Introduction: Pediatric Acute Respiratory Distress Syndrome (PARDS) is a life-threatening condition with mortality of up to 33%. Retrospective studies suggest early enteral nutrition (EEN) may reduce PARDS mortality, though mechanisms are unclear. We hypothesize that diet-driven modulation of the gut microbiome is a potential mechanism for EEN effects on PARDS outcomes.
Methods: Subgroup analysis of a pilot randomized controlled trial of EEN+/- PN in PARDS, to compare patients who received fructo-oligosaccharide (FOS)-containing EEN (EEN+FOS) with those who did not (EEN-FOS). Eighteen patients were enrolled; both groups received equivalent protein, and calories to deliver basal metabolic rate. Outcomes included measures of gut microbial diversity, relative abundance of butyrate-producing gut bacteria, plasma and urine biomarkers of gut integrity and permeability, and systemic inflammatory cytokines. Microbiota composition was assessed via 16S rRNA gene sequencing using MiSeq Illumina, followed by bioinformatic analysis with MacQiime v1.9.1 and R. Statistics: Wilcoxon rank-sum.
Results: EN+FOS was associated with greater gut species richness and beta diversity, which was comparable to healthy controls, unlike the EN-FOS group. EN+FOS was associated with increased relative abundance at the genus level of butyrate-producing Faecalibacterium and Subdoligranulum. Plasma Intestinal Fatty Acid Binding Protein (iFABP), a biomarker of intestinal epithelial cell integrity, was significantly lower in patients with EN+FOS (p=0.003), indicating improved intestinal epithelial integrity. Urine Lactulose/Mannitol Ratios were lower for patients with EN+FOS, p=0.02, indicating a less permeable intestinal epithelium. Plasma TNF-α and IL-6 levels did not differ significantly between groups (p=0.6 and p=0.07, respectively). Mean fecal butyrate concentrations were 56.5 mg/100gm and 5.2 mg/100gm, for EN+FOS and EN-FOS, respectively, but was not significant (p=0.07).
Conclusions: Although limited by small sample size, this subgroup analysis suggests that FOS supplementation of EEN may preserve gut microbiome diversity and improve intestinal barrier integrity in PARDS. Further study is needed to determine if FOS supplementation can act via butyrate signaling to improve lung inflammation, and ultimately, improve PARDS outcomes.
