Discrimination of sepsis stage metabolic profiles with an LC/MS-MS-based metabolomics approach

Su, Longxiang; Huang, Yu; Zhu, Ying; Xia, Lei; Wang, Ren-Tao; Xiao, Kun; Wang, Huijuan; Peng, Yan; Wen, Bo; Cao, Lichao; Meng, Nan; Luan, Hemi; Liu, Changting; Li, Xin; Xie, Lixin

doi:10.1136/bmjresp-2014-000056

Cited by 55 publications

(58 citation statements)

References 34 publications

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“…Further analysis revealed that 2-phenylacetamide, dimethyllysine, glyceryl-phosphoryl-ethanolamine and D-cysteine could predict the severity of sepsis. Glyceryl-phosphoryl-ethanolamine is necessary for anticoagulation activity, and its altered expression level could be due to coagulation disorders and vascular endothelial dysfunction during severe sepsis 71 . It is necessary to validate these results in additional cohorts to determine their clinical utility.…”

Section: Metabolomicsmentioning

confidence: 99%

Mass spectrometry for the discovery of biomarkers of sepsis

Ludwig

Hummon

2017

Mol. BioSyst.

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Sepsis is a serious medical condition that occurs in 30% of patients in intensive care units (ICUs). Early detection of sepsis is key to prevent its progression to severe sepsis and septic shock, which can cause organ failure and death. Diagnostic criteria for sepsis are nonspecific and hinder a timely diagnosis in patients. Therefore, there is currently a large effort to detect biomarkers that can aid physicians in the diagnosis and prognosis of sepsis. Mass spectrometry is often the method of choice to detect metabolomic and proteomic changes that occur during sepsis progression. These “omics” strategies allow for untargeted profiling of thousands of metabolites and proteins from human biological samples obtained from septic patients. Differential expression of or modifications to these metabolites and proteins can provide a more reliable source of diagnostic biomarkers for sepsis. Here, we focus on the current knowledge of biomarkers of sepsis and discuss the various mass spectrometric technologies used in their detection. We consider studies of the metabolome and proteome and summarize information regarding potential biomarkers in both general and neonatal sepsis.

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Section: Metabolomicsmentioning

confidence: 99%

Mass spectrometry for the discovery of biomarkers of sepsis

Ludwig

Hummon

2017

Mol. BioSyst.

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“…There is relatively little metabolomics work in sepsis, but in one study, carnitine and sphingolipid metabolism were also modified during sepsis (1013), while in another (1014), a suite of molecules were decreased during acute sepsis. However, the patients involved here were quite close to death, so it is not clear that comparisons between the metabolome in PE and in dying patients are that worthwhile.…”

Section: Metabolomic Biomarkersmentioning

confidence: 99%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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“…There is relatively little metabolomics work in sepsis, but in one study carnitine and sphingolipid metabolism were also modified during sepsis [946], while in another [947] a suite of molecules were decreased during acute sepsis. However, the patients involved here were quite close to death, so it is not clear that comparisons between the metabolome in PE and in dying patients are that worthwhile.…”

Section: Metabolomic Biomarkersmentioning

confidence: 99%

A Dormant Microbial Component in the Development of Pre-Eclampsia¹

Kell

Kenny

2016

Preprint

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Pre-eclampsia (PE) is a complex, multi-system disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE, and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused.We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is in fact microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “pre-eclampsia” that we assessed has in fact also been shown to be raised in response to infection. An infectious component to PE fulfils the Bradford Hill criteria for ascribing a disease to an environmental cause, and suggests a number of treatments, some of which have in fact been shown to be successful.PE was classically referred to as endotoxaemia or toxaemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the aetiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.Insight, innovation, integrationMany descriptors of pre-eclampsia are widely accepted (e.g. abnormal trophoblast invasion, oxidative stress, inflammation and altered immune response, and anti-angiogenic responses). However, without knowing what causes them, they do not explain the syndrome. The Biological Insight of this manuscript is that there is considerable evidence to the effect that each of these phenomena (hence PE) are caused by the resuscitation of dormant bacteria that shed (known and potent) inflammagens such as LPS, often as a consequence of iron availability. PE is thus seen as a milder form of sepsis. The Technological Innovations come from the use of molecular markers (of microbes and omics more generally, as well as novel markers of coagulopathies) to measure this. The Benefit of Integration comes from bringing together a huge number of disparate observations into a unifying theme.

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Discrimination of sepsis stage metabolic profiles with an LC/MS-MS-based metabolomics approach

Cited by 55 publications

References 34 publications

Mass spectrometry for the discovery of biomarkers of sepsis

Mass spectrometry for the discovery of biomarkers of sepsis

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Pre-Eclampsia¹

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Discrimination of sepsis stage metabolic profiles with an LC/MS-MS-based metabolomics approach

Cited by 55 publications

References 34 publications

Mass spectrometry for the discovery of biomarkers of sepsis

Mass spectrometry for the discovery of biomarkers of sepsis

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Pre-Eclampsia1

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A Dormant Microbial Component in the Development of Pre-Eclampsia¹