximin is a pregnane X receptor (PXR) agonist with low systemic and high intestinal bioavailability. The mechanisms by which it alleviates HE are unclear. We used human small intestinal (hSI) organoids to study whether rifaximin, via PXR activation, affects the epithelial biotransformation machinery, and to gain understanding of its low systemic availability. METHODS We generated PXR knockdown hSI organoids via lentiviral delivery of short hairpin RNAs. Organoids were cultured for 24 h with rifaximin or rifampicin. RNA-sequencing and metabolomics were performed to analyse gene expression and amino acid metabolism. Luminal rifaximin was quantified by photospectrometry. RESULTS Treatment of wild-type hSI organoids with rifaximin resulted in >twofold differential expression of 131 genes compared to DMSO. These effects were largely PXR independent and related to amino acid metabolism. Rifaximin decreased expression of glutaminase-2 and increased expression of asparagine synthetase and solute carrier 7A11, thereby increasing intracellular glutamine and asparagine concentrations, indicating active ammonia detoxification. Rifaximin was apically excreted into the lumen in an ATP binding cassette B1 (ABCB1)-dependent manner. CONCLUSIONS Rifaximin-after uptake into enterocytes-stimulates intracellular nitrogen detoxification by PXR-independent mechanisms. Active apical excretion of rifaximin by ABCB1 into the intestinal lumen explains its low systemic bioavailability. Our study implies that rifaximin, next to modulation of the microbiome, has direct effects on ammonia scavenging in the human small intestinal epithelium.
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Affiliation(s)
- Koos de Wit
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - Anna Mukha
- Center for Molecular Medicine, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Edwin C A Stigter
- Center for Molecular Medicine, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
| | - M Can Gulersonmez
- Center for Molecular Medicine, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Jose M Ramos Pittol
- Center for Molecular Medicine, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Sabine Middendorp
- Division of Paediatric Gastroenterology, Wilhelmina Children's Hospital, UMC Utrecht, Utrecht University, Utrecht, The Netherlands.,Regenerative Medicine Center Utrecht, Utrecht, The Netherlands
| | - R Bart Takkenberg
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
| | - Saskia W C van Mil
- Center for Molecular Medicine, UMC Utrecht, Utrecht University, Utrecht, The Netherlands
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Ouyang Y, Zhao J, Wang S. Multifunctional hydrogels based on chitosan, hyaluronic acid and other biological macromolecules for the treatment of inflammatory bowel disease: A review. Int J Biol Macromol 2023; 227:505-523. [PMID: 36495992 DOI: 10.1016/j.ijbiomac.2022.12.032] [Citation(s) in RCA: 62] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 11/28/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022]
Abstract
Hydrogel is a three-dimensional network polymer material rich in water. It is widely used in the biomedical field because of its unique physical and chemical properties and good biocompatibility. In recent years, the incidence of inflammatory bowel disease (IBD) has gradually increased, and the disadvantages caused by traditional drug treatment of IBD have emerged. Therefore, there is an urgent need for new treatments to alleviate IBD. Hydrogel has become a potential therapeutic platform. However, there is a lack of comprehensive review of functional hydrogels for IBD treatment. This paper first summarizes the pathological changes in IBD sites. Then, the action mechanisms of hydrogels prepared from chitosan, sodium alginate, hyaluronic acid, functionalized polyethylene glycol, cellulose, pectin, and γ-polyglutamic acid on IBD were described from aspects of drug delivery, peptide and protein delivery, biologic therapies, loading probiotics, etc. In addition, the advanced functions of IBD treatment hydrogels were summarized, with emphasis on adhesion, synergistic therapy, pH sensitivity, particle size, and temperature sensitivity. Finally, the future development direction of IBD treatment hydrogels has been prospected.
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Affiliation(s)
- Yongliang Ouyang
- School of Materials and Chemistry, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093,China
| | - Jiulong Zhao
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai 200433, China
| | - Shige Wang
- School of Materials and Chemistry, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093,China.
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Liu Y, Yi Y, Zhong C, Ma Z, Wang H, Dong X, Yu F, Li J, Chen Q, Lin C, Li X. Advanced bioactive nanomaterials for diagnosis and treatment of major chronic diseases. Front Mol Biosci 2023; 10:1121429. [PMID: 36776741 PMCID: PMC9909026 DOI: 10.3389/fmolb.2023.1121429] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 01/17/2023] [Indexed: 01/27/2023] Open
Abstract
With the rapid innovation of nanoscience and technology, nanomaterials have also been deeply applied in the medical and health industry and become one of the innovative methods to treat many diseases. In recent years, bioactive nanomaterials have attracted extensive attention and have made some progress in the treatment of some major chronic diseases, such as nervous system diseases and various malignant tumors. Bioactive nanomaterials depend on their physical and chemical properties (crystal structure, surface charge, surface functional groups, morphology, and size, etc.) and direct produce biological activity and play to the role of the treatment of diseases, compared with the traditional nanometer pharmaceutical preparations, biological active nano materials don't exert effects through drug release, way more directly, also is expected to be more effective for the treatment of diseases. However, further studies are needed in the evaluation of biological effects, fate in vivo, structure-activity relationship and clinical transformation of bionanomaterials. Based on the latest research reports, this paper reviews the application of bioactive nanomaterials in the diagnosis and treatment of major chronic diseases and analyzes the technical challenges and key scientific issues faced by bioactive nanomaterials in the diagnosis and treatment of diseases, to provide suggestions for the future development of this field.
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Affiliation(s)
- Yongfei Liu
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
| | - Yi Yi
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China,*Correspondence: Yi Yi,
| | - Chengqian Zhong
- Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
| | - Zecong Ma
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
| | - Haifeng Wang
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
| | - Xingmo Dong
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
| | - Feng Yu
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
| | - Jing Li
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
| | - Qinqi Chen
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
| | - Chaolu Lin
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
| | - Xiaohong Li
- Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China
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Bitto N, Ghigliazza G, Lavorato S, Caputo C, La Mura V. Improving Management of Portal Hypertension: The Potential Benefit of Non-Etiological Therapies in Cirrhosis. J Clin Med 2023; 12:934. [PMID: 36769582 PMCID: PMC9917703 DOI: 10.3390/jcm12030934] [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: 12/30/2022] [Revised: 01/17/2023] [Accepted: 01/20/2023] [Indexed: 01/27/2023] Open
Abstract
Portal hypertension is the consequence of cirrhosis and results from increased sinusoidal vascular resistance and hepatic blood inflow. Etiological therapies represent the first intervention to prevent a significant increase in portal pressure due to chronic liver damage. However, other superimposed pathophysiological drivers may worsen liver disease, including inflammation, bacterial translocation, endothelial dysfunction, and hyperactivation of hemostasis. These mechanisms can be targeted by a specific class of drugs already used in clinical practice. Albumin, rifaximin, statins, aspirin, and anticoagulants have been tested in cirrhosis and were a topic of discussion in the last Baveno consensus as non-etiological therapies. Based on the pathogenesis of portal hypertension in cirrhosis, our review summarizes the main mechanisms targeted by these drugs as well as the clinical evidence that considers them a valid complementary option to manage patients with cirrhosis and portal hypertension.
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Affiliation(s)
- Niccolò Bitto
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy
| | - Gabriele Ghigliazza
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Sub-Intensive Care Medicine, 20122 Milan, Italy
| | - Stanislao Lavorato
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy
| | - Camilla Caputo
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy
| | - Vincenzo La Mura
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
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Luo M, Xin RJ, Hu FR, Yao L, Hu SJ, Bai FH. Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis. World J Gastroenterol 2023; 29:144-156. [PMID: 36683714 PMCID: PMC9850958 DOI: 10.3748/wjg.v29.i1.144] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/23/2022] [Accepted: 12/14/2022] [Indexed: 01/04/2023] Open
Abstract
Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.
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Affiliation(s)
- Ming Luo
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Rui-Juan Xin
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Fang-Rui Hu
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Li Yao
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Sheng-Juan Hu
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
| | - Fei-Hu Bai
- Department of Gastroenterology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, Ningxia Hui Autonomous Region, China
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Highly Polymorphic Materials and Dissolution Behaviour: The Peculiar Case of Rifaximin. Pharmaceutics 2022; 15:pharmaceutics15010053. [PMID: 36678682 PMCID: PMC9865978 DOI: 10.3390/pharmaceutics15010053] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/18/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open
Abstract
Rifaximin is a locally acting antibiotic practically insoluble in water. It presents several crystal phases characterized by different degrees of hydration. The aim of this work is to investigate the dissolution behaviour of rifaximin α, β, and amorphous forms in relation to their relative thermodynamic stability to contribute to clarifying possible solvent- or humidity-mediated conversion patterns. Kinetic and intrinsic solubility were investigated along with particle size distribution, specific surface area, and external morphology. The solution and moisture mediated conversion from metastable α and amorphous forms to stable β form were elucidated by coupling intrinsic dissolution test with chemometric analysis as well as by dynamic vapour sorption measurements. The dissolution behaviour of the α form stems mainly from the transition to β form that occurs upon exposition to relative humidity higher than 40%. The α form converted more rapidly than the amorphous form due to the smaller supersaturation ratio. It can be concluded that, due to its marked tendency to transform into β form, the dissolution test for the α form, even if conducted according to compendial procedures, needs to be accompanied by a panel of further tests that allow to uniquely identify the solid phase under investigation.
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Mechanical bowel preparation with or without oral antibiotics for rectal resection for cancer (REPCA trial): a study protocol for a multicenter randomized controlled trial. Tech Coloproctol 2022; 27:389-396. [PMID: 36151343 DOI: 10.1007/s10151-022-02706-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 09/11/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND There is still a lack of randomized trials assessing the clinical value of mechanical bowel preparation (MBP) and oral antibiotics (OA) before rectal surgery. Existing studies are inconsistent regarding OA. The aim of this study is to examine the role of MBP with or without OA (using Alfa Normix®) on postoperative complications in patients undergoing rectal resection for cancer. METHODS We are conducting a prospective multicenter randomized controlled trial comparing MBP (Moviprep®) with OA (Alfa Normix®) versus MBP alone in patients undergoing elective rectal resection for cancer. Patients with rectal or rectosigmoid cancer are randomized in a 1:1 allocation ratio. The primary endpoint is incisional surgical site infection (SSI) assessed within 30 days after surgery. Secondary endpoints are anastomotic leakage (AL), organ/space SSI, other postoperative complications, intraoperative complications, operation time, bowel preparation quality, bowel preparation adherence. Intention-to-treat and per protocol analyses will be performed. CONCLUSIONS The results of the REPCA trial will demonstrate whether MBP + OA is superior to MBP alone in rectal cancer surgery. This trial might influence current preoperative practice and improve postoperative outcomes.
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Wang Y, Tang J, Zhou S, Liang TT, Wang FF, Ning H. Effectiveness and Safety of Rifaximin-Containing Regimens for Helicobacter pylori Eradication: Systematic Review - Are They Potential Eradication Regimens? Infect Drug Resist 2022; 15:3733-3749. [PMID: 35859911 PMCID: PMC9289174 DOI: 10.2147/idr.s371131] [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: 04/17/2022] [Accepted: 07/04/2022] [Indexed: 11/30/2022] Open
Abstract
Background Rifaximin, a rifamycin antibiotic, is widely used to treat infectious diarrhea but not commonly used in H. pylori eradication. With its potential advantages of the agent, some studies were conducted on this topic. The aim of this study is to assess effectiveness and safety of rifaximin-containing regimens and to evaluate whether they are alternative choices for H. pylori eradication. Methods Scientific databases including PubMed, EMbase and Cochrane Library were used to identify clinical trials on rifaximin-containing regimens published from January 2000 to October 2021. Review Manager 5.4 and STATA12 were adopted for the systematic review. Results In this study, totally 1025 patients were included from 3 randomized controlled and 9 single-arm studies. It showed that the differences in effectiveness and safety between rifaximin-containing and first-line regimens were not statistically significant in randomized controlled trials. However, the results of the single-arm trials indicated that the eradication and adverse drug reaction rate varied suggesting data instability (r=38.1%-85.4%, rADR 0.00–67.5% by ITT analysis). Among them, the eradication rate of pediatric patients (r=85.4% by ITT analysis) was higher than that of adult patients (r=38.1–74.5% by ITT analysis). Meanwhile, in all adult subgroups (triple or quadruple, with or without amoxicillin, different duration and rifaximin dose), the results did not show sufficient effectiveness as all the eradication rates did not meet the minimum ideal or ideal target. Conclusion Taken together, rifaximin-containing regimens should not be recommended for H. pylori eradication as they cannot achieve the eradication rate desired.
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Affiliation(s)
- Yu Wang
- Department of Pharmacy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, People's Republic of China
| | - Jiong Tang
- Department of Pharmacy, Sichuan Second Hospital of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Su Zhou
- Department of Pharmacy, Sichuan GEM Flower Hospital, Chengdu, People's Republic of China
| | - Tian-Tian Liang
- Department of Pharmacy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, People's Republic of China
| | - Fang-Fang Wang
- Department of Pharmacy, Emeishan People's Hospital, Emeishan, People's Republic of China
| | - Hong Ning
- Department of Pharmacy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, People's Republic of China
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Liu Y, Chen M. Clostridioides difficile Infection in Liver Cirrhosis: A Concise Review. Can J Gastroenterol Hepatol 2022; 2022:4209442. [PMID: 35711246 PMCID: PMC9197604 DOI: 10.1155/2022/4209442] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 04/04/2022] [Accepted: 05/24/2022] [Indexed: 12/16/2022] Open
Abstract
Clostridium difficile is a Gram-positive bacillus with fecal-oral transmission and is currently one of the most common nosocomial infections worldwide, which was renamed Clostridioides difficile in 2016. Clostridioides difficile infection (CDI) is a prevalent infection in cirrhosis and negatively affects prognosis. This study aimed to provide a concise review with clinical practice implications. The prevalence of CDI in cirrhotic patients increases, while the associated mortality decreases. Multiple groups of risk factors increase the likelihood of CDI in patients with cirrhosis, such as antibiotic use, the severity of cirrhosis, some comorbidities, and demographic aspects. Treatment in the general population is currently described in the latest guidelines. In patients with cirrhosis, rifaximin and lactulose have been shown to reduce CDI risk due to their modulatory effects on the intestinal flora, although conflicting results exist. Fecal microbiota transplantation (FMT) as a treatment for the second or subsequent CDI recurrences has demonstrated a good safety and efficacy in cirrhosis and CDI. Future validation in more prospective studies is needed. Screening of asymptomatic patients appears to be discouraged for the prevention currently, with strict hand hygiene and cleaning of the ward and medical equipment surfaces being the cornerstone of minimizing transmission.
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Affiliation(s)
- Yuanbin Liu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhidong Road, Wuhan 430000, Hubei, China
| | - Mingkai Chen
- Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhidong Road, Wuhan 430000, Hubei, China
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Mitochondrial Side Effects of Surgical Prophylactic Antibiotics Ceftriaxone and Rifaximin Lead to Bowel Mucosal Damage. Int J Mol Sci 2022; 23:ijms23095064. [PMID: 35563455 PMCID: PMC9103148 DOI: 10.3390/ijms23095064] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/28/2022] [Accepted: 04/30/2022] [Indexed: 02/04/2023] Open
Abstract
Despite their clinical effectiveness, a growing body of evidence has shown that many classes of antibiotics lead to mitochondrial dysfunction. Ceftriaxone and Rifaximin are first choice perioperative antibiotics in gastrointestinal surgery targeting fundamental processes of intestinal bacteria; however, may also have negative consequences for the host cells. In this study, we investigated their direct effect on mitochondrial functions in vitro, together with their impact on ileum, colon and liver tissue. Additionally, their impact on the gastrointestinal microbiome was studied in vivo, in a rat model. Rifaximin significantly impaired the oxidative phosphorylation capacity (OxPhos) and leak respiration in the ileal mucosa, in line with increased oxidative tissue damage and histological changes following treatment. Ceftriaxone prophylaxis led to similar changes in the colon mucosa. The composition and diversity of bacterial communities differed extensively in response to antibiotic pre-treatment. However, the relative abundances of the toxin producing species were not increased. We have confirmed the harmful effects of prophylactic doses of Rifaximin and Ceftriaxone on the intestinal mucosa and that these effects were related to the mitochondrial dysfunction. These experiments raise awareness of mitochondrial side effects of these antibiotics that may be of clinical importance when evaluating their adverse effects on bowel mucosa.
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Luo W, Guo S, Zhou Y, Zhao J, Wang M, Sang L, Chang B, Wang B. Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy. Front Microbiol 2022; 13:873160. [PMID: 35572649 PMCID: PMC9092458 DOI: 10.3389/fmicb.2022.873160] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/05/2022] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota is gaining increasing attention, and the concept of the "gut-liver axis" is gradually being recognized. Leaky gut resulting from injury and/or inflammation can cause the translocation of flora to the liver. Microbiota-associated metabolites and components mediate the activation of a series of signalling pathways, thereby playing an important role in the development of hepatocellular carcinoma (HCC). For this reason, targeting the gut microbiota in the diagnosis, prevention, and treatment of HCC holds great promise. In this review, we summarize the gut microbiota and the mechanisms by which it mediates HCC development, and the characteristic alterations in the gut microbiota during HCC pathogenesis. Furthermore, we propose several strategies to target the gut microbiota for the prevention and treatment of HCC, including antibiotics, probiotics, faecal microbiota transplantation, and immunotherapy.
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Affiliation(s)
- Wenyu Luo
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
- The Second Clinical College, China Medical University, Shenyang, China
| | - Shiqi Guo
- The Second Clinical College, China Medical University, Shenyang, China
| | - Yang Zhou
- The Second Clinical College, China Medical University, Shenyang, China
| | - Jingwen Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mengyao Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lixuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bing Chang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Bingyuan Wang
- Department of Geriatric Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China
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An animal model of limitation of gut colonization by carbapenemase-producing Klebsiella pneumoniae using rifaximin. Sci Rep 2022; 12:3789. [PMID: 35260705 PMCID: PMC8904601 DOI: 10.1038/s41598-022-07827-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 02/14/2022] [Indexed: 11/17/2022] Open
Abstract
Current knowledge suggests that infection by carbapenem-resistant enterobacteria is preceded by gut colonization. It is hypothesized that colonization is eradicated by non-absorbable antibiotics like rifaximin. We investigated the effect of rifaximin against carbapenem-resistant Klebsiella pneumoniae (CRKP) in vitro and in a mouse model. We studied the in vitro efficacy of rifaximin against 257 CRKP clinical isolates, 188 KPC producers and 69 OXA-48 producers, by minimum inhibitory concentration and time-kill assays. We then developed a model of gut colonization by feeding 30 C57Bl6 mice with 108 cfu of one KPC-KP isolate for 7 days; mice were pre-treated orally with saline, omeprazole or ampicillin. Then, another 60 mice with established KPC-2 gut colonization received orally for 7 consecutive days rifaximin 180 mg/kg dissolved in ethanol and 4% bile or vehicle. On days 0, 3 and 7 stool samples were collected; mice were sacrificed for determination of tissue outgrowth. At a concentration of 1000 μg/ml rifaximin inhibited 84.8% of CRKP isolates. Α 3 × log10 decrease of the starting inoculum was achieved by 100, 250 and 500 μg/ml of rifaximin after 24 h against 25, 55 and 55% of isolates. Pre-treatment with ampicillin was necessary for gut colonization by KPC-KP. Treatment with rifaximin succeeded in reducing KPC-KP load in stool and in the intestine. Rifaximin inhibits at clinically meaningful gut concentrations the majority of CRKP isolates and is efficient against gut colonization by KPC-KP.
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Dogan H, Ocal H, Safak T, Kilinc MA, Risvanli A. Dose related inhibitor effect of enrofloxacin on in vitro feline spontaneous myometrial contractility. Anim Reprod Sci 2022; 239:106972. [DOI: 10.1016/j.anireprosci.2022.106972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 03/16/2022] [Accepted: 03/20/2022] [Indexed: 11/29/2022]
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Lalan M, Shah P, Kadam R, Patel H. Amalgam of ternary solid dispersion and P-gp efflux inhibition in development of colon-targeted tablets of rifaximin. JOURNAL OF REPORTS IN PHARMACEUTICAL SCIENCES 2022. [DOI: 10.4103/jrptps.jrptps_21_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Ko SJ, Cho M, Bae J, Park JH, Bu Y, Lee BJ, Park JW, Kim J, Yoo H. Protective effect of the traditional Korean herbal prescription, Bojangunbi-tang, on non-steroidal anti-inflammatory drug-induced small bowel injury. Pharmacogn Mag 2022. [DOI: 10.4103/pm.pm_333_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Scarpignato C, Stollman N. Non-Absorbable Antibiotics. COLONIC DIVERTICULAR DISEASE 2022:209-234. [DOI: 10.1007/978-3-030-93761-4_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Amaldoss MJN, Najar IA, Kumar J, Sharma A. Therapeutic efficacy of rifaximin loaded tamarind gum polysaccharide nanoparticles in TNBS induced IBD model Wistar rats. Rep Pract Oncol Radiother 2021; 26:712-729. [PMID: 34760306 DOI: 10.5603/rpor.a2021.0100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 05/12/2021] [Indexed: 12/25/2022] Open
Abstract
Background Rifaximin is a non-systemic antibiotic used in the treatment of inflammatory bowel disease (IBD). Antibiotics are demonstrating a significant role in the treatment of IBD by altering the dysbiotic colonic microbiota and decreases the immunogenic and inflammatory response in the patient population. Mucoadhesive colon targeted nanoparticles provide the site-specific delivery and extended stay in the colon. Since the bacteria occupy the lumen, spread over the surface of epithelial cells, and adhere to the mucosa, delivering the rifaximin as a nanoparticles with the mucoadhesive polymer enhances the therapeutic efficacy in IBD. The objective was to fabricate and characterize the rifaximin loaded tamarind gum nanoparticles and study the therapeutic efficacy in the TNBS-induced IBD model rats. Materials and methods The experimentation includes fabrication and characterization of drug excipient compatibility by FTIR. The fabricated nanoparticles were characterized for the hydrodynamic size and zeta potential by photon correlation spectroscopy and also analyzed by TEM. Selected best formulation was subjected to the therapeutic efficacy study in TNBS-induced IBD rats, and the macroscopic, microscopic and biochemical parameters were reported. Results The study demonstrated that the formulation TGN1 is best formulation in terms of nanoparticle characterization and hydrodynamic size which showed the hydrodynamic size of 171.4 nm and the zeta potential of -26.44 mV and other parameters such as TEM and drug release studies were also reported. Conclusions The therapeutic efficacy study revealed that TGN1 is efficiently reduced the IBD inflammatory conditions as compared to the TNBS control group and reference drug mesalamine group.
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Affiliation(s)
- Maria John Newton Amaldoss
- Australian Centre for Nanomedicine, University of New South Wales, Sydney, NSW 2052, Australia.,Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.,Swift School of Pharmacy Rajpura, Punjab, India
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Han X, Luo Z, Wang W, Zheng P, Li T, Mei Z, Wang J. Efficacy and Safety of Rifaximin Versus Placebo or Other Active Drugs in Critical ill Patients With Hepatic Encephalopathy. Front Pharmacol 2021; 12:696065. [PMID: 34690751 PMCID: PMC8533823 DOI: 10.3389/fphar.2021.696065] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 09/21/2021] [Indexed: 12/11/2022] Open
Abstract
Objective: Rifaximin has been approved for use as a first-line therapy for secondary prophylaxis of hepatic encephalopathy (HE). This article is to update existing evidence on efficacy and safety of rifaximin treatment and prevention for HE. Methods: We systematically searched multiple databases until January 31 2021. The studies compared rifaximin vs. placebo or other active drugs (i.e., nonabsorbable disaccharides, other antibiotics, L-ornithine-L-aspartate (LOLA), and probiotics) for patients with overt HE (OHE), minimal HE (MHE), and recurrent HE. Results: Twenty-eight randomized controlled trials with a total of 2979 patients were included. Compared with the controls, rifaximin significantly reduced HE grade (OHE: RR = 1.11, 95% CI = 1.02-1.21), improved the cognitive impairments (MHE: RR = 1.82, 95% CI = 1.12-2.93) and prevented the risk of HE recurrent episodes (RR = 1.33, 95% CI = 1.18-1.49). No statistical difference was observed in mortality between rifaximin and their controls (RR = 0.82, 95% CI = 0.54-1.24). The incidence of total adverse events in rifaximin-treated groups was significantly lower than that in the controls during the treatment period (RR = 0.73, 95% CI = 0.54-0.98). In addition, rifaximin treatment was better than other active drugs in improving psychometric indicators (mental state, flapping tremor and portosystemic encephalopathy (PSE) index) and reducing the risk of rehospitalization in HE patients. Conclusion: Rifaximin therapy is effective and well-tolerated in different types of HE, which might be recommended as an alternative to conventional oral drugs in clinical settings.
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Affiliation(s)
- Xianghui Han
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhanyang Luo
- Institute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wenyi Wang
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Peiyong Zheng
- Institute of Digestive Diseases, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tian Li
- School of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Zubing Mei
- Department of Anorectal Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Anorectal Disease Institute of Shuguang Hospital, Shanghai, China
| | - Jianyi Wang
- Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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42
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Zaccherini G, Tufoni M, Bernardi M, Caraceni P. Prevention of Cirrhosis Complications: Looking for Potential Disease Modifying Agents. J Clin Med 2021; 10:4590. [PMID: 34640608 PMCID: PMC8509683 DOI: 10.3390/jcm10194590] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/29/2021] [Accepted: 10/04/2021] [Indexed: 02/07/2023] Open
Abstract
The current therapeutic strategies for the management of patients with cirrhosis rely on the prevention or treatment of specific complications. The removal of the causative agents (i.e., viruses or alcohol) prevents decompensation in the vast majority of patients with compensated cirrhosis. In contrast, even when etiological treatment has been effective, a significant proportion of patients with decompensated cirrhosis remains at risk of further disease progression. Therefore, therapies targeting specific key points in the complex pathophysiological cascade of decompensated cirrhosis could represent a new approach for the management of these severely ill patients. Some of the interventions currently employed for treating or preventing specific complications of cirrhosis or used in other diseases (i.e., poorly absorbable oral antibiotics, statins, albumin) have been proposed as potential disease-modifying agents in cirrhosis (DMAC) since clinical studies have shown their capacity of improving survival. Additional multicenter, large randomized clinical trials are awaited to confirm these promising results. Finally, new drugs able to antagonize key pathophysiological mechanisms are under pre-clinical development or at the initial stages of clinical assessment.
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Affiliation(s)
- Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.Z.); (M.B.)
| | - Manuel Tufoni
- IRCCS AOU di Bologna—Policlinico di S. Orsola, 40138 Bologna, Italy;
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.Z.); (M.B.)
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.Z.); (M.B.)
- IRCCS AOU di Bologna—Policlinico di S. Orsola, 40138 Bologna, Italy;
- Center for Biomedical Applied Research, University of Bologna, 40138 Bologna, Italy
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43
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Sohal A, Green V, Sandhu S, Roytman M. Identifying areas of improvement in nursing knowledge regarding hepatic encephalopathy management. J Community Hosp Intern Med Perspect 2021; 11:722-726. [PMID: 34567473 PMCID: PMC8462881 DOI: 10.1080/20009666.2021.1954784] [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] [Indexed: 10/25/2022] Open
Abstract
Hepatic encephalopathy (HE) is a reversible brain dysfunction caused by liver insufficiency and portosystemic shunting. Hepatic encephalopathy is a common complication of advanced liver disease and is on a rise with the increasing incidence of non-alcoholic steatohepatitis (NASH). Since partnership with nursing staff is a critical part of successful management of these complex patients, we conducted a survey assessing their knowledge regarding HE.169 nurses participated in the survey. We found that more than 30% of the nurses did not know that ammonia is one of the toxins responsible for causing hepatic encephalopathy. We also found that 20% of the nurses had difficulty answering questions regarding titration of lactulose to bowel movements. Dietary education is a significant area for improvement as 80% of the nurses wanted to restrict fat and carbohydrate intake in these patients. With this simple survey, we identified important knowledge gaps among experienced nurses at our institution. We believe that by improving knowledge through focused lectures, we can improve patient care and reduce the length of hospitalizations in patients with HE.
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Affiliation(s)
- Aalam Sohal
- Department of Internal Medicine , UCSF Fresno, Fresno, USA
| | - Victoria Green
- Department of Internal Medicine , UCSF Fresno, Fresno, USA
| | - Sunny Sandhu
- Department of Internal Medicine , UCSF Fresno, Fresno, USA
| | - Marina Roytman
- Department of Gastroenterology and Hepatology, UCSF Fresno, Fresno, USA
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44
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Caraceni P, Vargas V, Solà E, Alessandria C, de Wit K, Trebicka J, Angeli P, Mookerjee RP, Durand F, Pose E, Krag A, Bajaj JS, Beuers U, Ginès P, Napoleone L, Carol M, Avitabile E, Thu AM, Cervera M, Pérez M, Belén Rubio‐Garcia A, Ardiaca A, Vives A, Pich J, Fabrellas N, Zaccherini G, Chiappa MT, Jiménez C, Palacio E, Campion D, Lanzillotti T, Piano S, Nicolao G, Uschner F, Graf_Dirmeier S, Francoz C, Roux O, Esnault V, Helder J, Aban M, Kazankov K, Korenjak M, Kamath P, Abraldes JG, Watson H. The Use of Rifaximin in Patients With Cirrhosis. Hepatology 2021; 74:1660-1673. [PMID: 33421158 PMCID: PMC8518409 DOI: 10.1002/hep.31708] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 11/10/2020] [Accepted: 12/02/2020] [Indexed: 12/12/2022]
Abstract
Rifaximin is an oral nonsystemic antibiotic with minimal gastrointestinal absorption and broad-spectrum antibacterial activity covering both gram-positive and gram-negative organisms. Rifaximin is currently used worldwide in patients with cirrhosis for preventing recurrent HE because its efficacy and safety have been proven by large randomized clinical trials. In the last decade, experimental and clinical evidence suggest that rifaximin could have other beneficial effects on the course of cirrhosis by modulating the gut microbiome and affecting the gut-liver axis, which in turn can interfere with major events of the pathophysiological cascade underlying decompensated cirrhosis, such as systemic inflammatory syndrome, portal hypertension, and bacterial infections. However, the use of rifaximin for prevention or treatment of other complications, including spontaneous bacterial peritonitis or other bacterial infections, is not accepted because evidence by clinical trials is still very weak. The present review deals in the first part with the potential impact of rifaximin on pathogenic mechanisms in liver diseases, whereas in the second part, its clinical effects are critically discussed. It clearly emerges that, because of its potential activity on multiple pathogenic events, the efficacy of rifaximin in the prevention or management of complications other than HE deserves to be investigated extensively. The results of double-blinded, adequately powered randomized clinical trials assessing the effect of rifaximin, alone or in combination with other drugs, on hard clinical endpoints, such as decompensation of cirrhosis, acute-on-chronic liver failure, and mortality, are therefore eagerly awaited.
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Affiliation(s)
- Paolo Caraceni
- University of BolognaUniversity Hospital S. Orsola‐Malpighi di BolognaBolognaItaly
| | - Victor Vargas
- Hospital Vall d’HebronUniversitat Autònoma de BarcelonaCIEREHDBarcelonaCataloniaSpain
| | - Elsa Solà
- Hospital Clinic of BarcelonaUniversity of BarcelonaIDIBAPSCIBEReHDBarcelonaCataloniaSpain
| | - Carlo Alessandria
- Division of Gastroenterology and HepatologyCittà della Salute e della Scienza HospitalUniversity of TorinoTurinItaly
| | - Koos de Wit
- Amsterdam University Medical CentersAmsterdamthe Netherlands
| | - Jonel Trebicka
- Goethe‐University ‐ Frankfurt am MainFrankfurt am MainGermany,EF‐CLIFBarcelonaCataloniaSpain
| | | | | | | | - Elisa Pose
- Hospital Clinic of BarcelonaUniversity of BarcelonaIDIBAPSCIBEReHDBarcelonaCataloniaSpain
| | - Aleksander Krag
- Department of Gastroenterology and HepatologyOdense University HospitalOdenseDenmark,Institute of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
| | | | - Ulrich Beuers
- Amsterdam University Medical CentersAmsterdamthe Netherlands
| | - Pere Ginès
- Hospital Clinic of BarcelonaUniversity of BarcelonaIDIBAPSCIBEReHDBarcelonaCataloniaSpain
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45
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Chang C, Huang CH, Tseng HJ, Yang FC, Chien RN. Real-World Experience of the One-Year Efficacy of Rifaximin Add-On to Lactulose Is Superior to Lactulose Alone in Patients with Cirrhosis Complicated with Recurrent Hepatic Encephalopathy in Taiwan. J Pers Med 2021; 11:478. [PMID: 34071787 PMCID: PMC8226737 DOI: 10.3390/jpm11060478] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 05/21/2021] [Accepted: 05/21/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE), a neuropsychiatric complication of decompensated cirrhosis, is associated with high mortality and high risk of recurrence. Rifaximin add-on to lactulose for 3 to 6 months is recommended for the prevention of recurrent episodes of HE after the second episode. However, whether the combination for more than 6 months is superior to lactulose alone in the maintenance of HE remission is less evident. Therefore, the aim of this study is to evaluate the one-year efficacy of rifaximin add-on to lactulose for the maintenance of HE remission in Taiwan. METHODS We conducted a real-world single-center retrospective cohort study to compare the long-term efficacy of rifaximin add-on to lactulose (group R + L) versus lactulose alone (group L, control group). Furthermore, the treatment efficacy before and after rifaximin add-on to lactulose was also analyzed. The primary endpoint of our study was time to first HE recurrence (Conn score ≥ 2). All patients were followed up every three months until death, and censored at one year if still alive. RESULTS AND CONCLUSIONS 12 patients were enrolled in group R + L. Another 31 patients were stratified into group L. Sex, comorbidity, ammonia level, and ascites grade were matched while age, HE grade, and model for end-stage liver disease (MELD) score were adjusted in the multivariable logistic regression model. Compared with group L, significant improvement in the maintenance of HE remission and decreased episodes and days of HE-related hospitalizations were demonstrated in group R + L. The serum ammonia levels were significantly lower at the 3rd and 6th month in group 1. Concerning changes before and after rifaximin add-on in group R + L, mini-mental status examination (MMSE), episodes of hospitalization, and variceal bleeding also improved at 6 and 12 months. Days of hospitalization, serum ammonia levels also improved at 6th month. Except for concern over price, no patients discontinued rifaximin due to adverse events or complications. The above results provide evidence for the one-year use of rifaximin add-on to lactulose in reducing HE recurrence and HE-related hospitalization for patients with decompensated cirrhosis.
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Affiliation(s)
- Ching Chang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; (C.C.); (C.-H.H.); (F.-C.Y.)
| | - Chien-Hao Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; (C.C.); (C.-H.H.); (F.-C.Y.)
- College of Medicine, Chang-Gung University, Taoyuan 33305, Taiwan
| | - Hsiao-Jung Tseng
- Biostatistics Unit, Clinical Trial Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan;
| | - Fang-Chen Yang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; (C.C.); (C.-H.H.); (F.-C.Y.)
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; (C.C.); (C.-H.H.); (F.-C.Y.)
- College of Medicine, Chang-Gung University, Taoyuan 33305, Taiwan
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46
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McHale C, Keating E, O'Donovan H, Slattery E. D-lactic acidosis presenting as metabolic encephalopathy in a patient with short bowel syndrome. BMJ Case Rep 2021; 14:14/5/e241102. [PMID: 33986009 PMCID: PMC8126269 DOI: 10.1136/bcr-2020-241102] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
We present a case of D-lactic acidosis presenting as a metabolic encephalopathy secondary to small intestinal bacterial overgrowth. This patient had a known history of short bowel syndrome. Of note, this case required the alteration of treatment to promote a sustained clinical and biochemical improvement. We discuss the pathophysiological mechanisms thought to be involved. We also review the current therapies as well as potential future strategies. This case highlights the importance of the prompt clinical recognition of signs and symptoms as well as the rapid initiation of management strategies to ameliorate this condition.
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Affiliation(s)
- Ciarán McHale
- Department of Gastroenterology, Galway University Hospital, Galway, Ireland
| | - Eoin Keating
- Department of Gastroenterology, Galway University Hospital, Galway, Ireland
| | - Helen O'Donovan
- Department of Gastroenterology, Galway University Hospital, Galway, Ireland
| | - Eoin Slattery
- Department of Gastroenterology, Galway University Hospital, Galway, Ireland
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47
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Theis KR, Florova V, Romero R, Borisov AB, Winters AD, Galaz J, Gomez-Lopez N. Sneathia: an emerging pathogen in female reproductive disease and adverse perinatal outcomes. Crit Rev Microbiol 2021; 47:517-542. [PMID: 33823747 DOI: 10.1080/1040841x.2021.1905606] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Sneathia is an emerging pathogen implicated in adverse reproductive and perinatal outcomes. Although scarce, recent data suggest that vaginally residing Sneathia becomes pathogenic following its ascension into the upper urogenital tract, amniotic fluid, placenta, and foetal membranes. The role of Sneathia in women's health and disease is generally underappreciated because the cultivation of these bacteria is limited by their complex nutritional requirements, slow growth patterns, and anaerobic nature. For this reason, molecular methods are typically required for the detection and differential diagnosis of Sneathia infections. Here, we review the laboratory methods used for the diagnosis of Sneathia infections, the molecular mechanisms underlying its virulence, and its sensitivity to antibiotics. We further review the evidence of Sneathia's contributions to the pathogenesis of bacterial vaginosis, chorioamnionitis, preterm prelabour rupture of membranes, spontaneous preterm labour, stillbirth, maternal and neonatal sepsis, HIV infection, and cervical cancer. Collectively, growing evidence indicates that Sneathia represents an important yet underappreciated pathogen affecting the development and progression of several adverse clinical conditions diagnosed in pregnant women and their neonates, as well as in non-pregnant women.
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Affiliation(s)
- Kevin R Theis
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, USA.,Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Violetta Florova
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, USA.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Roberto Romero
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, USA.,Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.,Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.,Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.,Detroit Medical Center, Detroit, MI, USA.,Department of Obstetrics and Gynecology, Florida International University, Miami, FL, USA
| | - Andrei B Borisov
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, USA.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Andrew D Winters
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, USA.,Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Jose Galaz
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, USA.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Nardhy Gomez-Lopez
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, USA.,Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, USA.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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48
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Laube R, Paramsothy S, Leong RW. Use of medications during pregnancy and breastfeeding for Crohn's disease and ulcerative colitis. Expert Opin Drug Saf 2021; 20:275-292. [PMID: 33412078 DOI: 10.1080/14740338.2021.1873948] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Introduction: The peak age of diagnosis of inflammatory bowel disease (IBD) occurs during childbearing years, therefore management of IBD during pregnancy is a frequent occurrence. Maintenance of disease remission is crucial to optimize pregnancy outcomes, and potential maternal or fetal toxicity from medications must be balanced against the risks of untreated IBD.Areas covered: This review summarizes the literature on safety and use of medications for IBD during pregnancy and lactation.Expert opinion: 5-aminosalicylates, corticosteroids and thiopurines are safe for use during pregnancy, while methotrexate and tofacitinib should only be used with extreme caution. Anti-TNF agents (except certolizumab), vedolizumab, ustekinumab and tofacitinib readily traverse the placenta via active transport, therefore theoretically may affect fetal development. Certolizumab only undergoes passive transfer across the placenta, thus has markedly lower cord blood levels making it likely the safest biologic agent for infants. There is reasonable evidence to support the safety of anti-TNF monotherapy and combination therapy during pregnancy and lactation. Vedolizumab and ustekinumab are also thought to be safe in pregnancy and lactation, while tofacitinib is generally avoided due to teratogenic effects in animal studies.
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Affiliation(s)
- Robyn Laube
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.,Department of Gastroenterology, Macquarie University Hospital, Sydney, Australia
| | - Sudarshan Paramsothy
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.,Department of Gastroenterology, Macquarie University Hospital, Sydney, Australia.,Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
| | - Rupert W Leong
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.,Department of Gastroenterology, Macquarie University Hospital, Sydney, Australia.,Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
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49
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Kessoku T, Kobayashi T, Imajo K, Tanaka K, Yamamoto A, Takahashi K, Kasai Y, Ozaki A, Iwaki M, Nogami A, Honda Y, Ogawa Y, Kato S, Higurashi T, Hosono K, Yoneda M, Okamoto T, Usuda H, Wada K, Kobayashi N, Saito S, Nakajima A. Endotoxins and Non-Alcoholic Fatty Liver Disease. Front Endocrinol (Lausanne) 2021; 12:770986. [PMID: 34777261 PMCID: PMC8586459 DOI: 10.3389/fendo.2021.770986] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 10/18/2021] [Indexed: 01/18/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It occurs with a prevalence of up to 25%, of which 10-20% cases progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The histopathology of NASH is characterized by neutrophilic infiltration, and endotoxins from gram-negative rods have been postulated as a contributing factor. Elevations in endotoxin levels in the blood can be classified as intestinal and hepatic factors. In recent years, leaky gut syndrome, which is characterized by impaired intestinal barrier function, has become a significant issue. A leaky gut may prompt intestinal bacteria dysbiosis and increase the amount of endotoxin that enters the liver from the portal vein. These contribute to persistent chronic inflammation and progressive liver damage. In addition, hepatic factors suggest that liver damage can be induced by low-dose endotoxins, which does not occur in healthy individuals. In particular, increased expression of CD14, an endotoxin co-receptor in the liver, may result in leptin-induced endotoxin hyper-responsiveness in obese individuals. Thus, elevated blood endotoxin levels contribute to the progression of NASH. The current therapeutic targets for NASH treat steatosis and liver inflammation and fibrosis. While many clinical trials are underway, no studies have been performed on therapeutic agents that target the intestinal barrier. Recently, a randomized placebo-controlled trial examined the role of the intestinal barrier in patients with NAFLD. To our knowledge, this study was the first of its kind and study suggested that the intestinal barrier may be a novel target in the future treatment of NAFLD.
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Affiliation(s)
- Takaomi Kessoku
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Department of Palliative Medicine, Yokohama City University Hospital, Yokohama, Japan
- *Correspondence: Takaomi Kessoku,
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kento Imajo
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kosuke Tanaka
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Department of Palliative Medicine, Yokohama City University Hospital, Yokohama, Japan
| | - Atsushi Yamamoto
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kota Takahashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yuki Kasai
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Anna Ozaki
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Michihiro Iwaki
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Department of Palliative Medicine, Yokohama City University Hospital, Yokohama, Japan
| | - Asako Nogami
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yasushi Honda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yuji Ogawa
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Shingo Kato
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takuma Higurashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kunihiro Hosono
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takayuki Okamoto
- Department of Pharmacology, Shimane University Faculty of Medicine, Izumo, Japan
| | - Haruki Usuda
- Department of Pharmacology, Shimane University Faculty of Medicine, Izumo, Japan
| | - Koichiro Wada
- Department of Pharmacology, Shimane University Faculty of Medicine, Izumo, Japan
| | - Noritoshi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Department of Oncology, Yokohama City University Hospital, Yokohama, Japan
| | - Satoru Saito
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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50
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Qi X, Yang M, Stenberg J, Dey R, Fogwe L, Alam MS, Kimchi ET, Staveley-O'Carroll KF, Li G. Gut microbiota mediated molecular events and therapy in liver diseases. World J Gastroenterol 2020; 26:7603-7618. [PMID: 33505139 PMCID: PMC7789060 DOI: 10.3748/wjg.v26.i48.7603] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/24/2020] [Accepted: 12/06/2020] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota is a community of microorganisms that reside in the gastrointestinal tract. An increasing number of studies has demonstrated that the gut-liver axis plays a critical role in liver homeostasis. Dysbiosis of gut microbiota can cause liver diseases, including nonalcoholic fatty liver disease and alcoholic liver disease. Preclinical and clinical investigations have substantiated that the metabolites and other molecules derived from gut microbiota and diet interaction function as mediators to cause liver fibrosis, cirrhosis, and final cancer. This effect has been demonstrated to be associated with dysregulation of intrahepatic immunity and liver metabolism. Targeting these findings have led to the development of novel preventive and therapeutic strategies. Here, we review the cellular and molecular mechanisms underlying gut microbiota-mediated impact on liver disease. We also summarize the advancement of gut microbiota-based therapeutic strategies in the control of liver diseases.
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Affiliation(s)
- Xiaoqiang Qi
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
- Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
- VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
- Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
- VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
| | - Joseph Stenberg
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | - Rahul Dey
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | - Leslie Fogwe
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | | | - Eric T Kimchi
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
- Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
- VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
| | - Kevin F Staveley-O'Carroll
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
- Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
- VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
| | - Guangfu Li
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
- Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
- VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
- Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, United States
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