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rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

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World Journal of Hepatology 2024年第1期16卷 75-90页

作者： Matheus Truccolo Michalczuk Larisse Longo Melina Belén Keingeski Bruno de Souza Basso Gabriel Tayguara Silveira Guerreiro Jessica T Ferrari JoséEduardo Vargas Cláudia P Oliveira Carolina Uribe-Cruz Carlos Thadeu Schmidt Cerski Eduardo Filippi-Chiela Mário ReisÁlvares-da-Silva Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Laboratory of Inflammatory and Neoplastic Cells Universidade Federal do ParanáParaná81530900Brazil Department of Gastroenterology(LIM07) Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Unit of Surgical Pathology Hospital de Clinicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Department of Morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90.050-170Rio Grande do SulBrazil Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)ResearcherBrasília 71.605-001Brazil

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in *** Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were *** All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop *** animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the *** opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-*** with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis throu

关键词： Animal model Autophagy Epigenetic Hepatocellular carcinoma Metabolic dysfunction-associated steatotic liver disease rifaximin

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rifaximin vs conventional oral therapy for hepatic encephalopathy:A meta-analysis

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World Journal of Gastroenterology 2012年第8期18卷 767-777页

作者： Karim M Eltawil Marie Laryea Kevork Peltekian Michele Molinari Department of Surgery and Transplantation Queen Elizabeth Ⅱ Health Sciences Center Dalhousie University Department of Medicine Hepatology and Transplantation Queen Elizabeth Ⅱ Health Sciences Center Dalhousie University

AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents. METHODS: We performed a systematic review and random effects meta-analysis of all eligible trials identifi ed through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients. RESULTS: The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics[odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profi le (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical signifi cance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any signifi cant difference in the above fi ndings. CONCLUSION: rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profi le.

关键词： Hepatic encephalopathy Lactulose Neo-mycin Non-absorbable disaccharides rifaximin

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rifaximin in the treatment of inflammatory bowel disease

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World Journal of Gastroenterology 2011年第42期17卷 4643-4646页

作者： Mario Guslandi Gastroenterology Unit S Raffaele University Hospital

The gut microbiota plays a role in promoting and maintaining inflammation in inflammatory bowel diseases （IBD）, hence the rationale for the use of antibiotics in the treatment of those disorders. Antibiotics, however, may induce untoward effects, especially during longterm therapy. rifaximin α polymer is an antibacterial agent that is virtually unabsorbed after oral administration and is devoid of systemic side effects. rifaximin has provided promising results in inducing remission of Crohn＇s disease （up to 69% in open studies and significantly higher rates than placebo in double blind trials） and ulcerative colitis （76% in open studies and significantly higher rates than placebo in controlled studies） and might also have a role in maintaining remission of ulcerative colitis and pouchitis. The potential therapeutic activity of rifaximin in IBD deserves to be further investigated and confirmed in larger, controlled studies. The optimal dosage still needs to be better defined.

关键词： Antibiotics Gut microbiota Inflammatorybowel disease rifaximin

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rifaximin improves survival in cirrhotic patients with refractory ascites: A real-world study

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World Journal of Gastroenterology 2020年第2期26卷 199-218页

作者： Xin-Yue Lv Hui-Guo Ding Jun-Fu Zheng Chun-Lei Fan Lei Li Department of Gastroenterology and Hepatology Beijing You An Hospital Capital Medical University

BACKGROUND rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with ***,few studies have investigated the effect of rifaximin in cirrhotic patients with refractory *** To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible *** A total of 75 cirrhotic patients with refractory ascites were enrolled in the study(50 in a rifaximin and 25 in a control group).Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics(19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics).All patients received conventional treatment for refractory ascites,while patients in the rifaximin group received oral rifaximin-α200 mg four times daily for at least 2 *** ascites grade,fasting weight,liver and kidney function,and inflammatory factors in the plasma were evaluated before and after *** addition,the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin *** patients were followed for 6 *** Compared with the control group,the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin(P=0.011 and 0.009,respectively).The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group(P=0.048).The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group(P=0.024).The abundance of Roseburia,Haemophilus,and Prevotella was significantly reduced after rifaximin treatment,while the abundance of Lachnospiraceae_noname,Subdoligranulum,and Dorea decreased and the abundance of Co

关键词： rifaximin Cirrhosis Refractory ascites Inflammatory factors Gut microbiota Metagenomics sequencing

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rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity

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World Journal of Gastroenterology 2017年第47期23卷 8355-8366页

作者： Kosuke Kaji Hiroaki Takaya Soichiro Saikawa Masanori Furukawa Shinya Sato Hideto Kawaratani Mitsuteru Kitade Kei Moriya Tadashi Namisaki Takemi Akahane Akira Mitoro Hitoshi Yoshiji Third Department of Internal Medicine Nara Medical University

AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic *** Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene *** Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.

关键词： gut microbiome Hepatic encephalopathy Liver cirrhosis Endotoxin rifaximin

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rifaximin Prevents Intestinal Barrier Dysfunction and Alleviates Liver Injury in MCT-induced HSOS Mice

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Current Medical Science 2023年第6期43卷 1183-1194页

作者： Yan-yun SHU Li-lin HU Ling YANG Hui-kuan CHU Jin YE Yu JIN Division of Gastroenterology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Ultrasound The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430000China

Objective rifaximin is an effective component of treatment strategies for liver and intestinal ***,the efficacy of rifaximin in hepatic sinusoidal obstruction syndrome(HSOS)has not been *** present study aimed to investigate the efficacy and mechanism of rifaximin in *** An HSOS model was established in mice through the administration of monocrotaline(MCT,800 mg/kg),and part of the HSOS mice were intragastrically administered with ***,the efficacy of rifaximin in HSOS was evaluated based on the liver pathological findings,liver proinflammatory cytokines,and alanine aminotransferase and aspartate aminotransferase *** Ussing chamber was used to evaluate the intestinal permeability,and tight junction(TJ)proteins were measured by Western blotting and real-time polymerase chain reaction to evaluate the intestinal barrier ***,the serum proinflammatory cytokine levels were evaluated by enzyme-linked immunosorbent ***,an in vitro experiment was performed to determine the relationship between rifaximin and TJ *** rifaximin effectively alleviated the MCT-induced HSOS liver injury,suppressed the expression of liver proinflammatory cytokines,and reduced the serum levels of tumor necrosis factor-alpha and ***,rifaximin reduced the intestinal permeability,improved the intestinal barrier integrity,and promoted the expression of TJ *** The results revealed that the intestinal barrier integrity was destroyed in MCT-induced *** significant alleviation of MCT-induced HSOS induced by rifaximin might be correlated to the repairment of intestinal barrier integrity via the regulation of the TJ protein expression.

关键词： rifaximin hepatic sinusoidal obstruction syndrome intestinal barrier tight junction proteins inflammation

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rifaximin for the prevention of spontaneous bacterial peritonitis

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World Journal of Gastroenterology 2012年第14期18卷 1700-1702页

作者： Georgios N Kalambokis Athanasia Mouzaki Maria Rodi Epameinondas V Tsianos The First Division of Internal Medicine and Hepato-Gastroenterology Unit Medical School of Ioannina45110 IoanninaGreece Division of Hematology Department of Internal MedicineMedical School26504 PatrasGreece

According to a review article by Biecker et al published in a previous issue of World Journal of Gastroenterology in March 2011,intestinal decontamination with norfloxacin remains the mainstay of primary prophylaxis of spontaneous bacterial peritonitis(SBP) at the expense of development of quinolone-resistant bacteria after long-term *** our research,the administration of a 4-wk regimen with rifaximin 1200 mg/d reduced significantly the ascitic neutrophil count in cirrhotic patients with sterile ascites in line with a significant decrease in plasma endotoxin *** observations concur with recent findings,showing a significantly reduced 5-year probability of SBP in cirrhotic patients taking rifaximin.

关键词： rifaximin Cirrhosis Ascites Spontaneous bacterial peritonitis

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Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms:Experience with rifaximin

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World Journal of Gastroenterology 2009年第21期15卷 2628-2631页

作者： Sergio Peralta Claudia Cottone Tiziana Doveri Piero Luigi Almasio Antonio Craxi Operative Unit of Gastroenterology and Hepatology

AIM： TO estimate the prevalence of small intestinal bacterial overgrowth （SIBO） in our geographical area （Western Sicily, Italy） by means of an observational study, and to gather information on the use of locally active, non-absorbable antibiotics for treatment of SIBO.METHODS： Our survey included 115 patients fulfilling the Rome II criteria for diagnosis of irritable bowel syndrome （IBS）; a total of 97 patients accepted to perform a breath test with lactulose （BTLact）, and those who had a positive test, received rifaximin （Normix , Alfa Wassermann） 1200 mg/d for 7 d; 3 wk after the end of treatment, the BTLact was repeated.RESULTS： Based on the BTLact results, SIBO was present in about 56% of IBS patients, and it was responsible for some IBS-related symptoms, such as abdominal bloating and discomfort, and diarrhoea. 1-wk treatment with rifaximin turned the BTLact to negative in about 50% of patients and significantly reduced the symptoms, especially in those patients with an alternated constipation/diarrhoea-variant IBS. CONCLUSION： SIBO should be always suspected in patients with IBS, and a differential diagnosis is done by means of a ＂breath test＂. rifaximin may represent a valid approach to the treatment of SIBO.

关键词： rifaximin Small intestinal bacterialovergrowth Irritable bowel syndrome Locally nonabsorbable antibiotics

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Patients with breath test positive are necessary to be identified from irritable bowel syndrome:a clinical trial based on microbiomics and rifaximin sensitivity

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Chinese Medical Journal 2022年第14期135卷 1716-1727页

作者： Zuojing Liu Shiwei Zhu Meibo He Mo Li Hui Wei Lu Zhang Qinghua Sun Qiong Jia Nan Hu Yuan Fang Lijin Song Chen Zhou Heqing Tao John Y Kao Huaiqiu Zhu Chung Owyang Liping Duan Department of Gastroenterology Peking University Third HospitalHaidian DistrictBeijing 100191China Department of Ultrasound Peking University Third HospitalHaidian DistrictBeijing 100191China Institute of Systems Biomedicine School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Department of Biomedical Engineering College of EngineeringPeking UniversityBeijing 100187China Division of Gastroenterology Department of Internal MedicineUniversity of Michigan Health System6520 MSRB ISPC 56821150 West Medical Center DriveAnn ArborMI 48109USA

Background:As a non-invasive and effective diagnostic method for small intestinal bacterial overgrowth(SIBO),wild-use of breath test(BT)has demonstrated a high comorbidity rate in patients with diarrhea-predominant irritable bowel syndrome(IBS-D)and *** overlapping with SIBO respond better to rifaximin therapy than those with IBS-D *** microbiota plays a critical role in both of these two *** aimed to determine the microbial difference between IBS-D overlapping with/without SIBO,and to study the underlying mechanism of its sensitivity to ***:Patients with IBS-D were categorized as BT-negative(IBSN)and BT-positive(IBSP).Healthy volunteers(BT-negative)were enrolled as healthy *** patients were clinically evaluated before and after rifaximin treatment(0.4 g bid,4 weeks).Blood,intestine,and stool samples were collected for cytokine assessment and gut microbial ***:Clinical complaints and microbial abundance were significantly higher in IBSP than in *** contrast,severe systemic inflammation and more active bacterial invasion function that were associated with enrichment of opportunistic pathogens were seen in *** symptoms of IBSP patients were relieved in different degrees after therapy,but the symptoms of IBSN rarely *** also found that the presence of IBSN-enriched genera(Enterobacter and Enterococcus)are unaffected by rifaximin ***:IBS-D patients overlapping with SIBO showed noticeably different fecal microbial composition and function compared with IBS-D *** better response to rifaximin in those comorbid patients might associate with their different gut microbiota,which suggests that BT is necessary before IBS-D diagnosis and use of ***:Chinese Clinical Trial Registry,ChiCTR1800017911.

关键词： Irritable bowel syndrome Small intestinal bacterial overgrowth Breath test Gut microbiota rifaximin

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Chronic bacterial prostatitis and irritable bowel syndrome： effectiveness of treatment with rifaximin followed by the probiotic VSL#3

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Asian Journal of Andrology 2014年第5期16卷 735-739,I0009页

作者： Enzo Vicari Sandro La Vignera Roberto Castiglione Rosita A Condorelli Lucia O Vicari Aldo E Calogero Section of Endocrinology Andrology and Internal Medicine Department of MedicaJ and Pediatric Sciences Master in Experimental and Clinical Medicine and Cellular Physiopathology University of Catania Catania Italy

This study was undertaken to evaluate the influence of treatment with rifaximin followed by the probiotic VSL#3 versus no treatment on the progression of chronic prostatitis toward chronic microbial prostate-vesiculitis （PV） or prostate-vesiculo-epididymitis （PVE）. A total of 106 selected infertile male patients with bacteriologically cured chronic bacterial prostatitis （CBP） and irritable bowel syndrome （IBS） were randomly prescribed rifaximin （200 mg, 2 tablets bid, for 7 days monthly for 12 months） and probiotic containing multiple strains VSL#3 （450 × 10^9 CFU per day） or no treatment. Ninety-five of them （89.6%） complied with the therapeutic plan and were included in this study. Group A = ＂6Tx/6-＂： treatment for the initial 6 and no treatment for the following 6 months （n = 26）; Group B = ＂12Tx＂： 12 months of treatment （n = 22）; Group C = ＂6-/6Tx＂： no treatment for the initial 6 months and treatment in the last 6 months （n = 23）; Group D = ＂12-＂： no treatment （n = 24）. The patients of Groups A = ＂6Tx/6-＂ and B = ＂12Tx＂ had the highest frequency of chronic prostatitis （88.5% and 86.4%, respectively）. In contrast, group ＂12-＂： patients had the lowest frequency of prostatitis （33.4%）. The progression of prostatitis into PV in groups ＂6Tx/6-＂（15.5%） and ＂6-/6Tx＂（13.6%） was lower than that found in the patients of group ＂12-＂（45.8%）. Finally, no patient of groups ＂6Tx/6-＂ and ＂6-/6Tx＂ had PVE, whereas it was diagnosed in 20.8% of group ＂12-＂ patients. Long-term treatment with rifaximin and the probiotic VSL#3 is effective in lowering the progression of prostatitis into more complicated forms of male accessory gland infections in infertile patients with bacteriologically cured CBP plus IBS.

关键词： chronic bacterial prostatitis irritable bowel syndrome probiotic VSL#3 prostate-vesiculitis prostate-vesiculo-epididymitis rifaximin

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