Like Cures Like: Pharmacological Activity of Anti-Inflammatory Lipopolysaccharides From Gut Microbiome

Abstract

Gut microbiome maintains local gut integrity and systemic host homeostasis, where optimal control of intestinal lipopolysaccharides (LPS) activity may play an important role. LPS mainly produced from gut microbiota are a group of lipid-polysaccharide chemical complexes existing in the outer membrane of Gram-negative bacteria. Traditionally, LPS mostly produced from Proteobacteria are well known for their ability in inducing strong inflammatory responses (proinflammatory LPS, abbreviated as P-LPS), leading to septic shock or even death in animals and humans. Although the basic structures and chemical properties of P-LPS derived from different bacterial species generally show similarity, subtle and differential immune activation activities are observed. On the other hand, frequently ignored, a group of LPS molecules mainly produced by certain microbiota bacteria such as Bacteroidetes show blunt or even antagonistic activity in initiating pro-inflammatory responses (anti-inflammatory LPS, abbreviated as A-LPS). In this review, besides the immune activation properties of P-LPS, we also focus on the description of anti-inflammatory effects of A-LPS, and their potential antagonistic mechanism. We address the possibility of using native or engineered A-LPS for immune modulation in prevention or even treatment of P-LPS induced chronic inflammation related diseases. Understanding the exquisite interactive relationship between structure-activity correlation of P- and A-LPS not only contributes to molecular understanding of immunomodulation and homeostasis, but also re-animates the development of novel LPS-based pharmacological strategy for prevention and therapy of chronic inflammation related diseases.