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Identification and Analysis of Gut Microbiota and Functional Metabolism in Decompensated Cirrhosis with Infection

Journal of Clinical and Translational Hepatology 2023年第1期11卷 15-25页

作者： Cyriac Abby philips Rizwan Ahamed jinsha k.p.abduljaleel Sasidharan Rajesh philip Augustine Clinical and Translational Hepatology Monarch Liver LaboratoryThe Liver InstituteCenter of Excellence in GI SciencesRajagiri HospitalAluvaKeralaIndia Gastroenterology and Advanced GI Endoscopy Center for Excellence in Gastrointestinal SciencesRajagiri HospitalAluvaKeralaIndia Diagnostic and Interventional Gastroenterology and Hepatology Center for Excellence in Gastrointestinal SciencesRajagiri HospitalAluvaKeralaIndia

Background and Aims:Intestinal dysbiosis play a role in the adverse outcomes of sepsis and septic shock.However,variations in bacterial diversity and microbiota-related functional metabolic alterations within the gut microbiome in decompensated cirrhosis(DC)patients with infection remain unknown.Methods:We conducted 16-srRNA sequencing on stool samples(n=51:sepsis,27/no sepsis,24)collected from consecutive DC patients upon admission.Bacterial diversity,significant taxa,and respective metabolic profiling were performed based on subgroup ***/Cytoscape was utilized to identify significant non-random patterns of bacterial copresence and mutual exclusion for clinical events.Results:Genera associated with pathogenicity in conditions of immune exhaustion(Corynebacterium,Lautropia)were predominant in patients with sepsis.Metabolic pathways associated with oxidative stress and endotoxemia[lipopolysaccharide(LpS)synthesis and sulfur relay]were significantly upregulated in sepsis.Specific taxa were associated with sites of infection in DC patients.protective oxidant pathways that increase glutathione were upregulated in those without sepsis.Gammaproteobacteria family of sulfur-metabolizing bacteria,exaggeration of orally predominant pathogens(prevotella),and pathways of severe LpS-related hyperinflammatory stress were notable in those with interleukin-6 levels>1,000 pg/dL.pathogenic genera related to an immune deficient state was significant in DC with≥2 infection episodes.Megamonas was associated with survival during the same admission.Conclusions:Specific gut microbiota and their metabolites were associated with sepsis and related events in patients with DC.Identifying beneficial strains that reduce immune exhaustion and supplementation of favorable metabolites could improve therapeutics for DC and sepsis,for which larger prospective,well controlled population-based studies remain an unmet need.

关键词： Microbiome portal hypertension Sepsis Acute-on-chronic liver failure Multidrug resistance

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Clinical outcomes and gut microbiota analysis of severe alcohol-associated hepatitis patients undergoing healthy donor fecal transplant or pentoxifylline therapy:single-center experience from kerala

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Gastroenterology Report 2022年第1期10卷 566-574页

作者： Cyriac Abby philips Rizwan Ahamed Sasidharan Rajesh Shobhit Singh Ajit Tharakan jinsha k.abduljaleel philip Augustine Clinical and Translational Hepatology The Liver InstituteCenter of Excellence in GI SciencesRajagiri HospitalChunangamvelyAluvaErnakulamKeralaIndia Monarch Liver Laboratory The Liver InstituteCenter of Excellence in GI SciencesRajagiri HospitalChunangamvelyAluvaErnakulamKeralaIndia Department of Gastroenterology and Advanced GI Endoscopy Center of Excellence in GI SciencesRajagiri HospitalChunangamvelyAluvaErnakulamKeralaIndia Diagnostic and Interventional Radiology Center of Excellence in GI SciencesRajagiri HospitalChunangamvelyAluvaErnakulamKeralaIndia

Background Severe alcohol-associated hepatitis(SAH)patients with infections have a high short-term mortality rate.Gut microbiota dysbiosis plays an important role in the pathogenesis of SAH.preliminary studies have demonstrated long-term benefits with healthy donor fecal microbiota transplantation(FMT).Data on FMT compared with pentoxifylline for SAH and relevant gut microbial changes are lacking in literature.Methods From January 2019 to February 2021,retrospective analysis of a single hospital’s records revealed 47 SAH patients undergoing FMT(100mL/day via nasoduodenal tube for 7days)and 25matched patients receiving pentoxifylline(400mg/8 h for 28days).The primary end point was a 6-month survival rate.Secondary end points included incidence of ascites,hepatic encephalopathy,infections,acute kidney injury,and gutmicrobiota changes between post-therapy groups.Biomarker discovery and network analysis were also performed to identify significant taxa of gutmicrobiota in post-treatment groups in retrospectively stored stool samples.Results All were males.The 6-month survival rate was higher in the patients undergoing FMT than in patients receiving pentoxifylline(83.0%vs 56.0%,p=0.012).At the end of 6-month follow-up,the incidences of clinically significant ascites(56.0%vs 25.5%,p=0.011),hepatic encephalopathy(40.0%vs 10.6%,p=0.003),and critical infections(52.0%vs 14.9%,ppatients administered pentoxifylline were significantly higher than those in patients treated with FMT.At 3 months,biomarker analysis revealed a significant abundance of Bifidobacterium and Eggerthella in the FMT group and the pentoxifylline group,respectively.At 6 months,Bifidobacterium in the FMT group and pathogenic Aerococcaceae in the pentoxifylline group were notable.Network analysis showed beneficial taxa(Bifidobacterium)as a central influencer in those undergoing FMT at 6 months.Conclusions Healthy donor FMT improved survival rate and reduced liver-related complications compared with pentoxifylline.These clinical benefits were associ

关键词： fecal microbiota stool transplant alcoholic hepatitis liver transplant dysbiosis

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