1443: Omic Biomarkers in Traumatic Brain Injury Reveal Increased Gut Permeability with Granulopoiesis Loss

Document Type

Conference Proceeding

Publication Date

1-2025

Publication Title

Critical Care Medicine

Abstract

Introduction: Traumatic brain injury (TBI) is a major contributor to disability and death among children. We hypothesize that using metabolomics in conjunction with RNA sequencing (Metabolo-transcriptomics) we will identify biomarkers and discover novel targets for diagnosis and therapy.

Methods: After IRB approval (2021-096) and informed consent, pediatric patients (17 TBI and 10 controls) aged ≥ 1 and ≤ 21 were enrolled with severe TBI (GCS ≤ 8). Whole blood PAXgene tubes and plasma were collected at multiple time points along with clinical variables from the medical record. RNA was analyzed as paired-end 150 base pair reads of around 30 million reads per sample. Reads were aligned to the human transcriptome Gencode 45 using Salmon and species recognition transcriptomes using the KRAKEN2 index alignment. We employed liquid chromatography-mass spectrometry (LC-MS/MS) and 1H NMR to biochemically profile the blood plasma. All data were combined using a variety of machine learning modalities.

Results: Clinical data revealed white cell counts (WBC) with SD, of 16861±7425/uL, and absolute neutrophil count (ANC) at 11515±5194/uL upon admission. At day 2, WBC of 10949±44089/uL, ANC of 7447±2185/uL. Day 8, WBC of 10815±4534/uL and ANC of 6760±1356/uL. At admission, TBI patients had 22 high-confidence transcripts elevated that returned to control levels by day 8. These were enriched for non-protein coding transcripts such as lncRNA and retained intron with many unique to bone marrow-specific expressions and some immune cell activation. Metabolo-transcriptomic data revealed that the regulation of granulopoiesis is lost in patients with severe head trauma. Three patients showed elevation of 8 bacterial species of normal gut flora at days 0 and 3 including E.coli, Clostridium scindens, and Oscillibacter hominis. At day 8, patients had an elevation of 28 high-confidence transcripts enriched for protein coding with 9 involved in erythropoietin biology.

Conclusions: The metabolo-transcrisptomic approach applied herein has the potential to uncover novel disease signatures that could be used to develop a precision-modeled method for the diagnosis and care of pediatric TBI.

Volume

53

Issue

1

Comments

The Society of Critical Care Medicine's 54th Critical Care Congress, February 23-25, 2025, Orlando, FL.

DOI

10.1097/01.ccm.0001104436.11047.11

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