Bacterial Endotoxin Activity in Human Serum Is Associated With Dyslipidemia, Insulin Resistance, Obesity, and Chronic Inflammation

Abstract

OBJECTIVETo investigate whether bacterial lipopolysaccharide (LPS) activity in human serum is associated with the components of the metabolic syndrome (MetS) in type 1 diabetic patients with various degrees of kidney disease and patients with IgA glomerulonephritis (IgAGN).RESEARCH DESIGN AND METHODSSerum LPS activity was determined with the Limulus Amoebocyte Lysate chromogenic end point assay in type 1 diabetic patients with a normal albumin excretion rate (n = 587), microalbuminuria (n = 144), macroalbuminuria (n = 173); patients with IgAGN (n = 98); and in nondiabetic control subjects (n = 345). The relationships of the LPS/HDL ratio and MetS-associated variables were evaluated with Pearson correlation.RESULTSThe MetS was more prevalent in type 1 diabetic patients (48%) than in patients with IgAGN (15%). Diabetic patients with macroalbuminuria had a significantly higher serum LPS/HDL ratio than patients with IgAGN. In the normoalbuminuric type 1 diabetic group, patients in the highest LPS/HDL quartile were diagnosed as having the MetS three times more frequently than patients in the lowest quartile (69 vs. 22%; P < 0.001). High LPS activity was associated with higher serum triglyceride concentration, earlier onset of diabetes, increased diastolic blood pressure, and elevated urinary excretion of monocyte chemoattractant protein-1.CONCLUSIONSHigh serum LPS activity is strongly associated with the components of the MetS. Diabetic patients with kidney disease seem to be more susceptible to metabolic endotoxemia than patients with IgAGN. Bacterial endotoxins may thus play an important role in the development of the metabolic and vascular abnormalities commonly seen in obesity and diabetes-related diseases.

Small Intestinal Bacterial Overgrowth Is Associated with Non- Alcoholic Fatty Liver Disease

“…Similar results were found when the gut microbiome of human twins discordant for obesity was transferred to germ-free mice [34]. Furthermore, studies in mice and in humans have shown that gut bacteria may contribute to other components of the metabolic syndrome, such as insulin resistance and type 2 DM through elevated levels of LPS [5,6], leading to an inflammatory state in the host [7,31,35].…”

The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: an open label, randomized pilot study

“…11 Those increased endotoxin levels may further trigger inflammatory reactions and/or immune dysfunction. 12 This is also underlined by impaired cell-mediated immune responses in vivo and in vitro and a reduced intracellular killing by neutrophils. 13 Weight loss is the most effective therapy of obesity, which also influences gut microbiota composition 14 and improves monocyte function.…”

Acid sphingomyelinase plays a key role in palmitic acid-amplified inflammatory signaling triggered by lipopolysaccharide at low concentrations in macrophages

“…Interestingly, clinical studies have shown that circulating LPS is increased in patients with obesity (21,33), and animal studies have shown that TLR4 deficiency in mice protects against the development of insulin resistance (41). Taking these clinical and animal findings together, it is indicated that TLR4 signaling triggered by low concentrations of LPS may contribute to the inflammatory state that is essential for developing insulin resistance (50).…”