Milan K Piya1, Alison L Harte, Philip G McTernan. 1. Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Clinical Sciences Research Laboratories, Coventry, UK.
Abstract
PURPOSE OF REVIEW: This article reviews the evidence linking gut bacteria, endotoxin, and its circulating levels with inflammatory induced obesity and metabolic disease (metabolic endotoxaemia). RECENT FINDINGS: Gut flora analyses have allowed gut microbiota signatures (GMS) to be observed in animal studies of obesity/metabolic disease. In these studies, specific GMS result in a change in obesity and metabolic disease state whereas in humans, analysis remains unclear. Serum studies, examining metabolic endotoxaemia as a biomarker, appear to link long-term cardiovascular disease and type 2 diabetes mellitus (T2DM) through activation of inflammatory pathways. More recent studies note the importance of diet, which shows the dramatic rise in endotoxin following acute or long-term high-fat diet, with the effects exacerbated in T2DM. SUMMARY: Gut flora appears to act as an important determinant in the pathogenesis of inflammatory induced obesity/T2DM. Endotoxin may act as the systemic insult, impacted by a high-fat diet, which may regulate this effect, combined with an altered GMS. As such, clinical and dietary intervention to affect this process - on the gut flora, the 'leaky' mucosal membrane and endotoxin coupled lipid absorption or removal of circulating endotoxin - could reduce the progression of inflammatory induced metabolic disease.
PURPOSE OF REVIEW: This article reviews the evidence linking gut bacteria, endotoxin, and its circulating levels with inflammatory induced obesity and metabolic disease (metabolic endotoxaemia). RECENT FINDINGS: Gut flora analyses have allowed gut microbiota signatures (GMS) to be observed in animal studies of obesity/metabolic disease. In these studies, specific GMS result in a change in obesity and metabolic disease state whereas in humans, analysis remains unclear. Serum studies, examining metabolic endotoxaemia as a biomarker, appear to link long-term cardiovascular disease and type 2 diabetes mellitus (T2DM) through activation of inflammatory pathways. More recent studies note the importance of diet, which shows the dramatic rise in endotoxin following acute or long-term high-fat diet, with the effects exacerbated in T2DM. SUMMARY: Gut flora appears to act as an important determinant in the pathogenesis of inflammatory induced obesity/T2DM. Endotoxin may act as the systemic insult, impacted by a high-fat diet, which may regulate this effect, combined with an altered GMS. As such, clinical and dietary intervention to affect this process - on the gut flora, the 'leaky' mucosal membrane and endotoxin coupled lipid absorption or removal of circulating endotoxin - could reduce the progression of inflammatory induced metabolic disease.
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