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

PLoS One. 2018 Mar 27;13(3):e0195008. doi: 10.1371/journal.pone.0195008. eCollection 2018.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics*
  • Body Weight / drug effects
  • Chemokine CCL2 / blood
  • Diet, High-Fat*
  • Hyperlipidemias / etiology
  • Hyperlipidemias / prevention & control
  • Interleukin-6 / analysis
  • Interleukin-6 / blood
  • Intestines / microbiology
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology*
  • Lipoproteins, LDL / blood
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Oxidative Stress / drug effects*
  • Pantoea / metabolism*
  • Plaque, Atherosclerotic / etiology
  • Plaque, Atherosclerotic / prevention & control*
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Apolipoproteins E
  • Chemokine CCL2
  • Interleukin-6
  • Lipopolysaccharides
  • Lipoproteins, LDL
  • Tumor Necrosis Factor-alpha
  • oxidized low density lipoprotein

Associated data

  • Dryad/10.5061/dryad.1ts48

Grant support

This work was supported by the Council for Science, Technology and Innovation (CSTI), Cross-ministerial Strategic Innovation Promotion Program (SIP) and ‘Technologies for creating next-generation agriculture, forestry and fisheries’ (funding agency: Bio-oriented Technology Research Advancement Institution, NARO). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CK is employed by Macrophi Inc. The funder provided support in the form of salary for author CK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. KK, HT and TM are employed by Hamamatsu Photonics K.K. The funder provided support in the form of salaries for authors KK, HT and TM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.