Work Description

Date: 12 June, 2024

Dataset Title: Data for Early Sepsis-Mediated Metabolic Changes in Blood, Kidney, and Liver Precede Clinical Evidence of Organ Dysfunction

Dataset Creators:
Marc McCann
Christopher Fry
Michael Maile
Evan Farkash
Brandon Cummings
Thomas Flott
Laura McLellan
Michael Puskarich
Alan Jones
Kathleen Stringer

Dataset Contact:
Kathleen Stringer, [email protected]

Funding:
National Institute of General Medical Sciences (NIGMS) and the National Heart, Lung, and Blood Institute (NHLBI): R35GM136312, R01HL144599, K24HL159247 and R01GM103799.

Research Overview:
Organ-specific metabolic pathways, including those related to mitochondrial metabolism, could provide insight to mechanisms underlying sepsis-induced organ dysfunction. However, it remains unclear if metabolic changes precede or if they result from organ dysfunction. We determined if blood levels of the mitochondrial metabolites acetylcarnitine and L-carnitine correlate with organ-specific signals of sepsis-induced dysfunction. To achieve this goal, we performed a series of translational analyses of two cohorts of human sepsis and experiments using a murine model of polymicrobial sepsis. We evaluated the association between mitochondrial metabolites and clinical indices of organ function. We found that in the blood of patients with sepsis or septic shock, metabolic indices of dysfunctional mitochondrial beta-oxidation that were correlated with clinical measures of renal and liver dysfunction. The relevance of these findings was corroborated in an experimental model that showed distinct patterns of change in organ metabolism that correlated with the blood acetylcarnitine to L-carnitine ratio. In addition, sepsis-induced changes in organ metabolism were distinct in the liver and kidney highlighting the unique energy economies of each organ. Importantly, these metabolic changes preceded histological evidence of cellular apoptosis. In conclusion, sepsis-induced disruption in blood levels of specific metabolites could serve as more reliable indicators of early organ dysfunction than those we presently use. These early metabolite signals provide mechanistic insights to altered metabolism that may hold the key to timely identification of impending organ dysfunction. This could lead to strategies directed at the prevention of sepsis-induced organ failure.

Methodology:
The data from the sepsis cohort were collected under an IRB-approved protocol (HUM00190592). The data from the septic shock cohort were previously generated as part of another study under “not regulated” protocol (HUM00104311). Metabolomics data for both studies were generated at the University of Michigan. The cecal-ligation-puncture mouse model experiments were conducted in Dr. Stringer's laboratory under an IACUC-approved protocol (PRO00011140). Metabolomics for this study were also generated at the University of Michigan as where other clinical measurements.

Files contained here:
-CLP mouse data.csv: kidney and liver freeze clamp metabolomics and TUNEL assay results from cecal-ligation-puncture (CLP) murine experiments

-Sepsis cohort data.csv: demographic, clinical data, and plasma metabolomics data

-Septic shock cohort.csv: demographic, clinical data and serum metabolomics data

There is also a corresponding data dictionary .csv for each data file.

Related publication(s):
Early Sepsis-Mediated Metabolic Changes in Blood, Kidney, and Liver Precede Clinical Evidence of Organ Dysfunction (Forthcoming)

Use and Access:
This data set is made available under a Creative Commons Attribution-Noncommercial license (CC BY-NC 4.0).

To Cite Data:
Stringer, K. Sepsis cohort-metabolomics & demographic dataset, Septic shock cohort-metabolomics & demographic dataset, Cecal ligation & puncture murine model- renal & liver metabolomics dataset [Data set], University of Michigan - Deep Blue Data. https://doi.org/10.7302/8fyq-3f56