Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk.
Compelling evidence supports the concepts that gut microbiota actively promotes weight gain and fat accumulation and sustains, indirectly, a condition of low-grade inflammation, thus enhancing the cardiovascular risk. Fewer Bacteroidetes and more Firmicutes seem to characterize the gut microbiota of obese people as compared with that of lean individuals. This difference translates into an increased efficiency of microbiota of obese individuals in harvesting energy from otherwise indigestible carbohydrates. Furthermore, the microbiota also seems able to favor fat accumulation. Indeed, studies performed in germ-free animals have demonstrated that conventionalization of sterile intestine with gut microbiota is associated with an enhanced expression of various lipogenic genes in different tissues, i.e., hepatic, adipose, and muscle tissues. Finally, the microbiota favors systemic exposure to the lipopolysaccharides (LPSs), large glycolipids derived from the outer membrane of Gram-negative bacteria. LPSs can cause a condition of "metabolic endotoxemia" characterized by low-grade inflammation, insulin resistance, and augmented cardiovascular risk. LPSs are a powerful trigger for the innate immune system response. Upon binding to the Toll-like receptor 4 and its coreceptors, LPSs trigger a cascade of responses ultimately resulting in the release of proinflammatory molecules that interfere with modulation of glucose and insulin metabolism, promote development and rupture of the atherosclerotic plaque, and favor progression of fatty liver disease to steatohepatitis. This review gives a comprehensive breakdown of the interaction among gut microbiota, LPSs, and the innate immune system in the development of obesity and promotion of an individual's cardiovascular risk.
Manco
Melania
M
Bambino Gesù Hospital, Instituto di Ricovero e Cura a Carattere Scientifico, Piazza San Onofrio 4, I-00165 Rome, Italy. melaniamanco@tiscali.it
Putignani
Lorenza
L
Bottazzo
Gian Franco
GF
D002318:Cardiovascular Diseases / Q000276:immunology* / Q000382:microbiology*; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D009765:Obesity / Q000276:immunology* / Q000382:microbiology*
D008070:Lipopolysaccharides