Lipopolysaccharide is an important virulence factor of gramnegative bacteria. It is often referred to as endotoxin, which is used synonymously with lipopolysaccharide, although there are a few endotoxins that are not lipopolysaccharides. 1 Virulence is determined as the strength of the pathogenic potential, referring to the relative capacity of a microbe to cause damage in the host and the ability to overcome host defenses. 2 Several virulence factors or characteristics contribute to the ability of a microbe to cause disease. For example, fimbriae, adhesins, and invasins promote colonization, growth, attachment, and invasiveness. Other factors, such as toxins and proteases, are more immunoinhibitory or immunosuppressive and contribute to tissue-destructive capacity and evasion of host responses. Also, the susceptibility of the host plays a role in infections.Lipopolysaccharide resides in the outer membrane of the bacteria, where its hydrophobic structures composed of fatty acid chains anchor the molecule into the bacterial membrane, and the hydrophilic portion (ie the rest of the molecule) projects from the membrane. Lipopolysaccharide is a potent activator of innate and adaptive immune responses, as well as of tissue destruction cascades. It plays a major role in the pathogenesis of periodontitis, where an abundant number of gram-negative species is a typical determinant of the periodontal microbiota.Translocation of lipopolysaccharide to the bloodstream causes endotoxemia (ie, lipopolysaccharide activity present in serum/ plasma). An approximate twofold increase of lipopolysaccharide activity in apparently healthy subjects is considered 'metabolic endotoxemia,' which has been associated with unhealthy nutrition. 3 Circulating endotoxin is alternatively called 'intestinal endotoxemia,' referring to its presumed source, the gastrointestinal tract. The levels reported, for example, among healthy blood donors, middle-aged subjects, or healthy elderly subjects have been 0.3 pg/ml, 1.2 pg/ml, and 6.7 pg/ml, respectively. [4][5][6] The corresponding level may reach 850 pg/ml in gram-negative septic shock caused by lipopolysaccharide. 7 Human cells expressing the lipopolysaccharide receptor complex are highly sensitive and can respond in minutes to picograms per milliliter of lipopolysaccharide. Chronic endotoxemia is involved in the pathogenesis of many inflammation-driven conditions, especially cardiometabolic disorders, including atherosclerotic cardiovascular diseases, obesity, liver diseases, diabetes, and metabolic syndrome,e 8 and thus it is regarded as a risk factor.Periodontitis patients are known to have increased circulating lipopolysaccharide activity and metabolic disturbances, which may be either the cause or effect of endotoxemia. Observations that bacteria disseminate into circulation after toothbrushing and periodontal procedures 9,10 and assumptions that endotoxin may disseminate through inflamed periodontium and bleeding gums support the This is an open access article under the terms of the Creative ...