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 L. plantarum CUL66 was assessed using in vitro models
  • The effect of L. 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 L. 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 synthesise 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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