NEONATAL INTERMITTENT HYPOXIA, FISH OIL AND/OR ANTIOXIDANT SUPPLEMENTATION ON GUT MICROBIOTA IN NEONATAL RATS

BACKGROUND. Preterm infants frequently experience intermittent hypoxia (IH) episodes, rendering them susceptible to oxidative stress and gut dysbiosis. We tested the hypothesis that early supplementation with antioxidants and/or fish oil promotes gut biodiversity and mitigates IH-induced gut injury. METHODS. Newborn rats were exposed to neonatal IH from birth (P0) to P14 during which they received daily oral supplementation with: 1) coenzyme Q10 (CoQ10) in olive oil; 2) fish oil; 3) glutathione nanoparticles (nGSH); 4) CoQ10+fish oil; or 5) olive oil (placebo control). Pups were placed in room air (RA) from P14 to P21 with no further treatment. RA controls were similarly treated. Stool samples were assessed for microbiota and terminal ileum for histopathology and morphometry; total antioxidant capacity; lipid peroxidation; and biomarkers of gut injury. RESULTS. Neonatal IH induced histopathologic changes consistent with necrotizing enterocolitis which were associated with increased lipid peroxidation, toll-like receptor, transforming growth factor, and nuclear factor kappa B. Combination CoQ10+fish oil, and nGSH were most effective for preserving gut integrity, reducing biomarkers of gut injury, and increasing commensal organisms. CONCLUSIONS. Combination antioxidants and fish oil may confer synergistic benefits to mitigate IH-induced injury in the terminal ileum.