Journal article
INFLAMMATORY RESPONSES TO POLYMICROBIAL INTRA-ABDOMINAL SEPSIS ARE HIGHLY VARIABLE BUT STRONGLY CORRELATED TO ENTEROBACTERIACEAE OUTGROWTH
Shock (Augusta, Ga.), Vol.62(2), pp.275-285
08/01/2024
DOI: 10.1097/SHK.0000000000002402
PMCID: PMC11254550
PMID: 38888452
Abstract
Sepsis is a common, heterogeneous, and frequently lethal condition of organ dysfunction and immune dysregulation due to infection. The causes of its heterogeneity, including the contribution of the pathogen, remain unknown. Using cecal slurry, a widely used murine model of intraperitoneal polymicrobial sepsis, as well as 16S ribosomal RNA sequencing and measurement of immune markers, we performed a series of translational analyses to determine whether microbial variation in cecal slurry composition (representing intra-abdominal pathogens) mediated variation in septic response. We found wide variation in cecal slurry community composition that changed markedly over the 24-h course of infection. This variation in cecal slurry bacteria led to large variation in physiologic and inflammatory responses. Severity of inflammatory response was positively correlated with intraperitoneal enrichment with Enterobacteriaceae. Likewise, in a human cohort of patients with intra-abdominal abscesses, Enterobacteriaceae was also associated with increased inflammatory markers. Taken together, these data demonstrate that intra-abdominal Enterobacteriaceae drives inflammation in sepsis both in animal models and human subjects. More broadly, our results demonstrate that pathogen identity is a major driver of the host response in polymicrobial sepsis and should not be overlooked as a major source of phenotypic heterogeneity.
Details
- Title: Subtitle
- INFLAMMATORY RESPONSES TO POLYMICROBIAL INTRA-ABDOMINAL SEPSIS ARE HIGHLY VARIABLE BUT STRONGLY CORRELATED TO ENTEROBACTERIACEAE OUTGROWTH
- Creators
- Kale S. Bongers - Michigan MedicineRishi Chanderraj - University of MichiganHuiyin Deng - Michigan MedicineYujing Song - University of MichiganMichael W. Newstead - Michigan MedicineJoseph D. Metcalf - Michigan MedicineNicole R. Falkowski - Michigan MedicineNiyati Puranik - University of MichiganKatsuo Kurabayashi - New York UniversityRobert P. Dickson - Ann Arbor Center for Independent LivingBenjamin H. Singer - Michigan Medicine
- Resource Type
- Journal article
- Publication Details
- Shock (Augusta, Ga.), Vol.62(2), pp.275-285
- DOI
- 10.1097/SHK.0000000000002402
- PMID
- 38888452
- PMCID
- PMC11254550
- NLM abbreviation
- Shock
- ISSN
- 1073-2322
- eISSN
- 1540-0514
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 11
- Grant note
- University of Michigan (Biomedical Research Council Bridge Support) China Scholarship Council T32HL007749; K08AR083015; K24HL159247; R01HL144599; R33HL154249; R01AG074968 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA CBET 1931905 / National Science Foundation; National Science Foundation (NSF)
- Language
- English
- Date published
- 08/01/2024
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984696652202771
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