title: Human meconium contains significant amounts of alkaline sphingomyelinase, neutral ceramidase, and sphingolipid metabolites.
abstract: Intestinal alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase may catalyze the hydrolysis of endogenous sphingomyelin (SM) and milk SM in human-milk fed infants. The enzymes generate sphingolipid metabolites that may influence gut maturation. Alk-SMase also inactivates platelet-activating factor (PAF) that is involved in the pathogenesis of necrotizing enterocolitis (NEC). We examined whether the two enzymes are expressed in both preterm and term infants and analyzed Alk-SMase, neutral ceramidase, SM, and sphingolipid metabolites in meconium. Meconium was collected from 46 preterm (gestational ages 23-36 wk) and 38 term infants (gestational ages 37-42 wk) and analyzed for Alk-SMase using C-choline-labeled SM and for neutral ceramidase using C-octanoyl-sphingosine as substrates. Molecular species of SM, ceramide, and sphingosine were analyzed by high-performance liquid chromatography mass spectroscopy. Meconium contained significant levels of Alk-SMase and ceramidase at all gestational ages. It also contained 16-24 carbon molecular species of SM, palmitoyl- and stearoyl-sphingosine, and sphingosine. There were positive correlations between levels of SM and ceramide and between ceramide and sphingosine levels. In conclusion, Alk-SMase and ceramidase are expressed in the gut of both preterm and term newborn infants and may generate bioactive sphingolipid messengers.
authors.affiliation: Department of Clinical Sciences, Medicine (Gastroenterology and Nutrition), Lund University Hospital, Lund, Sweden.
authors.forename: Rui-Dong
authors.initials: RD
authors.lastname: Duan
authors.forename: Yajun
authors.initials: Y
authors.lastname: Cheng
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
authors.forename: Lena
authors.initials: L
authors.lastname: Ohlsson
authors.forename: Andreas
authors.initials: A
authors.lastname: Herbst
authors.forename: Lena
authors.initials: L
authors.lastname: Hellström-Westas
authors.forename: Ake
authors.initials: A
authors.lastname: Nilsson
mesh_terms: D000581:Amidohydrolases / Q000502:physiology*; D055572:Ceramidases; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D008470:Meconium / Q000201:enzymology*; D055576:Neutral Ceramidase; D013107:Sphingolipids / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000502:physiology*
chemical_list: D013107:Sphingolipids; D013108:Sphingomyelin Phosphodiesterase; D000581:Amidohydrolases; C526744:ASAH2 protein, human; D055572:Ceramidases; D055576:Neutral Ceramidase