Lipid Emulsion Formulation of Parenteral Nutrition Affects Intestinal Microbiota and Host Responses in Neonatal Piglets

Background: Total parenteral nutrition (TPN) is a cause of intestinal microbial dysbiosis and impaired gut barrier function. This may contribute to life-threatening parenteral nutrition–associated liver disease and sepsis in infants. We compared the effects of a lipid emulsion containing long-chain ω-3 polyunsaturated fatty acids (PUFAs; SMOFlipid) and a predominantly ω-6 PUFA emulsion (Intralipid) on microbial composition and host response at the mucosal surface. Materials and Methods: Neonatal piglets were provided isocaloric, isonitrogenous TPN for 14 days versus sow-fed (SF) controls. Equivalent lipid doses (10 g/kg/d) were given of either SMOFlipid (ML; n = 10) or Intralipid (SO; n = 9). Ileal segments and mucosal scrapings were used to characterize microbial composition by 16S rRNA gene sequencing and quantitative gene expression of tight junction proteins, mucins, antimicrobial peptides, and inflammatory cytokines. Results: The microbial composition of TPN piglets differed from SF, while ML and SO differed from each other (analysis of molecular variance; P < .05); ML piglets were more similar to SF, as indicated by UniFrac distance (P < .05). SO piglets showed a specific and dramatic increase in Parabacteroides (P < .05), while ML showed an increase in Enterobacteriaceae (P < .05). Gene expression of mucin, claudin 1, β-defensin 2, and interleukin 8 were higher in TPN; overall increases were significantly less in ML versus SO (P < .05). Conclusion: The formulation of parenteral lipid is associated with differences in the gut microbiota and host response of TPN-fed neonatal piglets. Inclusion of ω-3 long-chain PUFAs appears to improve host-microbial interactions at the mucosal surface, although mechanisms are yet to be defined.