Enteral High Fat-Polyunsaturated Fatty Acid Blend Alters the Pathogen Composition of the Intestinal Microbiome in Premature Infants with an Enterostomy

Abstract

Objective: To determine the effect of enteral fish oil and safflower oil supplementation on the intestinal microbiome in infants with an enterostomy born premature.

Study design: Infants with an enterostomy born premature were randomized to receive early enteral supplementation with a high-fat polyunsaturated fatty acid (HF-PUFA) blend of fish oil and safflower oil vs standard nutritional therapy. We used 16S rRNA gene sequencing for longitudinal profiling of the microbiome from the time of study entry until bowel reanastomosis. We used weighted gene coexpression network analysis to identify microbial community modules that differed between study groups over time. We performed imputed metagenomic analysis to determine metabolic pathways associated with the microbial genes.

Results: Sixteen infants were randomized to receive enteral HF-PUFA supplementation, and 16 infants received standard care. The intestinal microbiota of infants in the treatment group differed from those in the control group, with greater bacterial diversity and lower abundance of Streptococcus, Clostridium, and many pathogenic genera within the Enterobacteriaceae family. We identified 4 microbial community modules with significant differences between groups over time. Imputed metagenomic analysis of the microbial genes revealed metabolic pathways that differed between groups, including metabolism of amino acids, carbohydrates, fatty acids, and secondary bile acid synthesis.

Conclusion: Enteral HF-PUFA supplementation was associated with decreased abundance of pathogenic bacteria, greater bacterial diversity, and shifts in the potential metabolic functions of intestinal microbiota.

Trial registration: ClinicalTrials.gov:NCT01306838.

Keywords: microbiota; neonate; nutrition.

Conflict of interest statement

The authors declare no conflicts of interest.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Figure 2

Changes in the relative proportion of the 15 most abundant bacteria genera over time in control and treatment groups.

Figure 5

Weighted gene co-expression network analysis identified 10 unique bacterial community modules. A. The relative abundance of network modules in treatment and control group infants over time. B. Venn diagram showing overlap of genera within the four modules with significant differences between treatment and control groups. Many genera were represented in more than one module, and some were unique to a specific module. C. The composition of four modules with significant differences between treatment groups. The number of unique OTUs, unique families, and unique genera within each module are noted, followed by a list of three genera enriched in each module.

Figure 8

Metabolic pathways associated with microbial genes. A. The relative proportion of metabolic pathways with significant differences between treatment and control groups over time. B. KEGG metabolic pathways that differed between treatment and control groups. Shaded boxes represent the time interval with significant differences between groups by SS-ANOVA. Purple shading indicates pathways with greater abundance in the control group and green represents pathways with greater abundance in the treatment group. Darker shading indicates a greater magnitude of difference between groups.