Abstract
Background
We investigated ‘rare’ bile acids (BA) as potential markers in septic neonates.
Methods
‘Rare’ (C-6 hydroxylated BA) and ‘classical’ BA were determined in 102 neonates using high-performance liquid chromatography—high-resolution mass spectrometry (HPLC-HRMS). Four groups according to maturity (full term, FT vs. preterm, PT) and septic status (early-onset neonatal sepsis, EOS vs. CTR; non-septic controls) were formed: FT-CTR; (n = 47), PT-CTR (n = 22), FT-EOS (n = 20), PT-EOS (n = 13).
Results
Firstly, FT-CTR had a significant higher amount of ‘rare’ BA than PT (FT-CTR: 0.5 µmol/L, IQR: 0.3–1.3 vs. PT-CTR: 0.01 µmol/L, IQR 0.01–0.2; p < 0.01). The most common ‘rare’ BA in FT-CTR were tauro-γ- (TGMCA) and tauro-α-muricholic acid (TAMCA). Secondly, in EOS, absolute ‘rare’ BA levels were comparable in both gestational age groups (FT-EOS: 0.6 µmol/L, IQR: 0.1–1.6 and PT-EOS: 0.6 µmol/L, IQR: 0.2–1.5). Therefore, EOS had significantly higher median ‘rare’ BA values than non-septic PT neonates (p < 0.01). In PT and term neonates, the relative amount of tauro-ω-muricholic acid (TOMCA) within the ‘rare’ BA pool was significantly higher in EOS than in controls (FT-CTR vs. "FT-EOS and PT-CTR vs. PT-EOS; p < 0.01). It was hence the predominant ‘rare’ BA in EOS.
Conclusion
TOMCA is an independent factor associated with EOS. It has diagnostic potential.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Zohrer, E. et al. Serum bile acids in term and preterm neonates: a case-control study determining reference values and the influence of early-onset sepsis. Medicine 95, e5219 (2016).
Tagliacozzi, D. et al. Quantitative analysis of bile acids in human plasma by liquid chromatography-electrospray tandem mass spectrometry: a simple and rapid one-step method. Clin. Chem. Lab. Med. 41, 1633–1641 (2003).
Batta, A. K. et al. Characterization of serum and urinary bile acids in patients with primary biliary cirrhosis by gas-liquid chromatography-mass spectrometry: effect of ursodeoxycholic acid treatment. J. Lipid Res. 30, 1953–1962 (1989).
Shoda, J. et al. Similarity of unusual bile acids in human umbilical cord blood and amniotic fluid from newborns and in sera and urine from adult patients with cholestatic liver diseases. J. Lipid Res. 29, 847–858 (1988).
Nakagawa, M. & Setchell, K. D. Bile acid metabolism in early life: studies of amniotic fluid. J. Lipid Res. 31, 1089–1098 (1990).
Back, P. & Walter, K. Developmental pattern of bile acid metabolism as revealed by bile acid analysis of meconium. Gastroenterology 78, 671–676 (1980).
Stoll, B. J. et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 126, 443–456 (2010).
Simonsen, K. A., Anderson-Berry, A. L., Delair, S. F. & Davies, H. D. Early-onset neonatal sepsis. Clin. Microbiol. Rev. 27, 21–47 (2014).
Koenig, J. M. & Keenan, W. J. Group B streptococcus and early-onset sepsis in the era of maternal prophylaxis. Pediatr. Clin. North. Am. 56, 689–708 (2009).
Stoll, B. J. et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 127, 817–826 (2011).
Srinivasan, L. & Harris, M. C. New technologies for the rapid diagnosis of neonatal sepsis. Curr. Opin. Pediatr. 24, 165–171 (2012).
Hofer, N., Muller, W. & Resch, B. Non-infectious conditions and gestational age influence C-reactive protein values in newborns during the first 3 days of life. Clin. Chem. Lab. Med. 49, 297–302 (2011).
Hornik, C. P. et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum. Dev. 88, S69–S74 (2012).
Amplatz, B. et al. Bile acid preparation and comprehensive analysis by high performance liquid chromatography-high-resolution mass spectrometry. Clin. Chim. Acta 464, 85–92 (2017).
Setchell KD, Schwarz M, O'Connell NC, et al. Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease. J Clin Invest. 1998;102:1690-1703.
Bove KE, Daugherty CC, Tyson W, et al. Bile acid synthetic defects and liver disease. Pediatr Dev Pathol. 2000;3:1-16.19.
Colombo, C., Zuliani, G., Ronchi, M., Breidenstein, J. & Setchell, K. D. Biliary bile acid composition of the human fetus in early gestation. Pediatr. Res. 21, 197–200 (1987).
Jimenez, E. et al. Is meconium from healthy newborns actually sterile? Res. Microbiol. 159, 187–193 (2008).
DiGiulio, D. B. et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS ONE 3, e3056 (2008).
Wahlen, E. & Strandvik, B. Effects of different formula feeds on the developmental pattern of urinary bile acid excretion in infants. J. Pediatr. Gastroenterol. Nutr. 18, 9–19 (1994).
Madan, J. C. et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch. Dis. Child. Fetal Neonatal Ed. 97, F456–F462 (2012).
Scholtens, P. A., Oozeer, R., Martin, R., Amor, K. B. & Knol, J. The early settlers: intestinal microbiology in early life. Annu Rev. Food Sci. Technol. 3, 425–447 (2012).
De Leoz, M. L. et al. Lacto-N-tetraose, fucosylation, and secretor status are highly variable in human milk oligosaccharides from women delivering preterm. J. Proteome Res. 11, 4662–4672 (2012).
Trauner, M., Fickert, P. & Stauber, R. E. Inflammation-induced cholestasis. J. Gastroenterol. Hepatol. 14, 946–959 (1999).
Sacquet, E. C. et al. Bacterial formation of omega-muricholic acid in rats. Appl. Environ. Microbiol. 37, 1127–1131 (1979).
Acknowledgements
The excellent technical assistance of Maria Schäffer is gratefully acknowledged. We thank A.S. Knisely for helpful comments on the manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Zöhrer, E., Meinel, K., Fauler, G. et al. Neonatal sepsis leads to early rise of rare serum bile acid tauro-omega-muricholic acid (TOMCA). Pediatr Res 84, 66–70 (2018). https://doi.org/10.1038/s41390-018-0007-y
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41390-018-0007-y
This article is cited by
-
Elevated total bile acid levels as an independent predictor of mortality in pediatric sepsis
Pediatric Research (2025)
-
High-Throughput Combined Analysis of Saliva Microbiota and Metabolomic Profile in Chinese Periodontitis Patients: A Pilot Study
Inflammation (2024)
-
Metabolic characteristics of plasma bile acids in patients with intrahepatic cholestasis of pregnancy-mass spectrometric study
Metabolomics (2021)


