Whole-body volatile organic compound profiling reveals metabolic pathway perturbations in a murine polymicrobial sepsis model: a feasibility study.
- 1Department of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China.
- 2Department of Naval Nutrition and Food Hygiene, Faculty of Naval Medicine, Naval Medical University, Shanghai, China.
- 3Key Laboratory of Biological Defense, Ministry of Education, Naval Medical University, Shanghai, China.
Abstract
Sepsis rewires host metabolism, and these changes may be readable in the volatile organic compounds (VOCs) released from the body. Whether whole-body VOC profiles can be mapped onto specific disrupted biochemical pathways has not been tested. In this discovery-phase, single-time-point feasibility study, polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice (14 CLP, 10 sham controls). Whole-body headspace gases were collected 12 h after surgery and analysed by thermal desorption-gas chromatography-mass spectrometry. After preprocessing, 113 features were tested univariately with Benjamini-Hochberg correction and by orthogonal partial least squares discriminant analysis (OPLS-DA). Candidate VOCs (FDR < 0.1, |log2FC| > 0.26, VIP > 1.0) were annotated against PubChem, KEGG COMPOUND, and the Human Metabolome Database. OPLS-DA separated the groups (R2X = 0.489, R2Y = 0.981, Q2 = 0.777; P = 0.001 by 1,000 permutations), and leave-one-out cross-validation classified 95.8% of animals correctly, though n = 24. Of 54 candidate VOCs, 18 had established endogenous origins; 16 fell and 2 rose in septic mice. Pathway mapping indicated four perturbed domains: lipid peroxidation (12 depleted VOCs), ketone body metabolism (3 decreased), cholesterol/isoprenoid metabolism (isoprene, decreased), and putative gut microbiota-associated metabolism (toluene and carbon disulfide, increased). All 18 endogenous VOCs kept candidate status after environment-derived VOCs were removed. Because whole-body headspace volatiles superimpose tissue metabolism, ventilation, activity, and background, these results suggest the septic volatilome may be mapped onto distinct pathway perturbations; ventilation and activity effects cannot be excluded. These findings generate testable hypotheses for non-invasive metabolic phenotyping in sepsis.
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BibTeX
@article{feng2026wholebody,
title = {{Whole-body volatile organic compound profiling reveals metabolic pathway perturbations in a murine polymicrobial sepsis model: a feasibility study.}},
author = {Wan-Yi Feng and Yu Chen and Xiu-Ya Zhang and Rong Fu and Qin Hu and Feng-Feng Mo and Jia-Feng Wang},
journal = {Frontiers in medicine},
year = {2026},
month = oct,
doi = {10.3389/fmed.2026.1978491},
url = {https://europepmc.org/article/MED/42953112},
note = {CC BY},
}
RIS
TY - JOUR
TI - Whole-body volatile organic compound profiling reveals metabolic pathway perturbations in a murine polymicrobial sepsis model: a feasibility study.
AU - Wan-Yi Feng
AU - Yu Chen
AU - Xiu-Ya Zhang
AU - Rong Fu
AU - Qin Hu
AU - Feng-Feng Mo
AU - Jia-Feng Wang
PY - 2026
DA - 2026/10/14
JO - Frontiers in medicine
DO - 10.3389/fmed.2026.1978491
UR - https://europepmc.org/article/MED/42953112
AB - Sepsis rewires host metabolism, and these changes may be readable in the volatile organic compounds (VOCs) released from the body. Whether whole-body VOC profiles can be mapped onto specific disrupted biochemical pathways has not been tested. In this discovery-phase, single-time-point feasibility study, polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice (14 CLP, 10 sham controls). Whole-body headspace gases were collected 12 h after surgery and analysed by thermal desorption-gas chromatography-mass spectrometry. After preprocessing, 113 features were tested univariately with Benjamini-Hochberg correction and by orthogonal partial least squares discriminant analysis (OPLS-DA). Candidate VOCs (FDR < 0.1, |log2FC| > 0.26, VIP > 1.0) were annotated against PubChem, KEGG COMPOUND, and the Human Metabolome Database. OPLS-DA separated the groups (R2X = 0.489, R2Y = 0.981, Q2 = 0.777; P = 0.001 by 1,000 permutations), and leave-one-out cross-validation classified 95.8% of animals correctly, though n = 24. Of 54 candidate VOCs, 18 had established endogenous origins; 16 fell and 2 rose in septic mice. Pathway mapping indicated four perturbed domains: lipid peroxidation (12 depleted VOCs), ketone body metabolism (3 decreased), cholesterol/isoprenoid metabolism (isoprene, decreased), and putative gut microbiota-associated metabolism (toluene and carbon disulfide, increased). All 18 endogenous VOCs kept candidate status after environment-derived VOCs were removed. Because whole-body headspace volatiles superimpose tissue metabolism, ventilation, activity, and background, these results suggest the septic volatilome may be mapped onto distinct pathway perturbations; ventilation and activity effects cannot be excluded. These findings generate testable hypotheses for non-invasive metabolic phenotyping in sepsis.
SN - 2296-858X
ER -