Effect of a Natural Inulin-Containing Product, “Kikuimo Extract” on Intestinal Microbes and Gene Expression in the Liver and Adipose Tissue of Menopausal Monkeys — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Effect of a Natural Inulin-Containing Product, “Kikuimo Extract” on Intestinal Microbes and Gene Expression in the Liver and Adipose Tissue of Menopausal Monkeys
Nihontounyoushoken Co. Ltd., Iida, Japan
,
Primate Research Institute, Kyoto University, Inuyama, Japan
,
Oasis Co. Ltd., Takarazuka, Japan
,
NPO Primate Agora, Inuyama, Japan
,
Intelligence and Technology Lab Inc., Kaizu, Japan
1 Nihontounyoushoken Co. Ltd., Iida, Japan
2 Primate Research Institute, Kyoto University, Inuyama, Japan
3 Oasis Co. Ltd., Takarazuka, Japan
4 NPO Primate Agora, Inuyama, Japan
5 Intelligence and Technology Lab Inc., Kaizu, Japan
Inulin is a soluble and indigestible fiber derived from natural plants such as Jerusalem artichoke ( Helianthus tuberosus ), “Kikuimo”. In the current study, a nutrigenomics approach was utilized to evaluate the in vivo function of “Kikuimo Extract” (KE) in ovariectomized cynomolgus macaque, a post-menopausal non-human primate model. KE was administered orally before feeding, for 3 months for the following examinations: 1) the effect of KE on intestinal microbes was examined by quantitative analyses of the intestinal bacteria using real-time PCR with DNA extracted from monkey feces; 2) the effect of KE on gene expression was investigated by real-time RT-PCR using RNA extracted from both the liver and adipose tissue of the monkeys. KE administration modulated menopause-mediated altered microbes to increase Lactobacilli, Veillonella , and Bacteroides in all monkeys. KE administration regulated the altered expression of functional genes, SCAP, LDLR, and LXRA (lipid metabolism); GLUT -4 (glucose transport); CYP1A 1 and CYP1A 2 (drug metabolism); and CYP -17-2 and CYP -19-2 (E2 synthesis) in the menopausal monkeys. In menopausal monkeys, KE showed potent prebiotic effect on beneficial microflora and regulating effect on altered expression of functional genes associated with metabolism and E2 production. Thus, KE appears to be a practical functional food that alleviates the altered conditions of intestinal microbes and gene expression in the liver and adipose tissue in a menopausal state.
Calub, T.M., Waterhouse, A.L. and French, A.D. (1990) Conformational Analysis of Inulobiose by Molecular Mechanics. Carbohydrate Research, 207, 221-235. http://dx.doi.org/10.1016/0008-6215(90)84050-5
Liu, J., Waterhouse, A.L. and Chatterton, N.J. (1993) Proton and Carbon NMR Chemical-Shift Assignments for [Beta- D-Fru f-(2-->1)]3-(2 1)-Alpha-D-Glc p (Nystose) and [Beta-D-Fru f-(2-->1)] 4-(2 1)-Alpha-D-Glc p (1,1,1- Kestopentaose) from Two-Dimensional NMR Spectral Measurements. Carbohydrate Research, 245, 11-19. http://dx.doi.org/10.1016/0008-6215(93)80056-K
Roberfroid, M.B. (2005) Introducing Inulin-Type Fructans. The British Journal of Nutrition, 93, S13-S25. http://dx.doi.org/10.1079/bjn20041350
Kleessen, B., Svkura, B., Zunft, H.-J. and Blaut, M. (1997) Effects of Inulin and Lactose on Fecal Microflora, Microbial Activity, and Bowel Habit in Elderly Constipated Persons. The American Journal of Clinical Nutrition, 65, 1397-1402.
Niness, K.R. (1999) Inulin and Oligofructose: What Are They? The Journal of Nutrition, 129, 1402S-1406S.
Kleessen, B., Hartmann, L. and Blaut, M. (2001) Oligofructose and Long-Chain Inulin: Influence on the Intestinal Microbial Ecology of Rats Associated with a Human Faecal Flora. The British Journal of Nutrition, 86, 291-300. http://dx.doi.org/10.1079/BJN2001403
Langlands, S.J., Hopkins, M.J., Coleman, N. and Cummings, J.H. (2004) Prebiotic Carbohydrates Modify the Mucosa Associated Microflora of the Human Large Bowel. Gut, 53, 1610-1616. http://dx.doi.org/10.1136/gut.2003.037580
Lesniewska, V., Rowland, I., Cani, P.D., Neyrinck, A.M., Delzenne, N.M. and Naughton, P.J. (2006) Effect on Components of the Intestinal Microflora and Plasma Neuropeptide Levels of Feeding Lactobacillus delbrueckii, Bifidobacterium lactis, and Inulin to Adult and Ederly Rats. Applied and Environmental Microbiology, 72, 6533-6538. http://dx.doi.org/10.1128/AEM.00915-06
Gibson, G.R. and Roberfroid, M.B. (1995) Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics. The Journal of Nutrition, 125, 1401-1412.
Zutshi, M., Hull, T.L., Bast, J. and Hammel, J. (2007) Female Bowel Function: The Real Story. Diseases of the Colon and Rectum, 50, 351-358. http://dx.doi.org/10.1007/s10350-006-0758-0
Matsumoto, S., Watanabe, N., Imaoka, A. and Okabe, Y. (2001) Preventive Effects of Bifidobacterium- and Lactobacillus-Fermented Milk on the Development of Inflammatory Bowel Disease in Senescence-Accelerated Mouse P1/Yit Strain Mice. Digestion, 64, 92-99. http://dx.doi.org/10.1159/000048846
Lu, L. and Walker, W.A. (2001) Pathologic and Physiologic Interactions of Bacteria with the Gastrointestinal Epithelium. The American Journal of Nutrition, 73, 1124S-1130S.
deMoreno de LeBlanc, A., Matar, C. and Perdigón, G. (2007) The Application of Probiotics in Cancer. The British Journal of Nutrition, 98, S105-S110. http://dx.doi.org/10.1017/s0007114507839602
Biarc, J., Nguyen, I.S., Pini, A., Gossé, F., Richert, S., Thiersé, D., Van Dorsselaer, A., Leize-Wagner, E., Raul, F., Klein, J.P. and Schöller-Guinard, M. (2004) Carcinogenic Properties of Proteins with Pro-Inflammatory Activity from Streptococcus infantarius (Formerly S. bovis). Carcinogenesis, 25, 1477-1484. http://dx.doi.org/10.1093/carcin/bgh091
Kleessen, B., Hartmann, L. and Blaut, M. (2003) Fructans in the Diet Cause Alterations of Intestinal Mucosal Architecture, Released Mucins and Mucosa-Associated Bifidobacteria in Gnotobiotic Rats. The British Journal of Nutrition, 89, 597-606. http://dx.doi.org/10.1079/BJN2002827
Geboes, K.P., De Hertogh, G., De Preter, V., Luypaerts, A., Bammens, B., Evenepoel, P., Ghoos, Y., Geboes, K., Rutgeerts, P. and Verbeke, K. (2006) The Influence of Inulin on the Absorption of Nitrogen and the Production of Metabolites of Protein Fermentation in the Colon. The British Journal of Nutrition, 96, 1078-1086. http://dx.doi.org/10.1017/BJN20061936
Sauer, J., Richter, K.K. and Pool-Zobel, B.L. (2007) Products Formed during Fermentation of the Prebiotic Inulin with Human Intestinal Flora Enhance Expression of Biotransformation Genes in Human Primary Colon Cells. The British Journal of Nutrition, 97, 928-937. http://dx.doi.org/10.1017/S0007114507666422
Geier, M.S., Butler, R.N. and Howarth, G.S. (2006) Probiotics, Prebiotics and Synbiotics: A Role in Chemoprevention for Colorectal Cancer? Cancer Biology & Therapy, 5, 1265-1269. http://dx.doi.org/10.4161/cbt.5.10.3296
Scholz-Ahrens, K.E., Schaafsma, G., van den Heuvel, E.G. and Schrezenmeir, J. (2001) Effects of Prebiotics on Mineral Metabolism. The American Journal of Clinical Nutrition, 73, 459S-464S.
Beylot, M. (2005) Effects of Inulin-Type Fructans on Lipid Metabolism in Man and in Animal Models. The British Journal of Nutrition, 93, S163-S168. http://dx.doi.org/10.1079/bjn20041339
Turnbaugh, P.J., Ley, R.E., Mahowald, M.A., Magrini, V., Mardis, E.R. and Gordon, J.I. (2006) An Obesity-Associated Gut Microbiome with Increased Capacity for Energy Harvest. Nature, 444, 1027-1031. http://dx.doi.org/10.1038/nature05414
Ley, R.E., Turnbaugh, P.J., Klein, S. and Gordon, J.I. (2006) Microbial Ecology: Human Gut Microbes Associated with Obesity. Nature, 444, 1022-1023. http://dx.doi.org/10.1038/4441022a
Bellino, F.L. and Wise, P.M. (2003) Nonhuman Primate Models of Menopause Workshop. Biology of Reproduction, 68, 10-18. http://dx.doi.org/10.1095/biolreprod.102.005215
Wood, C.E., Register, T.C., Franke, A.A., Anthony, M.S. and Cline, J.M. (2006) Dietary Soy Isoflavones Inhibit Estrogen Effects in the Postmenopausal Breast. Cancer Research, 66, 1241-1249. http://dx.doi.org/10.1158/0008-5472.CAN-05-2067
National Research Council (1996) Guide for the Care and Use of Laboratory Animals. National Academy Press. Washington DC.
Bayne, K. (1998) Developing Guidelines on the Care and Use of Animals. Annals of the New York Academy of Sciences, 862, 105-110. http://dx.doi.org/10.1111/j.1749-6632.1998.tb09122.x
Jeong, A.R., Nakamura, S. and Mitsunaga, F. (2008) Gene Expression Profile of Th1 and Th2 Cytokines and Their Receptors in Human and Nonhuman Primates. Journal of Medical Primatology, 37, 290-296. http://dx.doi.org/10.1111/j.1600-0684.2008.00289.x
Gabrielsson, B.G., Olofsson, L.E., Sjögren, A., Jernas, M., Elander, A., Lönn, M., et al. (2005) Evaluation of Reference Genes for Studies of Gene Expression in Human Adipose Tissue. Obesity Research, 13, 649-652. http://dx.doi.org/10.1038/oby.2005.72
Matsuzawa, T., Nomura, M. and Takashi, U. (1993) Clinical Pathology Reference Ranges of Laboratory Animals. The Journal of Veterinary Medical Science, 55, 351-362. http://dx.doi.org/10.1292/jvms.55.351
Bouhnik, Y., Raskine, L., Champion, K., Andrieux, C., Penven, S., Jacobs, H. and Simoneau, G. (2007) Prolonged Administration of Low-Dose Inulin Stimulates the Growth of Bifidobacteria in Humans. Nutrition Research, 27, 187-193. http://dx.doi.org/10.1016/j.nutres.2007.01.013
Harold, F.M. and Levin, E. (1974) Lactic Acid Translocation: Terminal Step in Glycolysis by Streptococcus faecalis. Journal of Bacteriology, 117, 1141-1148.
Quintanilha, A.G., Zilberstein, B., Santos, M.A., Pajecki, D., Moura, E.G., Alves, P.R., Maluf-Filho, F. and Cecconello, I. (2007) A Novel Sampling Method for the Investigation of Gut Microbiota. World Journal of Gastroenterology, 13, 3990-3995. http://dx.doi.org/10.3748/wjg.v13.i29.3990
Zilberstein, B., Quintanilha, A.G., Santos, M.A., Pajecki, D., Moura, E.G., Alves, P.R., MalufFilho, F., de Souza, J.A. and Gama-Rodrigues, J. (2007) Digestive Tract Microbiota in Healthy Volunteers. Clinics, 62, 47-54. http://dx.doi.org/10.1590/S1807-59322007000100008
Bhatti, M.A. and Frank, M.O. (2000) Veillonella parvula Meningitis: Case Report and Review of Veillonella Infections. Clinical Infectious Diseases, 31, 839-840. http://dx.doi.org/10.1086/314046
Hinton Jr., A. and Hume, M.E. (1995) Antibacterial Activity of the Metabolic By-Products of a Veillonella Species and Bacteroides fragilis. Anaerobe, 1, 121-127. http://dx.doi.org/10.1006/anae.1995.1007
Gibson, G.R. and Wang, X. (1994) Bifidogenic Properties of Different Types of Fructo-Oligosaccharides. Food Microbiology, 11, 491-498. http://dx.doi.org/10.1006/fmic.1994.1055
Van der Meulen, R., Makras, L., Verbrugghe, K., Adriany, T. and De Vuyst, L. (2006) In Vitro Kinetic Analysis of Oligofructose Consumption by Bacteroides and Bifidobacterium spp. Indicates Different Degradation Mechanisms. Applied and Environmental Microbiology, 72, 1006-1012. http://dx.doi.org/10.1128/AEM.72.2.1006-1012.2006
Egert, M., de Graaf, A.A., Maathuis, A., de Waard, P., Plugge, C.M., Smidt, H., Deutz, N.E.P., Dijkema, C., de Vos, W.M. and Venema, K. (2007) Identification of Glucose-fermenting Bacteria Present in an in vitro Model of the Human Intestine by RNA-stable Isotope Probing. FEMS Microbiology Ecology, 60, 126-135. http://dx.doi.org/10.1111/j.1574-6941.2007.00281.x
Cotter, P.D. and Hill, C. (2003) Surviving the Acid Test: Responses of Gram-positive Bacteria to Low pH. Microbiology and Molecular Biology Reviews, 67, 429-453. http://dx.doi.org/10.1128/MMBR.67.3.429-453.2003
Horton, J.D., Goldstein, J.L. and Brown, M.S. (2002) SREBPs: Activators of the Complete Program of Cholesterol and Fatty Acid Synthesis in the Liver. The Journal of Clinical Investigation, 109, 1125-1131. http://dx.doi.org/10.1172/JCI0215593
Korade, Z., Kenworthy, A.K. and Mirnics, K. (2009) Molecular Consequences of Altered Neuronal Cholesterol Biosynthesis. The Journal of Neuroscience Research, 87, 866-875. http://dx.doi.org/10.1002/jnr.21917
Liang, G., Yang, J., Horton, J.D., Hammer, R.E., Goldstein, J.L. and Brown, M.S. (2002) Diminished Hepatic Response to Fasting/Refeeding and Liver X Receptor Agonists in Mice with Selective Deficiency of Sterol Regulatory element-Binding Protein-1c.The Journal of Biological Chemistry, 277, 9520-9528. http://dx.doi.org/10.1074/jbc.M111421200
Koldamova, R., Fitz, N.F. and Lefterov, I. (2014) ATP-Binding Cassette Transporter A1: From Metabolism to Neurodegeneration. Neurobiology of Disease, 72, 13-21. http://dx.doi.org/10.1016/j.nbd.2014.05.007
Laffitte, B.A., Joseph, S.B., Chen, M., Castrillo, A., Repa, J., Wilpitz, D., Mangelsdorf, D. and Tontonoz, P. (2003) The Phospholipid Transfer Protein Gene Is a Liver X Receptor Target Expressed by Macrophages in Atherosclerotic Lesions. Molecular and Cellular Biology, 23, 2182-2191. http://dx.doi.org/10.1128/MCB.23.6.2182-2191.2003
Tangirala, R.K., Bischoff, E.D., Joseph, S.B., Wagner, B.L., Walczak, R., Laffitte, B.A., Daige, C.L., Thomas, D., Heyman, R.A., Mangelsdorf, D.J., Wang, X., Lusis, A.J., Tontonoz, P. and Schulman, I.G. (2002) Identification of Liver X Receptors as Macrophage Inhibitors of Atherosclerosis. Proceedings of the National Academy of Sciences of the United States of America, 99, 11896-11901. http://dx.doi.org/10.1073/pnas.182199799
Chen, L.N., Lyu, J., Yang, X.F., Ji, W.J., Yuan, B.X., Chen, M.X., Ma, X. and Wang, B. (2013) Liraglutide Ameliorates Glycometabolism and Insulin Resistance through the Upregulation of GLUT4 in Diabetic KKAy Mice. International Journal of Molecular Medicine, 32, 892-900.
Seki, S., Nakashima, H., Nakashima, M. and Kinoshita, M. (2011) Antitumor Immunity Produced by the Liver Kupffer Cells, NK Cells, NKT Cells, and CD8+ CD122+ T Cells. Clinical & Developmental Immunology, 2011, Article ID: 868345. http://dx.doi.org/10.1155/2011/868345
Flote, V.G., Furberg, A.S., McTiernan, A., Frydenberg, H., Ursin, G., Iversen, A., Lofteroed, T., Ellison, P.T., Wist, E.A., Egeland, T., Wilsgaard, T., Makar, K.W., Chang-Claude, J. and Thune, I. (2014) Gene Variations in OestrogenPathways, CYP19A1, Daily 17β-Estradiol and Mammographic Density Phenotypes in Premenopausal Women. Breast Cancer Research, 16, 499. http://dx.doi.org/10.1186/s13058-014-0499-2
Villeneuve, J.P. and Pichette, V. (2004) Cytochrome P450 and Liver Diseases. Current Drug Metabolism, 5, 273-282. http://dx.doi.org/10.2174/1389200043335531
Tan, J., McKenzie, C., Potamitis, M., Thorburn, A.N., Mackay, C.R. and Macia, L. (2014) The Role of Short-Chain Fatty Acids in Health and Disease. Advances in Immunology, 121, 91-119. http://dx.doi.org/10.1016/B978-0-12-800100-4.00003-9