Lipidomic analysis of patients with microbial invasion of the amniotic cavity reveals up-regulation of leukotriene B4.
Bioactive lipids derived from the metabolism of polyunsaturated fatty acids are important mediators of the inflammatory response. Labor per se is considered a sterile inflammatory process. Intra-amniotic inflammation (IAI) due to microorganisms (i.e., intra-amniotic infection) or danger signals (i.e., sterile IAI) has been implicated in the pathogenesis of preterm labor and clinical chorioamnionitis at term. Early and accurate diagnosis of microbial invasion of the amniotic cavity (MIAC) requires analysis of amniotic fluid (AF). It is possible that IAI caused by microorganisms is associated with a stereotypic lipidomic profile, and that analysis of AF may help in the identification of patients with this condition. To test this hypothesis, we analyzed the fatty acyl lipidome of AF by liquid chromatography-mass spectrometry from patients in spontaneous labor at term and preterm gestations. We report that the AF concentrations of proinflammatory lipid mediators of the 5-lipoxygenase pathway are significantly higher in MIAC than in cases of sterile IAI. These results suggest that the concentrations of 5-lipoxygenase metabolites of arachidonic acid, 5-hydroxyeicosatetraenoic acid, and leukotriene B4in particular could serve as potential biomarkers of MIAC. This finding could have important implications for the rapid identification of patients who may benefit from anti-microbial treatment.-Maddipati, K. R., Romero, R., Chaiworapongsa ,T., Chaemsaithong, P., Zhou, S.-L., Xu, Z., Tarca, A. L., Kusanovic, J. P., Gomez, R., Chaiyasit, N., Honn, K. V. Lipidomic analysis of patients with microbial invasion of the amniotic cavity reveals up-regulation of leukotriene B4.
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA; Lipidomics Core Facility, Wayne State University School of Medicine, Detroit, Michigan, USA; maddipati@wayne.edu.
Krishna Rao
KR
Maddipati
Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, USA.
Roberto
R
Romero
Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Tinnakorn
T
Chaiworapongsa
Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Piya
P
Chaemsaithong
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA; Lipidomics Core Facility, Wayne State University School of Medicine, Detroit, Michigan, USA.
Sen-Lin
SL
Zhou
Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Zhonghui
Z
Xu
Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA; Department of Computer Science, Wayne State University, Detroit, Michigan, USA.
Adi L
AL
Tarca
Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; Center for Research and Innovation in Maternal-Fetal Medicine (CIMAF), Department of Obstetrics and Gynecology, Sótero del Río Hospital, Santiago, Chile Division of Obstetrics and Gynecology, Pontificia Universidad Católica de Chile, Santiago, Chile; and.
Juan Pedro
JP
Kusanovic
Division of Obstetrics and Gynecology, Pontificia Universidad Católica de Chile, Santiago, Chile; and Center for Perinatal Diagnosis (CEDIP), Research and Academic Innovations, Hospital Clínico La Florida, Santiago, Chile.
Ricardo
R
Gomez
Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Noppadol
N
Chaiyasit
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Kenneth V
KV
Honn
D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism* / Q000382:microbiology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005865:Gestational Age; D006801:Humans; D007743:Labor, Obstetric / Q000502:physiology*; D007975:Leukotriene B4 / Q000378:metabolism*; D007752:Obstetric Labor, Premature / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000378:metabolism*; D047929:Term Birth / Q000502:physiology*; D015854:Up-Regulation
D015415:Biomarkers; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase
 infection; 5-lipoxygenase; amniotic fluid; clinical chorioamnionitis; inflammation