Abstract

In this study, we demonstrated the effects of a high-fiber diet on intestinal lesions, oxidative stress and systemic inflammation in a murine model of endotoxemia. C57BL/6 mice were randomly assigned to four groups: the control group (CONTROL), which received a commercial normal-fiber rodent diet comprising normal fiber; a CLP group, which received a commercial normal-fiber rodent diet and underwent caecal ligation puncture (CLP); a high-fiber group (HFG), which received a commercial high-fiber rodent diet; and a high fiber + CLP group (HFCLP) which received a commercial high-fiber rodent diet and underwent CLP (30%). The sepsis model was created via CLP after 2 weeks of dietary intervention. Notably, dietary high-fiber supplementation in HFCLP group improved survival rates and reduced bacterial loads, compared with CLP alone. In the HFCLP group, dietary fiber supplementation decreased the serum concentrations of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and high-mobility group protein 1 (HMG-1) but raised the concentration of interleukin 10 (IL-10), compared with the levels in CLP mice. Meanwhile, high-fiber supplementation increased the relative proportions of Akkermansia and Lachnospiraceae. These data show that dietary high-fiber supplementation may be therapeutic for sepsis-induced lesions.

Highlights

  • In 2011, more than $20 billion in hospital costs in the United States were attributed to sepsis (Singer et al, 2016), a life-threatening organ pathology caused by a dysregulated host response to infection

  • We demonstrated the effects of a highfiber diet on intestinal lesions, oxidative stress and systemic inflammation in a murine model of endotoxemia

  • This study has demonstrated that dietary supplementation with high fiber alleviates intestinal injuries

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Summary

Introduction

In 2011, more than $20 billion in hospital costs in the United States were attributed to sepsis (Singer et al, 2016), a life-threatening organ pathology caused by a dysregulated host response to infection. During the last 30 years, researchers have investigated a number of unsuccessful immunotherapeutic strategies aimed at circumventing the unregulated pro-inflammatory host response during the initial phases of sepsis. Most of these strategies focused on the cascade of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin (IL)-1 and high-mobility group box 1 (HMGB1), which have all been shown to be of little practical therapeutic value. Morowitz et al (2017) demonstrated that the benefits associated with dietary cellulose intake correlate with enrichment of the gut microbiome taxon Akkermansia, a genus typically associated with improved metabolic health This finding led us to hypothesize that supplementation with cellulose would enhance survival in murine sepsis models by reducing intestinal lesions, modulating oxidative stress and reducing systemic inflammation

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