Antibiotic treatment preventing necrotising enterocolitis alters urinary and plasma metabolomes in preterm pigs

TY - JOUR

T1 - Antibiotic treatment preventing necrotising enterocolitis alters urinary and plasma metabolomes in preterm pigs

AU - Jiang, Pingping

AU - Trimigno, Alessia

AU - Stanstrup, Jan

AU - Khakimov, Bekzod

AU - Viereck, Nanna

AU - Engelsen, Søren Balling

AU - Sangild, Per Torp

AU - Dragsted, Lars Ove

N1 - CURIS 2017 NEXS 245

PY - 2017/10/6

Y1 - 2017/10/6

N2 - Necrotising enterocolitis (NEC) is a serious gut inflammatory condition in premature neonates, onset and development of which depend on the gut microbiome. Attenuation of the gut microbiome by antibiotics can reduce NEC incidence and severity. However, how the antibioticssuppressed gut microbiome affects the whole-body metabolism in NEC-sensitive premature neonates is unknown. In formulafed preterm pigs, used as a model for preterm infants, plasma and urinary metabolomes were investigated by LC-MS and 1H NMR, with and without antibiotic treatment immediately after birth. While it reduced the gut microbiome density and NEC lesions as previously reported, the antibiotic treatment employed in the current study affected the abundance of 44 metabolites in different metabolic pathways. In antibiotics-treated pigs, tryptophan metabolism favored the kynurenine pathway, relative to the serotonin pathway, as shown by specific metabolites. Metabolites associated with the gut microbiome, including 3-phenyllactic acid, 4-hydroxyphenylacetic acid, and phenylacetylglycine, all from phenylalanine, and three bile acids showed lower levels in the antibiotics-treated pigs where the gut microbiome was extensively attenuated. Findings in the current study warrant further investigation of metabolic and developmental consequences of antibiotic treatment in preterm neonates.

AB - Necrotising enterocolitis (NEC) is a serious gut inflammatory condition in premature neonates, onset and development of which depend on the gut microbiome. Attenuation of the gut microbiome by antibiotics can reduce NEC incidence and severity. However, how the antibioticssuppressed gut microbiome affects the whole-body metabolism in NEC-sensitive premature neonates is unknown. In formulafed preterm pigs, used as a model for preterm infants, plasma and urinary metabolomes were investigated by LC-MS and 1H NMR, with and without antibiotic treatment immediately after birth. While it reduced the gut microbiome density and NEC lesions as previously reported, the antibiotic treatment employed in the current study affected the abundance of 44 metabolites in different metabolic pathways. In antibiotics-treated pigs, tryptophan metabolism favored the kynurenine pathway, relative to the serotonin pathway, as shown by specific metabolites. Metabolites associated with the gut microbiome, including 3-phenyllactic acid, 4-hydroxyphenylacetic acid, and phenylacetylglycine, all from phenylalanine, and three bile acids showed lower levels in the antibiotics-treated pigs where the gut microbiome was extensively attenuated. Findings in the current study warrant further investigation of metabolic and developmental consequences of antibiotic treatment in preterm neonates.

KW - Antibiotics

KW - Metabolomics

KW - Necrotising enterocolitis

KW - UPLC-MS

KW - NMR

KW - Preterm pigs

U2 - 10.1021/acs.jproteome.7b00263

DO - 10.1021/acs.jproteome.7b00263

M3 - Journal article

C2 - 28871782

SN - 1535-3893

VL - 16

SP - 3547

EP - 3557

JO - Journal of Proteome Research

JF - Journal of Proteome Research

ER -