Lipopolysaccharide and the gut microbiota: considering structural variation

• Published in: FEBS letters Vol. 596; no. 7; pp. 849 - 875
• Main Authors: Mohr, Alex E., Crawford, Meli'sa, Jasbi, Paniz, Fessler, Samantha, Sweazea, Karen L.
• Format: Journal Article
• Language: English
• Published: England 01.04.2022
• Subjects: Animals; Endotoxemia - metabolism; Endotoxins; Gastrointestinal Microbiome; gut barrier; gut microbiome; immunity; Inflammation; lipopolysaccharide binding protein; lipopolysaccharide variant; lipopolysaccharides; Lipopolysaccharides - pharmacology; metabolic endotoxemia; obesity; gut microbiome; lipopolysaccharides; inflammation; lipopolysaccharide variant; immunity; gut barrier; lipopolysaccharide binding protein; obesity; metabolic endotoxemia
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.14328

Systemic inflammation is associated with chronic disease and is purported to be a main pathogenic mechanism underlying metabolic conditions. Microbes harbored in the host gastrointestinal tract release signaling byproducts from their cell wall, such as lipopolysaccharides (LPS), which can act locally and, after crossing the gut barrier and entering circulation, also systemically. Defined as metabolic endotoxemia, elevated concentrations of LPS in circulation are associated with metabolic conditions and chronic disease. As such, measurement of LPS is highly prevalent in animal and human research investigating these states. Indeed, LPS can be a potent stimulant of host immunity, but this response depends on the microbial species’ origin, a parameter often overlooked in both preclinical and clinical investigations. Indeed, the lipid A portion of LPS is mutable and comprises the main virulence and endotoxic component, thus contributing to the structural and functional diversity among LPSs from microbial species. In this review, we discuss how such structural differences in LPS can induce differential immunological responses in the host. Spurring metabolic endotoxemia, lipopolysaccharides from microbes in the gut act locally and systemically by crossing the gut barrier and entering host circulation. Lipopolysaccharides are associated with major chronic diseases and are a prevalent biomarker in animal and human research. However, just as microbes vary, so do their products. Structural differences in LPS can induce differential health responses in the host.