Effects of Lactobacillus acidophilus and Bifidobacterium bifidum probiotics on the serum biochemical parameters, and the vitamin D and leptin receptor genes on mice colon cancer

Document Type: Original Article

Authors

1 Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran

2 Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran

3 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical sciences, Tabriz, Iran

5 Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Objective(s): The preclinical reports have shown that specific probiotics like Bifidobacterium bifidum (B. bifidum) and Lactobacillus acidophilus (L. acidophilus) can be applied as the biotherapeutic agents in the inhibition or therapy of colorectal cancer via the modification of gut bacteria. In the previous studies, we have assessed the impact of L. acidophilus and B. bifidum probiotics on gut bacteria concentration and also their chemo-protective impact on mice colon cancer. In the following, we assessed the effects of these probiotics on the  gene expression of vitamin D receptor (VDR) and the leptin receptor (LPR) and the serum biochemical parameters on mice colon cancer.
Materials and Methods: Thirty-six male BALB/c mice were equally shared into 4 groups; (i) health with routine dietary foods without any treatment, (ii) azoxymethane (AOM)-induced mice colon cancer with common dietary foods, (iii) and (iv) AOM-induced mice colon cancer with oral consumption of L. acidophilus and B. bifidum (1×109 cfu/g) for 5 months, respectively. Then, the serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), alanine transaminase, alkaline phosphatase, and albumin and also VDR and LPR genes expression were evaluated.
Results: Oral consumption of L. acidophilus and B. bifidum probiotics significantly decreased the triglycerides, alkaline phosphatase, LDL, and also the VDR and LPR gene expression in mice colon cancer (P<0.005).
Conclusion: L. acidophilus and B. bifidum probiotics with the modification of the biochemical parameters and the expression of the VDR and LPR genes can play a key role in the protection of mouse colon cancer.

Keywords

Main Subjects


1. Lu R, Wu S, Xia Y, Sun J. The vitamin D receptor, inflammatory bowel diseases, and colon cancer. Curr Colorectal Cancer Rep 2012; 8:57-65.
2. Kaji R, Kiyoshima-Shibata J, Nagaoka M, Nanno M, Shida K. Bacterial teichoic acids reverse predominant IL-12 production induced by certain lactobacillus strains into predominant IL-10 production via TLR2-dependent ERK activation in macrophages. J Immunol 2010; 184:3505-3513.
3. Ranji P, Akbarzadeh A, Rahmati-Yamchi M. Associations of probiotics with vitamin D and leptin receptors and their effects on colon cancer. Asian Pac J Cancer Prev 2015; 16:3621-3627.
4. Khavari-Daneshvar H, Mosavi M, Khodayari H, Rahimi E, Ranji P, Mohseni AH, et al. Modifications of mice gut microflora following oral consumption of Lactobacillus acidophilus and Bifidobacterium bifidum probiotics. Turk J Med Sci 2017; 47:689-694.
5. Agah S, Alizadeh AM, Mosavi M, Ranji P, Khavari-Daneshvar H, Ghasemian F, et al. More Protection of Lactobacillus acidophilus than Bifidobacterium bifidum probiotics on azoxymethane-induced mouse colon cancer. Probiotics Antimicrob Proteins 2018; 10:1-8
6. Samuel S, Sitrin MD. Vitamin D’s role in cell proliferation and differentiation. Nutr Rev  2008; 66:116-124.
7. Zheng W, Wong KE, Zhang Z, Dougherty U, Mustafi R, Kong J, et al. Inactivation of the vitamin D receptor in APCmin/+ mice reveals a critical role for the vitamin D receptor in intestinal tumor growth. Int J Cancer  2012; 130:10-19.
8. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev 2008; 29:726-776.
9. Lagishetty V, Misharin AV, Liu NQ, Lisse TS, Chun RF, Ouyang Y, et al. Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis. Endocrinology 2010; 151:2423-2432.
10. Wu XZ, Ma F, Wang XL. Serological diagnostic factors for liver metastasis in patients with colorectal cancer. World J Gastroenterol 2010; 16:4084-4088.
11. Menendez C, Lage M, Peino R, Baldelli R, Concheiro P, Dieguez C, et al. Retinoic acid and vitamin D (3) powerfully inhibit in vitro leptin secretion by human adipose tissue. J Endocrinol 2001; 170:425-431.
12. Wu S, Liao AP, Xia Y, Li YC, Li J-D, Sartor RB, et al. Vitamin D receptor negatively regulates bacterial-stimulated NF-κB activity in intestine. Am J Pathol 2010; 177:686-697.
13. Hui L, Desen W, Zhizhong P, Lijing C, Xiaojun W, Zhenhai L, et al. Expression and biological significance of leptin, leptin receptor, VEGF, and CD34 in colorectal carcinoma. Cell Biochem Biophys 2011; 60:241-244.
14. Endo H, Hosono K, Uchiyama T, Sakai E, Sugiyama M, Takahashi H, et al. Leptin acts as a growth factor for colorectal tumours at stages subsequent to tumour initiation in murine colon carcinogenesis. Gut 2011; 60:1363-1371.
15. Bolukbas FF, Kilic H, Bolukbas C, Gumus M, Horoz M, Turhal NS, et al. Serum leptin concentration and advanced gastrointestinal cancers: a case controlled study. BMC Cancer 2004; 4:29.
16. Kumar M, Nagpal R, Verma V, Kumar A, Kaur N, Hemalatha R, et al. Probiotic metabolites as epigenetic targets in the prevention of colon cancer. Nutr Rev 2013; 71:23-34.
17. Drew JE. Molecular mechanisms linking adipokines to obesity-related colon cancer: focus on leptin. Proc Nutr Soc 2012; 71:175-180.
18. Matsunuma A, Horiuchi N. Leptin attenuates gene expression for renal 25-hydroxyvitamin D 3-1α-hydroxylase in mice via the long form of the leptin receptor. Arch Biochem Biophys 2007; 463:118-127.
19. Heydari Z, Alizadeh AM, Agah SH, Khalighfard  S, Bahmani S. Effects of Lactobacillus acidophilus and Bifidobacterium bifidum probiotics on the expression of microRNAs 135b, 26b, 18a and 155, and their involving genes in mice colon cancer. Probiotics Antimicrob Proteins 2018; 1-8.
20. Kavosi A, Noei SH, Madani S, Khalighfard S, Khodayari S, Khodayari H, et al. The toxicity and therapeutic effects of single-and multi-wall carbon nanotubes on mice breast cancer. Sci Rep 2018; 8:8375.
21. Mohsenikia M, Farhangi B, Alizadeh AM, Khodayari H, Khodayari S, Khori V, et al. Therapeutic effects of dendrosomal solanine on a metastatic breast tumor. Life Sci 2016; 148:260-267.
22. Khori V, Shalamzari SA, Isanejad A, Alizadeh AM, Alizadeh S, Khodayari S, et al. Effects of exercise training together with tamoxifen in reducing mammary tumor burden in mice: Possible underlying pathway of miR-21. Eur J Pharm 2015; 765:179-187.
23. Chen Z-Y, Hsieh Y-M, Huang C-C, Tsai C-C. Inhibitory effects of probiotic Lactobacillus on the growth of human colonic carcinoma cell line HT-29. Molecules 2017; 22:107.
24. Di W, Zhang L, Yi H, Han X, Zhang Y, Xin L. Exopolysaccharides produced by Lactobacillus strains suppress HT-29 cell growth via induction of G0/G1 cell cycle arrest and apoptosis. Oncol Lett 2018; 16:3577-3586.
25. El-Deeb NM, Yassin AM, Al-Madboly LA, El-Hawiet A. A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-kappaB inflammatory pathways in human colon cancer. Microb Cell Fact 2018; 17:29.
26. Sun ZJ, Huang YH, Wu JS, Yang YC, Chang YF, Lu FH, et al. The association of serum lipids with the histological pattern of rectosigmoid adenoma in Taiwanese adults. BMC Gastroenterol 2011; 11:54.
27. Awaisheh S, Khalifeh M, Al-Ruwaili M, Khalil O, Al-Ameri O, Al-Groom R. Effect of supplementation of probiotics and phytosterols alone or in combination on serum and hepatic lipid profiles and thyroid hormones of hypercholesterolemic rats. J Dairy Sci 2013; 96:9-15.
28. Ejtahed H, Mohtadi-Nia J, Homayouni-Rad A, Niafar M, Asghari-Jafarabadi M, Mofid V, et al. Effect of probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis on lipid profile in individuals with type 2 diabetes mellitus. J Dairy Sci 2011; 94:3288-3294.
29. Turner P, Wu Q, Piekkola S, Gratz S, Mykkänen H, El-Nezami H. Lactobacillus rhamnosus strain GG restores alkaline phosphatase activity in differentiating Caco-2 cells dosed with the potent mycotoxin deoxynivalenol. Food Chem Toxicol 2008; 46:2118-2123.
30. Oda T, Seto Y, Hashiba H. Supplementation of Bifidobacterium longum to a high-fat, low-calcium diet lowers cytolytic activity of fecal water in rats injected with 1, 2-dimethylhydrazine dihydrochloride. J Nutr Sci Vitaminol (Tokyo) 1998; 44:187-194.
31. An HM, Park SY, Lee DK, Kim JR, Cha MK, Lee SW, et al. Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats. Lipids Health Dis 2011; 10:116.
32. Li C, Li J, Bai P, Lv Y. Characteristic analysis of plasma lipid metabolism level in patients with colorectal adenoma. Beijing Da Xue Xue Bao 2011; 43:432-435.
33. Appleyard CB, Cruz ML, Isidro AA, Arthur JC, Jobin C, De Simone C. Pretreatment with the probiotic VSL# 3 delays transition from inflammation to dysplasia in a rat model of colitis-associated cancer. Am J Physiol Gastrointest Liver Physiol 2011; 301:1004-1013.
34. Bartucci M, Svensson S, Ricci-Vitiani L, Dattilo R, Biffoni M, Signore M, et al. Obesity hormone leptin induces growth and interferes with the cytotoxic effects of 5-fluorouracil in colorectal tumor stem cells. Endocr Relat Cancer 2010; 17:823-833.
35. Joshi RK, Lee S-A. Obesity related adipokines and colorectal cancer: a review and meta-analysis. Asian Pac J Cancer Prev 2014; 15:397-405.
36. Slattery M, Ballard-Barbash R, Edwards S, Caan BJ, Potter JD. Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States). Cancer Causes Control 2003; 14:75-84.
37. Mencarelli A, Distrutti E, Renga B, D’Amore C, Cipriani S, Palladino G, et al. Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation. PLoS One 2011; 6:e22978.