Identification and Analysis of Gut Microbiota and Functional Metabolism in Decompensated Cirrhosis with Infection |
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| Authors: | Cyriac Abby Philips Rizwan Ahamed Jinsha K.P. Abduljaleel Sasidharan Rajesh Philip Augustine |
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| Affiliation: | 1.Clinical and Translational Hepatology, Monarch Liver Laboratory, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, Kerala, India;2.Gastroenterology and Advanced GI Endoscopy, Center for Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva, Kerala, India;3.Diagnostic and Interventional Gastroenterology and Hepatology, Center for Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva, Kerala, India |
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| Abstract: | Background and AimsIntestinal 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.MethodsWe 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 comparisons. Conet/Cytoscape was utilized to identify significant non-random patterns of bacterial copresence and mutual exclusion for clinical events.ResultsGenera 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.ConclusionsSpecific 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. |
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| Keywords: | Microbiome Portal hypertension Sepsis Acute-on-chronic liver failure Multidrug resistance |
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