Metabolic footprint of sepsis and septic shock: A narrative review

Table 1 Platforms used in metabolomics studies of sepsis and septic shock

Analytical platform	Metabolite coverage	Major advantages	Key limitations	Relevance in sepsis research
¹H nuclear magnetic resonance	Organic acids, amino acids, sugars, selected lipids	High reproducibility; minimal sample preparation; quantitative; non-destructive	Lower sensitivity; limited detection of low- prevalence metabolites	Metabolic pattern recognition, disease stratification, longitudinal monitoring
Gas chromatography-mass spectrometry	Volatile and derivatized metabolites, organic acids, short-chain fatty acids	Excellent chromatographic resolution; robust compound identification	Derivatization required; limited to volatile/semi-volatile compounds	Assessment of microbial-derived metabolites and energy metabolism
Liquid chromatography-mass spectrometry	Lipids, acylcarnitines, amino acids, bile acids, microbial metabolites	High sensitivity; broad metabolite coverage; targeted and untargeted analysis	Ion suppression; batch effects; requires rigorous standardization	Biomarker discovery, prognostic modeling, metabolic phenotyping

Table 2 Clinical metabolomics studies in sepsis and septic shock

Ref.	Clinical context	Analytical platform	Key metabolic pathways	Main clinical insight
Pandey et al[39] (2023)	Treatment response in septic shock	¹H NMR	Ketone bodies, amino acids, choline metabolism	Responsive patients- higher choline and glutamate. Lactate, 3 Hydroxybutyrate, and phenylalanine were lower
Li et al[40] (2023)	Sepsis vs healthy controls	LC-MS/MS	Phenylalanine and tryptophan metabolism	Identified novel aromatic metabolites linked to sepsis
Feng et al[41] (2022)	Trauma (non-SIRS) vs sepsis	LC-MS/MS	Nucleotide and lipid metabolism	Nine discriminatory metabolites identified that predicted septic conversion
Chen et al[42] (2022)	Sepsis vs healthy control	LC-MS/MS	Multi-pathway disruption	Broad metabolite panel (73 metabolites) predicting sepsis onset
Pandey et al[43] (2021)	Septic shock profiling	¹H NMR	Energy metabolism, ketone bodies	Distinct metabolic markers that upregulated vs those that down regulated in septic shock
Jaurila et al[44] (2020)	Sepsis mortality	¹H NMR	Central carbon metabolism	Elevated lactate and citrate linked to mortality
Chung et al[45] (2019)	Septic shock prognosis	UHPLC-MS	Carnitine metabolism	High acetylcarnitine associated with non survival
Huang et al[46] (2019)	Severe infection risk stratification	LC-MS/MS	Amino acid catabolism	Phenylalanine and leucine predicted outcome and prognostication for severe infections
Cambiaghi et al[47] (2018)	Septic shock lipidomics	LC-MS/MS	Phospholipid remodelling	Lipidome alterations linked to mortality
Liu et al[48] (2019)	Septic shock prognosis	LC-MS/MS	BCAA and carnitine pathways	Metabolites (43 key metabolites and 6 Primary discriminators) discriminated survivors
Neugebauer et al[49] (2016)	Sepsis vs SIRS	LC-MS/MS	Lipid remodelling	Distinct lipid markers (Acylcarnitines, glycerophospholipids and sphingolipids) separated sepsis from SIRS
Langley et al[38] (2013)	Sepsis survivor vs non-survivor vs non infected SIRS	LC-MS/MS	Mitochondrial and nucleotide metabolism	Distinct survivor vs non-survivor metabolic profile
Schmerler et al[37] (2012)	Sepsis vs noninfectious SIRS	LC-MS/MS	Lipid metabolism (acylcarnitines and glycerophospholipids)	Acylcarnitine and glycerophospholipid significantly differed between sepsis and SIRS
Stringer et al[36] (2011)	Sepsis-induced ALI	¹H NMR	Oxidative stress and apoptosis	Metabolites reflected lung injury mechanisms
Cohen et al[35] (2010)	Trauma-related septic shock	¹H NMR	Lipid and glucose metabolism	Non-survivors showed lipid accumulation
Mao et al[34] (2009)	Trauma with SIRS or MODS	¹H NMR	Energy and lipid metabolism	Distinct metabolic profiles in MODS vs SIRS

UHPLC-MS: Ultra-high performance liquid chromatography-mass spectrometry; LC-MS: Liquid chromatography-mass spectrometry; MS: Mass spectrometry; BCAA: Branched chained amino acids; ALI: Acute lung injury; NMR: Nuclear magnetic resonance; MODS: Multiple organ dysfunction syndrome; SIRS: Systemic inflammatory response syndrome.