Effect of dietary cellulose supplementation on gut barrier function and apoptosis in a murine model of endotoxemia.

Valentina Di Caro,Rajesh K Aneja,Kevin P Mollen,Alicia M Alcamo,Michael J Morowitz,Robert S B Clark,Elizabeth A Novak,Jessica L Cummings,François Blachier

doi:10.1371/journal.pone.0224838

Valentina Di Caro, Rajesh K Aneja + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0224838

Copy DOI

Abstract

The gut plays a vital role in critical illness, and alterations in the gut structure and function have been reported in endotoxemia and sepsis models. Previously, we have demonstrated a novel link between the diet-induced alteration of the gut microbiome with cellulose and improved outcomes in sepsis. As compared to mice receiving basal fiber (BF) diet, mice that were fed a non-fermentable high fiber (HF) diet demonstrated significant improvement in survival and decreased organ injury in both cecal-ligation and puncture (CLP) and endotoxin sepsis models. To understand if the benefit conferred by HF diet extends to the gut structure and function, we hypothesized that HF diet would be associated with a reduction in sepsis-induced gut epithelial loss and permeability in mice. We demonstrate that the use of dietary cellulose decreased LPS-mediated intestinal hyperpermeability and protected the gut from apoptosis. Furthermore, we noted a significant increase in epithelial cell proliferation, as evidenced by an increase in the percentage of bromodeoxyuridine-positive cells in HF fed mice as compared to BF fed mice. Thus, the use of HF diet is a simple and effective tool that confers benefit in a murine model of sepsis, and understanding the intricate relationship between the epithelial barrier, gut microbiota, and diet will open-up additional therapeutic avenues for the treatment of gut dysfunction in critical illness.

Highlights

Under basal conditions, the components of the intestinal microenvironment act in concert to maintain a symbiotic, mutually beneficial relationship [1]
The number of apoptotic cells is comparable in basal fiber (BF) and high fiber (HF) diet mice at 72 h post-LPS administration (Fig 5C). These findings suggest that the use of HF diet in mice is associated with a reduction in LPS-mediated intestinal apoptosis and associated intestinal permeability as compared to mice on BF diet
We have previously demonstrated in two different murine models of sepsis, cecal ligation and puncture (CLP) and endotoxemia, that alterations in the microbiome following high cellulose diet supplementation confers survival protection and reduces the systemic pro-inflammatory response

Summary

Introduction

The components of the intestinal microenvironment (intestinal epithelium, microbiome, and host immune system) act in concert to maintain a symbiotic, mutually beneficial relationship [1]. High fiber reduces LPS-mediated intestine hyperpermeability microbiome, resulting in a loss of microbial diversity, diminution of pro-health commensal microbes, and an increase in the abundance of pathogenic bacteria [3, 4]. The presence of these dominant harmful pathogens within fecal samples has been identified as a risk factor for subsequent infections caused by that same organism [5, 6] and can contribute to metabolic, immune, and neurocognitive disturbances in the critically-ill host [7]. After the onset of sepsis, these disturbed microbial communities can lead to immune exhaustion and a loss of T-helper cells, thereby setting the stage for infections by the dominant pathogens [8]

Methods

Results

Conclusion