From Gut to Blood: Spatial and Temporal Pathobiome Dynamics during Acute Abdominal Murine Sepsis

Abdominal sepsis triggers the transition of microorganisms from the gut to the peritoneum and bloodstream. Unfortunately, there is a limitation of methods and biomarkers to reliably study the emergence of pathobiomes and to monitor their respective dynamics. Three-month-old CD-1 female mice underwen...

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Main Authors: Christina Hartwig, Susanne Drechsler, Yevhen Vainshtein, Madeline Maneth, Theresa Schmitt, Monika Ehling-Schulz, Marcin Osuchowski, Kai Sohn
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/11/3/627
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author Christina Hartwig
Susanne Drechsler
Yevhen Vainshtein
Madeline Maneth
Theresa Schmitt
Monika Ehling-Schulz
Marcin Osuchowski
Kai Sohn
author_facet Christina Hartwig
Susanne Drechsler
Yevhen Vainshtein
Madeline Maneth
Theresa Schmitt
Monika Ehling-Schulz
Marcin Osuchowski
Kai Sohn
author_sort Christina Hartwig
collection DOAJ
description Abdominal sepsis triggers the transition of microorganisms from the gut to the peritoneum and bloodstream. Unfortunately, there is a limitation of methods and biomarkers to reliably study the emergence of pathobiomes and to monitor their respective dynamics. Three-month-old CD-1 female mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Serial and terminal endpoint specimens were collected for fecal, peritoneal lavage, and blood samples within 72 h. Microbial species compositions were determined by NGS of (cell-free) DNA and confirmed by microbiological cultivation. As a result, CLP induced rapid and early changes of gut microbial communities, with a transition of pathogenic species into the peritoneum and blood detected at 24 h post-CLP. NGS was able to identify pathogenic species in a time course-dependent manner in individual mice using cfDNA from as few as 30 microliters of blood. Absolute levels of cfDNA from pathogens changed rapidly during acute sepsis, demonstrating its short half-life. Pathogenic species and genera in CLP mice significantly overlapped with pathobiomes from septic patients. The study demonstrated that pathobiomes serve as reservoirs following CLP for the transition of pathogens into the bloodstream. Due to its short half-life, cfDNA can serve as a precise biomarker for pathogen identification in blood.
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spelling doaj.art-d346c55ff0bc488eb91ccb1d9479fec02023-12-01T01:21:54ZengMDPI AGMicroorganisms2076-26072023-02-0111362710.3390/microorganisms11030627From Gut to Blood: Spatial and Temporal Pathobiome Dynamics during Acute Abdominal Murine SepsisChristina Hartwig0Susanne Drechsler1Yevhen Vainshtein2Madeline Maneth3Theresa Schmitt4Monika Ehling-Schulz5Marcin Osuchowski6Kai Sohn7Innovation Field In-Vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, GermanyLudwig Boltzmann Institute for Traumatology the Research Centre in Cooperation with AUVA, 1200 Vienna, AustriaInnovation Field In-Vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, GermanyInnovation Field In-Vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, GermanyInnovation Field In-Vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, GermanyFunctional Microbiology, Department of Pathobiology, Institute of Microbiology, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaLudwig Boltzmann Institute for Traumatology the Research Centre in Cooperation with AUVA, 1200 Vienna, AustriaInnovation Field In-Vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, GermanyAbdominal sepsis triggers the transition of microorganisms from the gut to the peritoneum and bloodstream. Unfortunately, there is a limitation of methods and biomarkers to reliably study the emergence of pathobiomes and to monitor their respective dynamics. Three-month-old CD-1 female mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Serial and terminal endpoint specimens were collected for fecal, peritoneal lavage, and blood samples within 72 h. Microbial species compositions were determined by NGS of (cell-free) DNA and confirmed by microbiological cultivation. As a result, CLP induced rapid and early changes of gut microbial communities, with a transition of pathogenic species into the peritoneum and blood detected at 24 h post-CLP. NGS was able to identify pathogenic species in a time course-dependent manner in individual mice using cfDNA from as few as 30 microliters of blood. Absolute levels of cfDNA from pathogens changed rapidly during acute sepsis, demonstrating its short half-life. Pathogenic species and genera in CLP mice significantly overlapped with pathobiomes from septic patients. The study demonstrated that pathobiomes serve as reservoirs following CLP for the transition of pathogens into the bloodstream. Due to its short half-life, cfDNA can serve as a precise biomarker for pathogen identification in blood.https://www.mdpi.com/2076-2607/11/3/627cecal ligation punctureCLPgut microbiomecell-free DNApathogen liquid biopsysepsis
spellingShingle Christina Hartwig
Susanne Drechsler
Yevhen Vainshtein
Madeline Maneth
Theresa Schmitt
Monika Ehling-Schulz
Marcin Osuchowski
Kai Sohn
From Gut to Blood: Spatial and Temporal Pathobiome Dynamics during Acute Abdominal Murine Sepsis
Microorganisms
cecal ligation puncture
CLP
gut microbiome
cell-free DNA
pathogen liquid biopsy
sepsis
title From Gut to Blood: Spatial and Temporal Pathobiome Dynamics during Acute Abdominal Murine Sepsis
title_full From Gut to Blood: Spatial and Temporal Pathobiome Dynamics during Acute Abdominal Murine Sepsis
title_fullStr From Gut to Blood: Spatial and Temporal Pathobiome Dynamics during Acute Abdominal Murine Sepsis
title_full_unstemmed From Gut to Blood: Spatial and Temporal Pathobiome Dynamics during Acute Abdominal Murine Sepsis
title_short From Gut to Blood: Spatial and Temporal Pathobiome Dynamics during Acute Abdominal Murine Sepsis
title_sort from gut to blood spatial and temporal pathobiome dynamics during acute abdominal murine sepsis
topic cecal ligation puncture
CLP
gut microbiome
cell-free DNA
pathogen liquid biopsy
sepsis
url https://www.mdpi.com/2076-2607/11/3/627
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