Fecal Microbiota Transplantation Protects the Intestinal Mucosal Barrier by Reconstructing the Gut Microbiota in a Murine Model of Sepsis.

Xiaowei Gai,Haotian Zhao,Cong He,Heling Zhao,Yaqing Li,Huawei Wang,Zihui Wang

doi:10.3389/fcimb.2021.736204

Abstract

The gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies have shown that the gut flora was significantly altered in critically ill patients. This study aimed to observe what kind of GM dysbiosis is in the early stage of sepsis and whether the application of fecal microbiota transplantation (FMT) can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. The study investigated the effect of FMT on gut microbiota, mucosal barrier function, inflammatory response, and survival in a murine model of sepsis established by cecal ligation and puncture (CLP). It is found that FMT can not only reduce morbidity and mortality and restore the abundance and diversity of the gut flora in septic mice, but can also improve the intestinal barrier function by reducing epithelial cell apoptosis, improving the composition of the mucus layer, upregulating the expression of tight junction proteins, and reducing intestinal permeability and the inflammatory response. After FMT, Lachnospiraceae contributed the most to intestinal protection through enhancement of the L-lysine fermentation pathway. FMT offers a microbe-mediated survival advantage in a murine model of sepsis. Therefore, an improved understanding of the connection between microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis.

Highlights

Sepsis continues to be the leading cause of mortality in the intensive care unit (Fay et al, 2017; Haak and Wiersinga, 2017)
Studies have shown that the microbial diversity is diminished within 6 hours of admission to the intensive care unit, and this lack of diversity has been associated with poor outcomes in critically ill patients (Fay et al, 2019)
The results of the western blot showed that the expression of caspase 3 in the cecal ligation and puncture (CLP) group at 24 and 48 h was higher than that in the fecal microbiota transplantation (FMT) group, P < 0.001 (Figure 1C)

Summary

Introduction

Sepsis continues to be the leading cause of mortality in the intensive care unit (Fay et al, 2017; Haak and Wiersinga, 2017). Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection (Ames et al, 2018; Fay et al, 2019; Gong et al, 2019). The host provides an important habitat and nutrients for the microbiome, and the gut microbiota supports the development of the metabolic system and the maturation of the intestinal immune system by providing beneficial nutrients, for example, by the synthesis of vitamins and short-chain fatty acids (SCFAs) (Shi et al, 2017). Studies have shown that the microbial diversity is diminished within 6 hours of admission to the intensive care unit, and this lack of diversity has been associated with poor outcomes in critically ill patients (Fay et al, 2019)

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Conclusion