LPS / metabolic endotoxemia

Lipopolysaccharide (LPS) is a building block of the outer wall of Gram-negative bacteria. When bacteria die or divide and shed it, LPS is the single most potent trigger for an immune receptor called TLR4. It is a primary driver of the inflammatory storm in sepsis. 'Metabolic endotoxemia' is a milder, chronic version. The term was coined by Cani and colleagues in a 2007 Diabetes paper. It describes a low but persistently raised blood LPS (2 to 3 times the fasting baseline), arising from a leaky gut barrier and from LPS hitching a ride on fat-carrying particles after high-fat meals. That low-grade TLR4 activation, on liver cells, fat cells, and macrophages, promotes insulin resistance, fat-tissue inflammation, and fatty liver in rodent models. You may have heard 'leaky gut' as shorthand for increased gut permeability. It is a popular phrase, but informal and imprecise. The real barrier is run by tight-junction proteins (occludin, claudins, ZO-1). When those drop, and the mucus layer thins, the barrier weakens, and certain diets and dysbiosis can do exactly that. In humans, the evidence for a causal endotoxemia-to-disease path is supportive but not conclusive, and blood LPS is hard to measure accurately.

Last reviewed: June 22, 2026

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