Introduction: Specialized nutrition support is a common technology applied to surgical and critically ill patients. Currently, there is little understanding of how varying the route of feeding (parenteral versus enteral) and nutritional formulations influence gene expression. We hypothesized that there would exist distinctly different gene expression profiles in monocytes obtained from subjects on enteral versus parenteral routes of feedings. Knowing the effects of nutritional formulation and routes of feeding on gene expression could improve our understanding of the relationship between nutritional substrates, gene expression, and immune and metabolic responses in critically ill patients.

Methods: Nine healthy subjects, aged 18-40, were admitted for 4 days/3 nights. Subjects were randomized into parenteral (TPN, n=6) or enteral (TF, n=3) feeding groups, and all received continuous feedings for 72 hours. All subjects had blood collected for monocyte purification and gene expression analysis by Affymetrix FOCUS chip (8,793 gene probes). Acceptance criteria for differentially expressed genes required >1.5 median fold change (FC) and/or p <0.05. Significant data were annotated to pathways using Ingenuity Pathway Analysis. An innate filter was also applied to the significant gene data set.

Results: Monocytes gene expression after 72 hours of feeding

	All genes	Immune Filter
TF p < 0.05	143 67 up; 76 down	4: 2 up, 2 down
TF p<0.05 + FC > 1.5	11: 4 up; 7 down	1 up
TPN p< 0.05	1524: 1003 up; 521 down	38: 22 up, 16 down
TPN p < 0.05 + FC > 1.5	187: 75 up; 111 down	8: 2 up, 6 down

The above differentially expressed genes were also categorized into immune function pathways. Among the differentially expressed genes in the TPN subjects were up-regulated Signal Transducers and Activators of Transcription (STAT) 1 and 3; up-regulated Toll-Like Receptor 4 (TRL4); up-regulated TNF receptor associated factor 5 (TRAF5); up-regulated gp130 and IL-6 receptor; and down regulated IL-18.

Conclusion: Differing nutritional modalities influence monocyte gene expression. Parenteral feeding appears to have a more profound effect than enteral feeding on monocyte gene expression after 72 hours. By the stringent criteria adopted for this study, the genes and pathways most affected are those involved in immune function and signaling.