['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.', '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.', '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).'] Does lipid Emulsion Formulation of Parenteral Nutrition affect Intestinal Microbiota and Host Responses in Neonatal Piglets?