Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis

Background & Aims Altered gut microbiota is associated with poor outcomes in cirrhosis, including infections and hepatic encephalopathy (HE). However, the role of bacterial virulence factors (VFs) is unclear. Aim: Define association of VFs with cirrhosis severity and infections, their linkage wi...

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Autores principales:	Jasmohan S Bajaj, Amirhossein Shamsaddini, Chathur Acharya, Andrew Fagan, Masoumeh Sikaroodi, Edith Gavis, Sara McGeorge, Alexander Khoruts, Michael Fuchs, Richard K Sterling, Hannah Lee, Patrick M Gillevet
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	hospitalizations death infections enterococcus fecal microbiota transplant Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/ff88e34907614f2796426c1ee8a5b73b
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spelling	oai:doaj.org-article:ff88e34907614f2796426c1ee8a5b73b2021-11-11T14:23:42ZMultiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis1949-09761949-098410.1080/19490976.2021.1993584https://doaj.org/article/ff88e34907614f2796426c1ee8a5b73b2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/19490976.2021.1993584https://doaj.org/toc/1949-0976https://doaj.org/toc/1949-0984Background & Aims Altered gut microbiota is associated with poor outcomes in cirrhosis, including infections and hepatic encephalopathy (HE). However, the role of bacterial virulence factors (VFs) is unclear. Aim: Define association of VFs with cirrhosis severity and infections, their linkage with outcomes, and impact of fecal microbiota transplant (FMT). Methods VF abundances were determined using metagenomic analysis in stools from controls and cirrhosis patients (compensated, HE-only, ascites-only, both and infected). Patients were followed for 90-day hospitalizations and 1-year death. Stool samples collected before/after a placebo-controlled FMT trial were also analyzed. Bacterial species and VFs for all species and selected pathogens (Escherichia, Klebsiella, Pseudomonas, Staphylococcus, Streptococcus, and Enterococcus spp) were compared between groups. Multi-variable analyses were performed for clinical biomarkers and VFs for outcome prediction. Changes in VFs pre/post-FMT and post-FMT/placebo were analyzed. Results: We included 233 subjects (40 controls, 43 compensated, 30 HE-only, 20 ascites-only, 70 both, and 30 infected). Decompensated patients, especially those with infections, had higher VFs coding for siderophores, biofilms, and adhesion factors versus the rest. Biofilm and adhesion VFs from Enterobacteriaceae and Enterococcus spp associated with death and hospitalizations independent of clinical factors regardless of when all VFs or selected pathogens were analyzed. FMT was associated with reduced VF post-FMT versus pre-FMT and post-placebo groups. Conclusions Virulence factors from multiple species focused on adhesion and biofilms increased with decompensation and infections, associated with death and hospitalizations independent of clinical factors, and were attenuated with FMT. Strategies focused on targeting multiple virulence factors could potentially impact outcomes in cirrhosis. Presentations Portions of this manuscript were an oral presentation in the virtual International Liver Congress 2021 Abbreviations VF: virulence factors, HE: hepatic encephalopathy, FMT: Fecal microbiota transplant, PPI: proton pump inhibitors, LPS: lipopolysaccharides, VFDB: Virulence factor database, OTU: operational taxonomic units, SBP: spontaneous bacterial peritonitis, UTI: urinary tract infections, MRSA: methicillin resistant Staphylococcus aureus, VRE: vancomycin-resistant Enterococcus, MAAsLin2: Microbiome Multivariable Associations with Linear Models, LPS: lipopolysaccharides, AKI: acute kidney injuryJasmohan S BajajAmirhossein ShamsaddiniChathur AcharyaAndrew FaganMasoumeh SikaroodiEdith GavisSara McGeorgeAlexander KhorutsMichael FuchsRichard K SterlingHannah LeePatrick M GillevetTaylor & Francis Grouparticlehospitalizationsdeathinfectionsenterococcusfecal microbiota transplantDiseases of the digestive system. GastroenterologyRC799-869ENGut Microbes, Vol 13, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hospitalizations death infections enterococcus fecal microbiota transplant Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	hospitalizations death infections enterococcus fecal microbiota transplant Diseases of the digestive system. Gastroenterology RC799-869 Jasmohan S Bajaj Amirhossein Shamsaddini Chathur Acharya Andrew Fagan Masoumeh Sikaroodi Edith Gavis Sara McGeorge Alexander Khoruts Michael Fuchs Richard K Sterling Hannah Lee Patrick M Gillevet Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis
description	Background & Aims Altered gut microbiota is associated with poor outcomes in cirrhosis, including infections and hepatic encephalopathy (HE). However, the role of bacterial virulence factors (VFs) is unclear. Aim: Define association of VFs with cirrhosis severity and infections, their linkage with outcomes, and impact of fecal microbiota transplant (FMT). Methods VF abundances were determined using metagenomic analysis in stools from controls and cirrhosis patients (compensated, HE-only, ascites-only, both and infected). Patients were followed for 90-day hospitalizations and 1-year death. Stool samples collected before/after a placebo-controlled FMT trial were also analyzed. Bacterial species and VFs for all species and selected pathogens (Escherichia, Klebsiella, Pseudomonas, Staphylococcus, Streptococcus, and Enterococcus spp) were compared between groups. Multi-variable analyses were performed for clinical biomarkers and VFs for outcome prediction. Changes in VFs pre/post-FMT and post-FMT/placebo were analyzed. Results: We included 233 subjects (40 controls, 43 compensated, 30 HE-only, 20 ascites-only, 70 both, and 30 infected). Decompensated patients, especially those with infections, had higher VFs coding for siderophores, biofilms, and adhesion factors versus the rest. Biofilm and adhesion VFs from Enterobacteriaceae and Enterococcus spp associated with death and hospitalizations independent of clinical factors regardless of when all VFs or selected pathogens were analyzed. FMT was associated with reduced VF post-FMT versus pre-FMT and post-placebo groups. Conclusions Virulence factors from multiple species focused on adhesion and biofilms increased with decompensation and infections, associated with death and hospitalizations independent of clinical factors, and were attenuated with FMT. Strategies focused on targeting multiple virulence factors could potentially impact outcomes in cirrhosis. Presentations Portions of this manuscript were an oral presentation in the virtual International Liver Congress 2021 Abbreviations VF: virulence factors, HE: hepatic encephalopathy, FMT: Fecal microbiota transplant, PPI: proton pump inhibitors, LPS: lipopolysaccharides, VFDB: Virulence factor database, OTU: operational taxonomic units, SBP: spontaneous bacterial peritonitis, UTI: urinary tract infections, MRSA: methicillin resistant Staphylococcus aureus, VRE: vancomycin-resistant Enterococcus, MAAsLin2: Microbiome Multivariable Associations with Linear Models, LPS: lipopolysaccharides, AKI: acute kidney injury
format	article
author	Jasmohan S Bajaj Amirhossein Shamsaddini Chathur Acharya Andrew Fagan Masoumeh Sikaroodi Edith Gavis Sara McGeorge Alexander Khoruts Michael Fuchs Richard K Sterling Hannah Lee Patrick M Gillevet
author_facet	Jasmohan S Bajaj Amirhossein Shamsaddini Chathur Acharya Andrew Fagan Masoumeh Sikaroodi Edith Gavis Sara McGeorge Alexander Khoruts Michael Fuchs Richard K Sterling Hannah Lee Patrick M Gillevet
author_sort	Jasmohan S Bajaj
title	Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis
title_short	Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis
title_full	Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis
title_fullStr	Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis
title_full_unstemmed	Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis
title_sort	multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/ff88e34907614f2796426c1ee8a5b73b
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_version_	1718439002632093696

Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis

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