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. 2020 Aug 13;10(8):331.
doi: 10.3390/metabo10080331.

Antibiotics Effects on the Fecal Metabolome in Preterm Infants

Laura Patton  1 , Nan Li  1 , Timothy J Garrett  2 , J Lauren Ruoss  1 , Jordan T Russell  3 , Diomel de la Cruz  1 , Catalina Bazacliu  1 , Richard A Polin  4 , Eric W Triplett  3 , Josef Neu  1
Affiliations

Antibiotics Effects on the Fecal Metabolome in Preterm Infants

Laura Patton et al. Metabolites. .

Abstract

Within a randomized prospective pilot study of preterm infants born at less than 33 weeks' gestation, weekly fecal samples from 19 infants were collected and metabolomic analysis was performed. The objective was to evaluate for differences in fecal metabolites in infants exposed to antibiotics vs. not exposed to antibiotics in the first 48 h after birth. Metabolomics analysis was performed on 123 stool samples. Significant differences were seen in the antibiotics vs. no antibiotics groups, including pathways related to vitamin biosynthesis, bile acids, amino acid metabolism, and neurotransmitters. Early antibiotic exposure in preterm infants may alter metabolites in the intestinal tract of preterm infants. Broader multi-omic studies that address mechanisms will guide more prudent antibiotic use in this population.

Keywords: antibiotics; metabolome; preterm infants.

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Conflict of interest statement

Josef Neu is the principal investigator of a study with Infant Bacterial Therapeutics and on the Scientific Advisory Boards of Medela and Astarte. No other authors have conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Comparison of Groups A, C1 and C2. (A) PLS–DA plot depicting overlapping components of groups A (red), C1 (green) and C2 (blue). (B) 3D plot showing further delineation of groups C1 (red) and C2 (green).
Figure 2
Figure 2
Volcano plot. Illustrates the scatter of metabolites with increased significance at the extremes of the plot.
Figure 3
Figure 3
Heat map. Color gradients depicting increased (red) versus decreased (blue) concentrations. (A) Top 25 negative ion metabolites (p < 0.05). (B) Top 25 positive ion metabolites (p < 0.05).
Figure 4
Figure 4
Concentrations compared between groups C1 and C2. (A) Primary bile acid, cholate, with unchanged level despite antibiotic administration (p > 0.05). (B,C) Conjugated bile acids taurocholic acid and glycocholic acid. Both with increased expression in the group given antibiotics (p = 0.043 for taurocholic acid, p = 0.047 for glycocholic acid).
Figure 5
Figure 5
Neurotransmitters. Fecal concentrations compared between groups C1 and C2. (A–D) Neurotransmitters falling within the serotonin pathway: tryptophan (p = 0.047), 5-HT (p = 0.17), serotonin (p = 0.82), dopamine (p = 0.40). (E) GABA (p = 0.001), a neurotransmitter which is produced in high quantities within enterocytes.
Figure 6
Figure 6
Amino Acids. Fecal concentrations compared between groups C1 and C2. (A) Glutamine, with a trend of decreased concentration in the group exposed to antibiotics (p > 0.05). (B) Ornithine, with increased concentration in the group exposed to antibiotics (p = 0.001).
Figure 7
Figure 7
Concentrations compared between groups C1 and C2. Shikimate, bacterial metabolite important within the shikimate-folate pathway (p = 0.043).
Figure 8
Figure 8
Study Collection Timeline.
Figure 9
Figure 9
Group schematic. * Represents the total after 3 were bailed from Group C2.
See this image and copyright information in PMC

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