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Shock. 2018 May 8. doi: 10.1097/SHK.0000000000001180. [Epub ahead of print]

Dietary Cellulose Supplementation Modulates the Immune Response in a Murine Endotoxemia Model.

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Department of Critical Care Medicine, University of Pittsburgh School of Medicine.
Department of Pediatrics, University of Pittsburgh School of Medicine.
Department of Critical Care, Children's Hospital of Pittsburgh of UPMC Pittsburgh, PA.
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Department of Immunology, University of Pittsburgh School of Medicine.
Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh of UPMC.


The role of dietary fiber in chronic inflammatory disorders has been explored, but very little is known about its benefits in acute inflammation. Previously, we have demonstrated that dietary cellulose supplementation confers protection in a murine model of sepsis by promoting the growth of the gut microbiota that are linked to metabolic health. The survival benefit is associated with a decrease in serum concentration of pro-inflammatory cytokines, reduced neutrophil infiltration in the lungs, and diminished hepatic inflammation. Here we aim to understand if the benefit of manipulating the gut microbiome exerts a broader "systemic" influence on the immune system in a lethal murine endotoxemia model. We hypothesize that mice fed high fiber cellulose (HF) diet will demonstrate a reduction in activated macrophages and dendritic cells (DCs) and a concomitant increase in the suppressive capacity of T regulatory cells (Tregs) toward T cells responsiveness. We characterized the immunological profile and activation status of macrophages, DCs and T cells in mice on HF diet who were then subjected to endotoxemia. Supplementation with HF diet decreased the number and activation of splenic macrophages and DCs in mice after LPS administration. Similarly, HF diet amplified the suppressive function of Tregs and induced anergy in T cells as compared to mice on a regular diet. Our data suggest that the use of HF diet can be a simple, yet effective tool that decreases the hepatic DNA binding activity of NF-κB leading to a reduction in pro-inflammatory cytokine response in a murine endotoxemia model.

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