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From Gut to Blood: Spatial and Temporal Pathobiome Dynamics during Acute Abdominal Murine Sepsis
Christina Hartwig1,2, Susanne Drechsler3, Yevhen Vainshtein1
1Innovation Field In-Vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany.
Abstract:
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.
Insights
Abdominal sepsis causes gut microbes to enter the bloodstream. Cell-free DNA (cfDNA) in blood offers a rapid biomarker for identifying these pathogens during sepsis.
Area of Science:
- Microbiology
- Immunology
- Genomics
Background:
- Abdominal sepsis facilitates microbial translocation from the gut to sterile sites.
- Current methods for studying pathobiomes and their dynamics are limited.
- Reliable biomarkers are needed to track microbial shifts during sepsis.
Purpose of the Study:
- To investigate the dynamics of microbial translocation in abdominal sepsis.
- To evaluate next-generation sequencing (NGS) of cell-free DNA (cfDNA) for pathogen detection.
- To identify potential biomarkers for monitoring sepsis progression.
Main Methods:
- Cecal ligation and puncture (CLP) model in mice to induce abdominal sepsis.
- Serial sampling of fecal, peritoneal lavage, and blood specimens within 72 hours.
- Next-generation sequencing (NGS) of cfDNA for microbial composition analysis.
- Microbiological cultivation for confirmation of findings.
Main Results:
- CLP rapidly altered gut microbial communities, with pathogen translocation to peritoneum and blood by 24 hours.
- NGS detected pathogenic species in blood cfDNA within 72 hours, even with small sample volumes.
- Pathogen cfDNA levels correlated with sepsis dynamics, showing a short half-life.
- Identified pathobiomes in mice showed significant overlap with those in human septic patients.
Conclusions:
- Pathobiomes act as reservoirs for pathogen dissemination during sepsis.
- cfDNA in blood is a sensitive and dynamic biomarker for rapid pathogen identification in sepsis.
- NGS of cfDNA enables timely monitoring of microbial dynamics in sepsis.
