734

Abstract

Introduction: Sepsis and septic shock syndrome are one of the leading causes of death in critically ill patients. Lipopolysaccharide (LPS) released by bacteria within the colon can translocate across a compromised lumen, leading to oxidative stress, inflammation, sepsis and eventually death. Traditional enteral feeds are casein based which are thought to be proteo-toxic and can exacerbate these issues. We hypothesized that an enteral formula based on whey-proteins and that are high in cysteine (antioxidant precursor), and the addition of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and prebiotic fructooligosaccharides (FOS) are protective against LPS induced sepsis in a mouse model. Methods: Mice were fed (1) whey peptide based diet with high protein and EPA-DHA (PAF), (2) whey peptide based diet without EPA-DHA (PSTD), or casein based control diet (CONT). Results: We found that mice fed PAF or PSTD were protected against LPS induced weight loss. Whey-based diets suppressed inflammatory cytokine release such as IL-6, TNFα, and IFNγ. Furthermore, whey-based diets were able to limit oxidative stress damage. PAF and PSTD were able to inhibit autophagy, a mechanism in which the cell recycles damaged organelles suggesting less cellular damage. We believe these effects are likely due to whey-proteins ability to activate mTOR a negative regulator for autophagy. These anti-inflammatory and anti-oxidative effects of PSTD and PAF resulted in decreased liver inflammation and intestinal damage and promoted protective microflora within the intestines. Conclusions: Taken together, these data suggest a clinical role for whey-protein based diets in promoting healing and recovery in the critically ill.