{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T15:02:42Z","timestamp":1771945362711,"version":"3.50.1"},"reference-count":19,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background and Aims: Sepsis drives mortality in cirrhosis, yet the gut antimicrobial resistance (AMR) landscape remains unmapped in high-burden settings like India. This study aimed to integrate shotgun metagenomics with deep immunophenotyping to define the gut\u2013immune\u2013resistome axis and correlate specific microbial and genetic signatures with clinical outcomes in decompensated cirrhosis. Methods: We analysed 78 hospitalized patients with cirrhosis using stool shotgun metagenomics, multiplex cytokine arrays, and flow cytometry. The microbiome and resistome (AMR genes) were mapped and correlated with disease severity, immune function (monocyte HLA-DR, neutrophil CD64), and clinical endpoints including mortality. Results: Disease severity was characterized by a \u201cGram-negative bloom\u201d (Klebsiella) alongside pathogenic Enterococcus expansion and novel markers: Clostridium sp. C5-48 (severe decompensation) and Sutterella (ascites). A specific, dense resistome predicted adverse outcomes; the quinolone-resistance gene QnrB4 correlated with mortality and immune paralysis, while the carbapenemase OXA-833 gene was linked to gastrointestinal bleeding. Notably, the commensal Ligilactobacillus salivarius was associated with systemic inflammatory cytokines. Conclusions: This study reveals a \u201cpathogenic ecosystem\u201d in Indian decompensated cirrhosis where the resistome is intrinsically linked to host immune failure. The identification of specific prognostic markers (QnrB4, OXA-833) and inflammatory associations with L. salivarius challenges generic probiotic use and underscores the urgent need for precision, resistome-targeted therapies.<\/jats:p>","DOI":"10.3390\/pathogens15030241","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T13:53:20Z","timestamp":1771941200000},"page":"241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Insights on Clinical Outcomes Using Integrated Shotgun Metagenomic Profiling of the Gut Microbiome, Resistome, and Host Immune-Inflammatory Response in Hospitalized Patients with Decompensated Cirrhosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Cyriac Abby","family":"Philips","sequence":"first","affiliation":[{"name":"Department of Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva 683112, Kerala, India"},{"name":"Clinical Research Division, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0511-5002","authenticated-orcid":false,"given":"Tharun Tom","family":"Oommen","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva 683112, Kerala, India"},{"name":"Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3570-3465","authenticated-orcid":false,"given":"Arif Hussain","family":"Theruvath","sequence":"additional","affiliation":[{"name":"Clinical Research Division, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6960-4627","authenticated-orcid":false,"given":"Aryalakshmi","family":"Sreemohan","sequence":"additional","affiliation":[{"name":"Clinical Research Division, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1469-9934","authenticated-orcid":false,"given":"Ambily","family":"Baby","sequence":"additional","affiliation":[{"name":"Clinical Research Division, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ansu Abu","family":"Alex","sequence":"additional","affiliation":[{"name":"Department of Advanced Flow Cytometry Immunophenotyping Facility, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunitha","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Services, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunitha Mary","family":"John","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rizwan","family":"Ahamed","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajit","family":"Tharakan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Augustine","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital, Aluva 683112, Kerala, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.4254\/wjh.v12.i8.451","article-title":"Update on diagnosis and management of sepsis in cirrhosis: Current advances","volume":"12","author":"Philips","year":"2020","journal-title":"World J. 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