Abstract

Faecal lipopolysaccharides (LPS) have attracted attention as potent elements to explain a correlation between the gut microbiota and cardiovascular disease (CVD) progression. However, the underlying mechanism of how specific gut bacteria contribute to faecal LPS levels remains unclear. We retrospectively analysed the data of 92 patients and found that the abundance of the genus Bacteroides was significantly and negatively correlated with faecal LPS levels. The controls showed a higher abundance of Bacteroides than that in the patients with CVD. The endotoxin units of the Bacteroides LPS, as determined by the limulus amoebocyte lysate (LAL) tests, were drastically lower than those of the Escherichia coli LPS; similarly, the Bacteroides LPS induced relatively low levels of pro-inflammatory cytokine production and did not induce sepsis in mice. Fermenting patient faecal samples in a single-batch fermentation system with Bacteroides probiotics led to a significant increase in the Bacteroides abundance, suggesting that the human gut microbiota could be manipulated toward decreasing the faecal LPS levels. In the clinical perspective, Bacteroides decrease faecal LPS levels because of their reduced LAL activity; therefore, increasing Bacteroides abundance might serve as a novel therapeutic approach to prevent CVD via reducing faecal LPS levels and suppressing immune responses.

Highlights

  • Faecal lipopolysaccharides (LPS) have attracted attention as potent elements to explain a correlation between the gut microbiota and cardiovascular disease (CVD) progression

  • The limulus amoebocyte lysate (LAL) tests are the gold standard for measuring LPS levels, it is important to remember that LPS demonstrates its own unique LAL activity due to the structural differences in lipid A moiety,faecal LPS levels measured by the LAL tests do not correctly reflect the absolute mass of L­ PS26

  • We indicated that the abundance of the genus Bacteroides is negatively correlated with the faecal LPS levels measured by the LAL tests

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Summary

Introduction

Faecal lipopolysaccharides (LPS) have attracted attention as potent elements to explain a correlation between the gut microbiota and cardiovascular disease (CVD) progression. Researchers have focused on plasma LPS, and have reported that plasma LPS plays an important role in the process of activating pro-inflammatory cytokines during heart failure, and may be used to predict the development of atherosclerosis and other major advanced cardiac e­ vents[15,16,17]. In this context, Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe 6500017, Japan. We fermented patient faecal samples in the KUHIMM with probiotics to facilitate evaluation of the effect of probiotics on the gut microbiota before clinical studies

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