Association of Cesarean Delivery and Formula Supplementation with the Stool Metabolome of 6-Week-Old Infants.

Anne G Hoen,Modupe O Coker,Margaret R Karagas,Wimal Pathmasiri,Juliette C Madan,Erika F Dade,Susan Sumner,Susan Mcritchie,Brett T Doherty

doi:10.3390/metabo11100702

Abstract

Cesarean delivery and formula feeding have both been implicated as important factors associated with perturbations to the infant gut microbiome. To investigate the functional metabolic response of the infant gut microbial milieu to these factors, we profiled the stool metabolomes of 121 infants from a US pregnancy cohort study at approximately 6 weeks of life and evaluated associations with delivery mode and feeding method. Multivariate analysis of six-week stool metabolomic profiles indicated discrimination by both delivery mode and diet. For diet, exclusively breast-fed infants exhibited metabolomic profiles that were distinct from both exclusively formula-fed and combination-fed infants, which were relatively more similar to each other in metabolomic profile. We also identified individual metabolites that were important for differentiating delivery mode groups and feeding groups and metabolic pathways related to delivery mode and feeding type. We conclude based on previous work and this current study that the microbial communities colonizing the gastrointestinal tracts of infants are not only taxonomically, but also functionally distinct when compared according to delivery mode and feeding groups. Further, different sets of metabolites and metabolic pathways define delivery mode and diet metabotypes.

Highlights

Diverse microbial communities colonize the intestinal tracts of newborns within hours to days of life [1], serving their host with critical physiological functions including nutrient and drug metabolism, immune maturation, and regulation of inflammatory processes [2,3,4,5,6,7,8,9]
The early life exposures governing the initial assembly of the gut-associated microbiota in infancy have been recently examined using both 16S rRNA gene and shotgun metagenomic sequencing methods, and it is well established that two important factors shaping the composition and genomic makeup of the infant gut microbiome are delivery mode and feeding pattern [10,11,12,13,14,15,16]
We evaluated associations between stool metabolomics profiles and both delivery mode and feeding method in 6-week-old infants enrolled in the New Hampshire Birth Cohort Study (NHBCS)

Summary

Introduction

Diverse microbial communities colonize the intestinal tracts of newborns within hours to days of life [1], serving their host with critical physiological functions including nutrient and drug metabolism, immune maturation, and regulation of inflammatory processes [2,3,4,5,6,7,8,9]. The early life exposures governing the initial assembly of the gut-associated microbiota in infancy have been recently examined using both 16S rRNA gene and shotgun metagenomic sequencing methods, and it is well established that two important factors shaping the composition and genomic makeup of the infant gut microbiome are delivery mode (vaginal vs Cesarean section delivery) and feeding pattern (breast milk vs formula feeding) [10,11,12,13,14,15,16]. Metabolomics provides a physiologically meaningful and powerful signal of the microbiome’s functional activity or phenotype; the normal infant fecal metabolome and any consequences of delivery mode and early feeding patterns on its development have not been described

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Methods

Results