Chylomicrons promote intestinal absorption of lipopolysaccharides

Abstract

Recent data suggest that dietary fat promotes intestinal absorption of lipopolysaccharides (LPS) from the gut microflora, which might contribute to various inflammatory disorders. The mechanism of fat-induced LPS absorption is unclear, however. Intestinal-epithelial cells can internalize LPS from the apical surface and transport LPS to the Golgi. The Golgi complex also contains newly formed chylomicrons, the lipoproteins that transport dietary longchain fat through mesenteric lymph and blood. Because LPS has affinity for chylomicrons, we hypothesized that chylomicron formation promotes LPS absorption. In agreement with our hypothesis, we found that CaCo-2 cells released more cell-associated LPS after incubation with oleic-acid (OA), a long-chain fatty acid that induces chylomicron formation, than with butyric acid (BA), a short-chain fatty acid that does not induce chylomicron formation. Moreover, the effect of OA was blocked by the inhibitor of chylomicron formation, Pluronic L-81. We also observed that intragastric triolein (TO) gavage was followed by increased plasma LPS, whereas gavage with tributyrin (TB), or TO plus Pluronic L-81, was not. Most intestinally absorbed LPS was present on chylomicron remnants (CM-R) in the blood. Chylomicron formation also promoted transport of LPS through mesenteric lymph nodes (MLN) and the production of TNFa mRNA in the MLN. Together, our data suggest that intestinal epithelial cells may release LPS on chylomicrons from cell-associated pools. Chylomicron-associated LPS may contribute to postprandial inflammatory responses or chronic diet-induced inflammation in chylomicron target tissues.-Ghoshal, S., J. Witta, J. Zhong, W. de Villiers, and E. Eckhardt. Chylomicrons promote intestinal absorption of lipopolysaccharides. J. Lipid Res. 2009. 50: 90-97.

Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages

“…Low-grade inflammation in these states may be exacerbated by circulating LPS, also known as endotoxin [2]. Lipopolysaccharide translocation from the gut to circulation is enhanced by lipid absorption [6]. Dietary SM has been studied for its effects on dyslipidemia because it reduces the absorption of other lipids (e.g., fat and cholesterol), and therefore, could potentially influence systemic inflammation.…”

“…Additionally, diets rich in triglyceride and cholesterol increase chylomicron production during digestion and absorption. It has been shown that LPS can be incorporated into chylomicrons and transported into the bloodstream of mice [6]. Overall, these effects of HFD result in the paracellular and transcellular translocation of LPS from the gut into the circulation.…”

“…These features of the gut barrier reduce permeability to LPS, which may otherwise trigger host inflammation and disease [5]. However, LPS translocation from the gut to circulation is enhanced by the absorption of dietary lipids [6]. High-fat diets (HFD) have been shown to promote inflammation of the distal intestine, causing an impairment of the protective gut barrier, and translocation of LPS into host circulation [7].…”

Functional interactions between the gut microbiota and host metabolism

“…Two hypotheses have been made to explain the mechanism: lipopolysaccharide is taken up with dietary fats in chylomicrons 70 , or lipopolysaccharide reaches the circulation because the gut is more permeable in obese mice 63 . A connection between metabolism and the function of the epithelial barrier is thought to exist.…”

Obesity and the Microbiome - A Surgeon's Perspective

“…A highfat diet results in incorporation of triglycerides into chylomicrons, which also have a high affinity for lipopolysaccharides, thus increasing lipopolysaccharide absorption and triggering metabolic inflammation. 17 In animal models, subcutaneous infusion of lipopolysaccharides resulted in weight gain, insulin resistance and induction of an inflammatory state, even without diet modification. 18 In a similar model, a high fat diet was shown to modify the proportion of BAC-related bacteria and reduce that of Bifidobacteria.…”