Skip to main content
Log in

Lactiplantibacillus plantarum PGB02 Improved Serum Cholesterol Profile by Tweaking Genes Involved in Cholesterol Homeostasis in Male Swiss Albino Mice

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

The effect of Lactiplantibacillus plantarum PGB02 isolated from buttermilk on serum cholesterol profile of normal and hypercholesterolemic mice was evaluated. Further changes in the expression of mice genes were determined. The hypercholesterolemia was induced in experimental mice by feeding high cholesterol and fat diet. Serum cholesterol parameters, physical parameters, cholic acid excretion, and cholesterol metabolism related gene expression analysis was carried out. L. plantarum PGB02 efficiently reduced total cholesterol, triglycerides, and LDL-cholesterol and improved HDL-cholesterol in hypercholesterolaemic mice. Body weight was reduced and fecal cholic acid increased in probiotic treatment groups. Gene expression analysis revealed that L. plantarum PGB02 up-regulated the expression of LDL receptors, CYP7A1, ABCA1, ABCG5, ABCG8, and down-regulated the expression of FXR and NPC1L1 genes. Summarizing the mechanism, L. plantarum PGB02 improved hypercholesterolemia by increasing bile acid synthesis and excretion, reducing exogeneous cholesterol absorption from the intestine, and increased LDL clearance through upregulation of LDL-receptors. The present study has given insight into the mechanism of serum cholesterol reduction by bile salt hydrolase positive L. plantarum PGB02 in mice. L. plantarum PGB02 reduced the serum cholesterol level through increased bile acid synthesis and deconjugation and reduced absorption of cholesterol in the intestine. Isolate PGB02 shown cholesterol removal potential as good as statin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

There are no additional datasets associated with this study.

References

  1. WHO. (2021). fact sheet, Cardiovascular diseases (CVDs). https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds). Accessed 7 May 2022.

  2. Michael, D. R., et al. (2017). The anti-cholesterolaemic effect of a consortium of probiotics: An acute study in C57BL/6J mice. Science and Reports, 7, 1–10. https://doi.org/10.1038/s41598-017-02889-5

    Article  CAS  Google Scholar 

  3. Banach, M., et al. (2015). Statin intolerance - an attempt at a unified definition. Archives of Medical Science, 11, 1–23. https://doi.org/10.5114/aoms.2015.49807

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kumar, M., et al. (2013). Probiotic Lactobacillus rhamnosus GG and Aloe vera gel improve lipid profiles in hypercholesterolemic rats. Nutrition, 29, 574–579. https://doi.org/10.1016/j.nut.2012.09.006

    Article  CAS  PubMed  Google Scholar 

  5. Fabian, E., & Elmadfa, I. (2006). Influence of daily consumption of probiotic and conventional yoghurt on the plasma lipid profile in young healthy women. Annals of Nutrition & Metabolism, 50, 387–393. https://doi.org/10.1159/000094304

    Article  CAS  Google Scholar 

  6. Marteau, P. (2001). Safety aspects of probiotic products. Näringsforskning, 45, 22–24. https://doi.org/10.3402/fnr.v45i0.1785

    Article  Google Scholar 

  7. Pereira, D. I. A., & Gibson, G. R. (2002). Cholesterol assimilation by lactic acid bacteria and bifidobacteria isolated from the human gut. Applied and Environment Microbiology, 68, 4689–4693. https://doi.org/10.1128/AEM.68.9.4689-4693.2002

    Article  CAS  Google Scholar 

  8. Rani, R. P., Anandharaj, M., & Ravindran, A. D. (2017). Characterization of bile salt hydrolase from Lactobacillus gasseri FR4 and demonstration of its substrate specificity and inhibitory mechanism using molecular docking analysis. Frontiers in Microbiology, 8, 1–13. https://doi.org/10.3389/fmicb.2017.01004

    Article  Google Scholar 

  9. Liong, M. T., & Shah, N. P. (2006). Effects of a Lactobacillus casei synbiotic on serum lipoprotein, intestinal microflora, and organic acids in rats. Journal of Dairy Science, 89, 1390–1399. https://doi.org/10.3168/JDS.S0022-0302(06)72207-X

    Article  CAS  PubMed  Google Scholar 

  10. De Preter, V. et al. (2007). Effects of Lactobacillus casei Shirota, Bifidobacterium breve, and oligofructose-enriched inulin on colonic nitrogen-protein metabolism in healthy humans, American Journal of Physiology-Gastrointestinal and Liver Physiology, 292. https://doi.org/10.1152/AJPGI.00052.2006

  11. Pereira, D. I. A., & Gibson, G. R. (2002). Effects of consumption of probiotics and prebiotics on serum lipid levels in humans. Critical Reviews in Biochemistry and Molecular Biology, 37, 259–281. https://doi.org/10.1080/10409230290771519

    Article  CAS  PubMed  Google Scholar 

  12. Choi, S. B., Lew, L. C., Yeo, S. K., Parvathy, S. N., & Liong, M. T. (2015). Probiotics and the BSH-related cholesterol lowering mechanism: A Jekyll and Hyde scenario. Critical Reviews in Biotechnology, 35, 392–401. https://doi.org/10.3109/07388551.2014.889077

    Article  CAS  PubMed  Google Scholar 

  13. Lew, L. C., et al. (2018). Lactobacillus plantarum DR7 reduces cholesterol via phosphorylation of AMPK that down-regulated the mRNA expression of HMG-CoA reductase. Korean Journal for Food Science of Animal Resources, 38, 350. https://doi.org/10.5851/KOSFA.2018.38.2.350

    Article  PubMed  PubMed Central  Google Scholar 

  14. Xu, G. et al. (2004). Dietary cholesterol stimulates CYP7A1 in rats because farnesoid X receptor is not activated. American Journal of Physiology. Gastrointestinal and Liver Physiology, 286. https://doi.org/10.1152/AJPGI.00397.2003

  15. Huang, Y., & Zheng, Y. (2010). The probiotic Lactobacillus acidophilus reduces cholesterol absorption through the down-regulation of Niemann-Pick C1-like 1 in Caco-2 cells. British Journal of Nutrition, 103, 473–478. https://doi.org/10.1017/S0007114509991991

    Article  CAS  PubMed  Google Scholar 

  16. Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry, 18, 499–502. https://doi.org/10.1093/clinchem/18.6.499

    Article  CAS  PubMed  Google Scholar 

  17. Kumar, R., Grover, S., & Batish, V. K. (2011). Hypocholesterolaemic effect of dietary inclusion of two putative probiotic bile salt hydrolase-producing Lactobacillus plantarum strains in Sprague-Dawley rats. British Journal of Nutrition, 105, 561–573. https://doi.org/10.1017/S0007114510003740

    Article  CAS  PubMed  Google Scholar 

  18. Jeun, J., et al. (2010). Hypocholesterolemic effects of Lactobacillus plantarum KCTC3928 by increased bile acid excretion in C57BL/6 mice. Nutrition, 26, 321–330. https://doi.org/10.1016/j.nut.2009.04.011

    Article  CAS  PubMed  Google Scholar 

  19. Yan, F., et al. (2019). Lactobacillus acidophilus alleviates type 2 diabetes by regulating hepatic glucose, lipid metabolism and gut microbiota in mice. Food & Function, 10, 5804–5815. https://doi.org/10.1039/C9FO01062A

    Article  CAS  Google Scholar 

  20. Clayton, P. T. (1998). Disorders of cholesterol biosynthesis. Archives of Disease in Childhood, 78, 185–189. https://doi.org/10.1136/adc.78.2.185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. McCrindle, B. W., Ose, L., & Marais, A. D. (2003). Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: A multicenter, randomized, placebo-controlled trial. Journal of Pediatrics, 143, 74–80. https://doi.org/10.1016/S0022-3476(03)00186-0

    Article  CAS  PubMed  Google Scholar 

  22. Silverman, M. G., et al. (2016). Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: A systematic review and meta-analysis, JAMA -. Journal of the American Medical Association, 316, 1289–1297. https://doi.org/10.1001/jama.2016.13985

    Article  CAS  PubMed  Google Scholar 

  23. Chand, D., et al. (2017). Molecular features of bile salt hydrolases and relevance in human health. Biochim. Biophys. Acta - Gen. Subj., 1861, 2981–2991. https://doi.org/10.1016/j.bbagen.2016.09.024

    Article  CAS  PubMed  Google Scholar 

  24. Cohen, J. C., et al. (1992). Cloning of the human cholesterol 7α-hydroxylase gene (CYP7) and localization to chromosome 8q11–q12. Genomics, 14, 153–161. https://doi.org/10.1016/S0888-7543(05)80298-8

    Article  CAS  PubMed  Google Scholar 

  25. Angelin, B., Hershont, K. S., & Brunzellt, J. D. (1987). Bile acid metabolism in hereditary forms of hypertriglyceridemia: Evidence for an increased synthesis rate in monogenic familial hypertriglyceridemia. Proceedings of the National Academy of Sciences, 84, 5434–5438. https://doi.org/10.1073/pnas.84.15.5434

    Article  CAS  Google Scholar 

  26. Bell, G. D., Lewis, B., Petrie, A., & Dowling, R. H. (1973). Serum lipids in cholelithiasis: Effect of chenodeoxycholic acid therapy. British Medical Journal, 3, 520–523. https://doi.org/10.1136/BMJ.3.5879.520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bateson, M., Maclean, D., Evans, J., & Bouchier, I. (1978). Chenodeoxycholic acid therapy for hypertriglyceridaemia in men. British Journal of Clinical Pharmacology, 5, 249–254. https://doi.org/10.1111/J.1365-2125.1978.TB01632.X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Crouse, J. R. (1987). Hypertriglyceridemia: A contraindication to the use of bile acid binding resins. American Journal of Medicine, 83, 243–248. https://doi.org/10.1016/0002-9343(87)90692-9

    Article  PubMed  Google Scholar 

  29. Beil, U., Crouse, J. R., Einarsson, K., & Grundy, S. M. (1982). Effects of interruption of the enterohepatic circulation of bile acids on the transport of very low density-lipoprotein triglycerides. Metabolism, 31, 438–444. https://doi.org/10.1016/0026-0495(82)90231-1

    Article  CAS  PubMed  Google Scholar 

  30. Young, S. G., & Fielding, C. J. (1999). The ABCs of cholesterol efflux. Nature Genetics, 22, 316–318. https://doi.org/10.1038/11878

    Article  CAS  PubMed  Google Scholar 

  31. Rust, S., et al. (1999). Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nature Genetics, 22, 352–355. https://doi.org/10.1038/11921

    Article  CAS  PubMed  Google Scholar 

  32. Jiao, Y., Lu, Y., & Li, X. Y. (2015). Farnesoid X receptor: A master regulator of hepatic triglyceride and glucose homeostasis. Acta Pharmacologica Sinica., 36, 44–50. https://doi.org/10.1038/aps.2014.116

    Article  CAS  PubMed  Google Scholar 

  33. DiMarzio, M. et al. (2017) Identification of a mouse Lactobacillus johnsonii strain with deconjugase activity against the FXR antagonist T-β-MCA. PLoS ONE, 12.https://doi.org/10.1371/journal.pone.0183564

  34. Sinal, C. J., et al. (2000). Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell, 102, 731–744. https://doi.org/10.1016/S0092-8674(00)00062-3

    Article  CAS  PubMed  Google Scholar 

  35. Zein, A. A., Kaur, R., Hussein, T. O. K., Graf, G. A., & Lee, J.-Y. (2019). ABCG5/G8: A structural view to pathophysiology of the hepatobiliary cholesterol secretion. Biochemical Society Transactions, 47, 1259–1268. https://doi.org/10.1042/BST20190130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Degirolamo, C., Rainaldi, S., Bovenga, F., Murzilli, S., & Moschetta, A. (2014). Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr-Fgf15 axis in mice. Cell Reports, 7, 12–18. https://doi.org/10.1016/j.celrep.2014.02.032

    Article  CAS  PubMed  Google Scholar 

  37. Liang, X., et al. (2020). Probiotics improved hyperlipidemia in mice induced by a high cholesterol diet via downregulating FXR. Food and Function, 11, 9903–9911. https://doi.org/10.1039/D0FO02255A

    Article  CAS  PubMed  Google Scholar 

  38. Martoni, C. J., Labbé, A., Ganopolsky, J. G., Prakash, S., & Jones, M. L. (2015). Changes in bile acids, FGF-19 and sterol absorption in response to bile salt hydrolase active L. reuteri NCIMB 30242. Gut Microbes, 6, 57–65. https://doi.org/10.1080/19490976.2015.1005474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Hiren Dhameliya: conceptualization, methodology, and manuscript preparation; Jyoti Solanki: methodology and work-plan preparation; Dhaval Patel: methodology and conceptualization; Linz-buoy George: methodology and supervision; Vasudev Thakkar: supervision and validation; R. B. Subramanian: conceptualization, reviewing and editing.

Corresponding author

Correspondence to R. B. Subramanian.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Ethics Approval

The study protocol was approved by Institutional Animal Ethics Committee, under registration No. 167/199/CPCSEA from the Committee for the Purpose of Control and Supervision of Experiments on Animals, Delhi, India.

Consent to Participate

Not applicable.

Consent to Publish

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 21 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dhameliya, H.A., Solanki, J.D., Patel, D.T. et al. Lactiplantibacillus plantarum PGB02 Improved Serum Cholesterol Profile by Tweaking Genes Involved in Cholesterol Homeostasis in Male Swiss Albino Mice. Appl Biochem Biotechnol 195, 3180–3193 (2023). https://doi.org/10.1007/s12010-022-04307-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-022-04307-7

Keywords

Navigation