Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents development of atherosclerosis in high-fat diet-fed apoE-deficient mice via ameliorating hyperlipidemia, pro-inflammatory mediators and oxidative responses

Abstract

Pantoea agglomerans (P. agglomerans) is a Gram-negative bacterium that grows symbiotically with various edible plants, and the oral or sublingual administration of lipopolysaccharide derived from P. agglomerans (LPSp) have been suggested to contribute to prevention of immune-related diseases. Our previous study indicated that orally administered LPSp was shown to exhibit an LDL-lowering effect in hyperlipidemic volunteers; however, a preventive effect of LPSp on atherosclerosis is unclear. The present study attempted to evaluate the anti-atherosclerotic effect by LPSp in a mouse model of high-fat diet (HFD)-induced atherosclerosis. For 16 weeks, apoE-deficient mice were fed an HFD and received drinking water containing LPSp (0.3 or 1 mg/kg body weight/day). The results showed that the orally administered LPSp decreased body weight. A significant reduction in atherosclerotic plaque deposition was observed even with the lower dose of LPSp. The biochemical analyses showed that LPSp markedly improved glucose tolerance and reduced plasma LDL and oxidized LDL levels. In addition, LPSp significantly reduced the production of pro-inflammatory mediators including MCP-1 (in the plasma), TNF-α and IL-6 (in the colon), and decreased the oxidative burst activities in the peripheral blood sample. Taken together, these results suggest the possibility that oral administration of LPSp can effectively ameliorate HFD-induced hyperlipidemia and inflammatory/oxidative responses to prevent atherosclerosis and related metabolic disorders.

Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents metabolic dysfunction and Alzheimer’s disease-related memory loss in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet

“…A growing body of evidence indicates that SAMP8 mice exhibit AD-like pathology and cognitive decline that result from aging and oxidative stress without genetic factors that act proximally on AD etiology [ 30 ]. Considering that orally administered LPSp has a beneficial effect on glucose/lipid metabolism [ 16 ], the present study used SAMP8 mice as a mouse model of AD to evaluate LPSp effects on HFD-induced AD progression. Consistent with recent studies using an HFD-fed SAMP8 [ 21 , 31 ], the present data demonstrated that chronic HFD feeding induces a significant increase in BW, caloric intake, fasting insulin level, HbA1c, and the glucose AUC in the OGTT, which is associated with an impairment of memory performance in the MWM test.…”

“…The drinking water was changed weekly, and the concentration of LPSp was adjusted according to the average BW and amount of water consumption. The dose of LPSp was determined to be the sufficient dose required to achieve preventive effects as estimated from previous studies (0.1–1 mg/kg BW/day) [ 8 , 10 , 16 ]. BW, food intake, and water intake were recorded weekly.…”

“…O 2 · - production and MPO activity in the peripheral blood samples were simultaneously determined after stimulation with phorbol 12-myristate 13-acetate (PMA; Wako Pure Chemical Industries) using a real-time chemiluminescence and fluorescence monitoring system (CFL-P2200; Hamamatsu Photonics K.K., Shizuoka, Japan), as previously described [ 16 ]. Briefly, an aliquot of each whole blood sample (30 μl) was incubated with 500 μl of an ammonium chloride-based red-blood-cell lysis buffer with no fixing reagents (Tonbo Biosciences, Inc., San Diego, CA, USA) for 2 min at room temperature (RT), and the cells were then pelleted by centrifugation (200 × g for 5 min at RT).…”

“…Many epidemiological data [ 15 ] support the association of cardiovascular risk factors (diabetes mellitus, hyperlipidemia, and hypertension) with AD pathogenesis such as amyloidosis and cognitive decline, suggesting an impairment of glucose/lipid metabolism contributes to AD by accelerating an oxidative-stress and inflammatory response, leading to Aβ deposition and neural dysfunction. Our recent in vivo study demonstrated that oral administration of LPSp prevented the development of atherosclerosis via reducing hyperlipidemia, pro-inflammatory mediators and oxidative responses in high-fat diet (HFD)-fed mice [ 16 ]. Other studies also reported that oral treatment with a heat shock protein (HSP; known as a TLR4 agonist) prevents the development of diabetes mellitus and hyperlipidemia by improving glucose/lipid metabolism and reducing inflammatory responses in mice [ 17 , 18 ], however few studies have shown a preventive effect on AD progression by orally administered TLR4 agonists.…”

Comprehensive genomic analysis reveals virulence factors and antibiotic resistance genes inPantoea agglomeransKM1, a potential opportunistic pathogen

“…P. agglomerans derived LPS has anti-cancer properties in B16 melanoma model in mice [20], and an oral administration of this molecule contributed to prevention of atherosclerosis and hypertension [21].…”