Lactobacillus plantarum CUL66 and Cholesterol Study

Lactobacillus plantarum CUL66 can impact cholesterol homeostasis in Caco-2 enterocytes

SUMMARY

Hypercholesterolemia drives the development of cardiovascular disease, the leading cause of mortality in western society, and supplementation with probiotics that interfere with cholesterol metabolism may provide a contribution to disease prevention. Lactobacillus plantarum CUL66 (NCIMB 30280) has been assessed in vitro for its ability to impact cholesterol absorption and identified as a cholesterol lowering strain by demonstrating its ability to reduce the process of cholesterol uptake in the gut intestine.

Aim

To determine the cholesterol lowering abilities of the strain L. plantarum CUL66 (NCIMB 30280) isolated from a healthy human and to assess the molecular mechanisms of its ability to reduce cholesterol uptake in an in vitro model of the intestinal epithelium.

Method

  • Cholesterol lowering ability and bile salts hydrolase (BSH) activity in plantarum CUL66 was assessed using in vitro models
  • The effect of plantarum CUL66 on cholesterol transport was assessed in an in vitro Caco-2 cell intestinal model
  • Results

    Cholesterol removal

  • Cholesterol levels in bacterial culture media were lowered in the presence of L.plantarum CUL66 (**P<0.001)
  • Bile salt hydrolase activity

  • A white precipitate was observed when plantarum CUL66 was grown in the presence of bile salts, which is indicative of BSH activity
  • Cholesterol transport

  • L.plantarum CUL66 significantly reduced the uptake of extracellular cholesterol by intestinal epithelial cells (**P<0.001)
  • L.plantarum CUL66 significantly reduced the expression of cholesterol transporter NPC1L1, which is critical for the uptake of cholesterol (*P=0.015)
  • L.plantarum CUL66 significantly reduced the efflux of intracellular cholesterol from intestinal epithelial cells into the basolateral (tissue) compartment (**P<0.001)
  • L. plantarum CUL66 significantly reduced the expression of cholesterol transporter ABCA-1, which is involved in the efflux of intracellular cholesterol to the basolateral (tissue) compartment (**P<0.001)
  • Summary of Lactobacillus plantarum CUL66 Mechanism of Action

  • CHOLESTEROL REMOVAL [cholesterol is bound or metabolised by CUL66 and subsequently excreted in faeces]
  • BILE SALT HYDROLASE ACTIVITY [deconjugation (modifying) of bile acids leads to their reduced re-absorption and places an increased demand on the liver to synthesize more bile acids from circulating cholesterol in blood to replenish intestinal bile acids lost in faeces]
  • REDUCTION OF CHOLESTEROL TRANSPORT ACROSS THE INTESTINAL EPITHELIUM [3a – reduction in the uptake of extracellular cholesterol and reduced expression of the NCP1L1 cholesterol transporter; 3b- reduction in the efflux of intracellular cholesterol to the basolateral compartment (tissues) and reduced expression of the ABCA-1 cholesterol transporter; 3c – no change on the intracellular cholesterol efflux back into the apical (intestinal lumen) compartment]
  • Conclusion

    Lactobacillus plantarum CUL66 is a very promising cholesterol lowering candidate.
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