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Research article

Molecular and Cellular Microbiology (MCM)  |  Pathogenesis and Host-Microbial interactions

Difference in the Gut Microbiome between Ovariectomy-Induced Obesity and Diet-Induced Obesity

Sungmi Choi 1, Yu-Jin Hwang 2, Min-Jeong Shin 1, 3 and Hana Yi 1, 3*

1Department of Public Health Sciences, Graduate School, Korea University, Seoul 02841, Republic of Korea, 2Department of Agrofood Resources, National Institute of Agricultural Science, RDA, Wanju 54875, Republic of Korea, 3School of Biosystem and Biomedical Science, Korea University, Seoul 02841, Republic of Korea

Received: October 10, 2017; Accepted: November 7, 2017

J. Microbiol. Biotechnol. 2017; 27(12): 2228-2236

Published December 28, 2017 https://doi.org/10.4014/jmb.1710.10001

Copyright © The Korean Society for Microbiology and Biotechnology.

Abstract

During menopausal transition, the imbalance of estrogen causes body weight gain. Although gut microbiome dysbiosis has been reported in postmenopausal obesity, it is not clear whether there is any difference in the microbiome profile between dietary-induced obesity and postmenopausal obesity. Therefore, in this study, we analyzed intestinal samples from ovariectomized mice and compared them with those of mice with high-fat diet-induced obesity. To further evaluate the presence of menopause-specific bacteria-gene interactions, we also analyzed the liver transcriptome. Investigation of the 16S rRNA V3-V4 region amplicon sequence profile revealed that menopausal obesity and dietary obesity resulted in similar gut microbiome structures. However, Bifidobacterium animalis was exclusively observed in the ovariectomized mice, which indicated that menopausal obesity resulted in a different intestinal microbiome than dietary obesity. Additionally, several bacterial taxa (Dorea species, Akkermansia muciniphila, and Desulfovibrio species) were found when the ovariectomized mice were treated with a high-fat diet. A significant correlation between the above-mentioned menopause-specific bacteria and the genes for female hormone metabolism was also observed, suggesting the possibility of bacteria-gene interactions in menopausal obesity. Our findings revealed the characteristics of the intestinal microbiome in menopausal obesity in the mouse model, which is very similar to the dietary obesity microbiome but having its own diagnostic bacteria.

Keywords

Microbiome, menopause, obesity, ovariectomy

References

  1. McKinlay SM, Brambilla DJ, Posner JG. 1992. The normal menopause transition. Maturitas 14: 103-115.
    CrossRef
  2. Eriksen EF, Colvard DS, Berg NJ, Graham ML, Mann KG, Spelsberg TC, et al. 1988. Evidence of estrogen receptors in normal human osteoblast-like cells. Science 241: 84-86.
    Pubmed CrossRef
  3. Lindsay R, Hart DM, Aitken JM, MacDonald EB, Anderson JB, Clarke AC. 1976. Long-term prevention of postmenopausal osteoporosis by oestrogen. Evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet 1: 1038-1041.
    CrossRef
  4. Riggs BL, Khosla S, Melton LJ 3rd. 1998. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J. Bone Miner. Res. 13: 763-773.
    Pubmed CrossRef
  5. Paganini-Hill A, Henderson VW. 1994. Estrogen deficiency and risk of Alzheimer’s disease in women. Am. J. Epidemiol. 140: 256-261.
    Pubmed CrossRef
  6. Yue X, Lu M, Lancaster T, Cao P, Honda S, Staufenbiel M, et al. 2005. Brain estrogen deficiency accelerates Aβ plaque formation in an Alzheimer’s disease animal model. Proc. Natl. Acad. Sci. USA 102: 19198-19203.
    Pubmed PMC CrossRef
  7. Ainslie DA, Morris MJ, Wittert G, Turnbull H, Proietto J, Thorburn AW. 2001. Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y. Int. J. Obes. Relat. Metab. Disord. 25: 1680-1688.
    Pubmed CrossRef
  8. Lovejoy JC, Champagne CM, d e Jonge L, X ie H , Smith SR. 2008. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int. J. Obes. 32: 949-958.
    Pubmed PMC CrossRef
  9. Shimizu H, Shimomura Y, Nakanishi Y, Futawatari T, Ohtani K, Sato N, et al. 1997. Estrogen increases in vivo leptin production in rats and human subjects. J. Endocrinol. 154: 285-292.
    Pubmed CrossRef
  10. Carr MC. 2003. The emergence of the metabolic syndrome with menopause. J. Clin. Endocrinol. Metab. 88: 2404-2411.
    Pubmed CrossRef
  11. Dosi R, Bhatt N, Shah P, Patell R. 2014. Cardiovascular disease and menopause. J. Clin. Diagn. Res. 8: 62-64.
  12. Hu FB, Grodstein F, Hennekens CH, Colditz GA, Johnson M, Manson JE, et al. 1999. Age at natural menopause and risk of cardiovascular disease. Arch. Intern. Med. 159: 1061-1066.
    Pubmed CrossRef
  13. Ramezani Tehrani F, Behboudi-Gandevani S, Ghanbarian A, Azizi F. 2014. Effect of menopause on cardiovascular disease and its risk factors: a 9-year follow-up study. Climacteric 17: 164-172.
    Pubmed CrossRef
  14. Coylewright M, Reckelhoff JF, Ouyang P. 2008. Menopause and hypertension: an age-old debate. Hypertension 51: 952-959.
    Pubmed CrossRef
  15. Rappelli A. 2 002. H y pertension a nd o besity after t he menopause. J. Hypertens. Suppl. 20: S26-S28.
    Pubmed
  16. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. 2002. Postmenopausal hormone replacement therapy: scientific review. JAMA 288: 872-881.
    Pubmed CrossRef
  17. Hummelen R, Macklaim JM, Bisanz JE, Hammond JA, McMillan A, Vongsa R, et al. 2011. Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. PLoS One 6: e26602.
    Pubmed PMC CrossRef
  18. Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, et al. 2014. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause 21: 450-458.
    Pubmed PMC CrossRef
  19. Cauci S, Driussi S, De Santo D, Penacchioni P, Iannicelli T, Lanzafame P, et al. 2002. Prevalence of bacterial vaginosis and vaginal flora changes in peri- and postmenopausal women. J. Clin. Microbiol. 40: 2147-2152.
    Pubmed PMC CrossRef
  20. Fuhrman BJ, Feigelson HS, Flores R, Gail MH, Xu X, Ravel J, et al. 2014. Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women. J. Clin. Endocrinol. Metab. 99: 4632-4640.
    Pubmed PMC CrossRef
  21. Flores R, Shi J, Fuhrman B, Xu X, Veenstra TD, Gail MH, et al. 2012. Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study. J. Transl. Med. 10: 253.
    Pubmed PMC CrossRef
  22. Menon R, Watson SE, Thomas LN, Allred CD, Dabney A, Azcarate-Peril MA, et al. 2013. Diet complexity and estrogen receptor beta status affect the composition of the murine intestinal microbiota. Appl. Environ. Microbiol. 79: 5763-5773.
    Pubmed PMC CrossRef
  23. Kwa M, Plottel CS, Blaser MJ, Adams S. 2016. The intestinal microbiome and estrogen receptor-positive female breast cancer. J. Natl. Cancer Inst. 108: djw029.
    Pubmed PMC
  24. Brahe L K, L e Chatelier E, P rifti E, P ons N, K ennedy S, Hansen T, et al. 2015. Specific gut microbiota features and metabolic markers in postmenopausal women with obesity. Nutr. Diabetes 5: e159.
    Pubmed PMC CrossRef
  25. Lawley B, Tannock GW. 2017. Analysis of 16S rRNA gene amplicon sequences using the QIIME software package. Methods Mol. Biol. 1537: 153-163.
    Pubmed CrossRef
  26. DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, et al. 2006. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl. Environ. Microbiol. 72: 5069-5072.
    Pubmed PMC CrossRef
  27. Edgar RC. 2010. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26: 2460-2461.
    Pubmed CrossRef
  28. Hamady M, Lozupone C, Knight R. 2010. Fast UniFrac:facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 4: 17-27.
    Pubmed PMC CrossRef
  29. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. 2011. Metagenomic biomarker discovery and explanation. Genome Biol. 12: R60.
    Pubmed PMC CrossRef
  30. Yoon SH, Ha SM, Kwon S, Lim J, Kim Y, Seo H, et al. 2017. Introducing EzBioCloud: a taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies. Int. J. Syst. Evol. Microbiol. 67: 1613-1617.
    Pubmed CrossRef
  31. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. 2000. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25: 25-29.
    Pubmed PMC CrossRef
  32. Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. 2017. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 45: D353-D361.
    Pubmed PMC CrossRef
  33. The R project for statistical computing. Available from http://www.r-project.org. Accessed 18 September 2017.
  34. Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C, et al. 2007. Integration of biological networks and gene expression data using Cytoscape. Nat. Protoc. 2: 2366-2382.
    Pubmed PMC CrossRef
  35. Cox-York KA, Sheflin AM, Foster MT, Gentile CL, Kahl A, Koch LG, et al. 2015. Ovariectomy results in differential shifts in gut microbiota in low versus high aerobic capacity rats. Physiol. Rep. 3: e12488.
    Pubmed PMC CrossRef
  36. Keenan MJ, Janes M, Robert J, Martin RJ, Raggio AM, McCutcheon KL, et al. 2013. Resistant starch from high amy lose m aize (HAM-RS2) r educes body fat a nd i ncreases gut bacteria in ovariectomized (OVX) rats. Obesity 21: 981-984.
    Pubmed PMC CrossRef
  37. Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, et al. 2009. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137: 1716-1724.e1-2.
  38. Turnbaugh PJ, Baeckhed F, Fulton L, Gordon JI. 2008. Dietinduced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3: 213-223.
    Pubmed PMC CrossRef
  39. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. 2011. Linking long-term dietary patterns with gut microbial enterotypes. Science 334: 105-108.
    Pubmed PMC CrossRef
  40. Rabot S, Membrez M, Blancher F, Berger B, Moine D, Krause L, et al. 2016. High fat diet drives obesity regardless the composition of gut microbiota in mice. Sci. Rep. 6: 32484.
    Pubmed PMC CrossRef
  41. Liu TW, Park YM, Holscher HD, Padilla J, Scroggins RJ, Welly R, et al. 2015. Physical activity differentially affects the cecal microbiota of ovariectomized female rats selectively bred for high and low aerobic capacity. PLoS One 10: e0136150.
    Pubmed PMC CrossRef
  42. Krebs CJ, Jarvis ED, Pfaff DW. 1999. The 70-kDa heat shock cognate protein (Hsc73) gene is enhanced by ovarian hormones in the ventromedial hypothalamus. Proc. Natl. Acad. Sci. USA 96: 1686-1691.
    Pubmed PMC CrossRef
  43. Sarvari M, Kallo I, Hrabovszky E, Solymosi N, Liposits Z. 2014. Ovariectomy and subsequent treatment with estrogen receptor agonists tune the innate immune system of the hippocampus in middle-aged female rats. PLoS One 9: e88540.
    Pubmed PMC CrossRef
  44. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, et al. 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA 110: 9066-9071.
    Pubmed PMC CrossRef
  45. Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS, et al. 2014. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63: 727-735.
    Pubmed CrossRef

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Article

Research article

J. Microbiol. Biotechnol. 2017; 27(12): 2228-2236

Published online December 28, 2017 https://doi.org/10.4014/jmb.1710.10001

Copyright © The Korean Society for Microbiology and Biotechnology.

Difference in the Gut Microbiome between Ovariectomy-Induced Obesity and Diet-Induced Obesity

Sungmi Choi 1, Yu-Jin Hwang 2, Min-Jeong Shin 1, 3 and Hana Yi 1, 3*

1Department of Public Health Sciences, Graduate School, Korea University, Seoul 02841, Republic of Korea, 2Department of Agrofood Resources, National Institute of Agricultural Science, RDA, Wanju 54875, Republic of Korea, 3School of Biosystem and Biomedical Science, Korea University, Seoul 02841, Republic of Korea

Received: October 10, 2017; Accepted: November 7, 2017

Abstract

During menopausal transition, the imbalance of estrogen causes body weight gain. Although
gut microbiome dysbiosis has been reported in postmenopausal obesity, it is not clear whether
there is any difference in the microbiome profile between dietary-induced obesity and
postmenopausal obesity. Therefore, in this study, we analyzed intestinal samples from
ovariectomized mice and compared them with those of mice with high-fat diet-induced
obesity. To further evaluate the presence of menopause-specific bacteria-gene interactions, we
also analyzed the liver transcriptome. Investigation of the 16S rRNA V3-V4 region amplicon
sequence profile revealed that menopausal obesity and dietary obesity resulted in similar gut
microbiome structures. However, Bifidobacterium animalis was exclusively observed in the
ovariectomized mice, which indicated that menopausal obesity resulted in a different
intestinal microbiome than dietary obesity. Additionally, several bacterial taxa (Dorea species,
Akkermansia muciniphila, and Desulfovibrio species) were found when the ovariectomized mice
were treated with a high-fat diet. A significant correlation between the above-mentioned
menopause-specific bacteria and the genes for female hormone metabolism was also observed,
suggesting the possibility of bacteria-gene interactions in menopausal obesity. Our findings
revealed the characteristics of the intestinal microbiome in menopausal obesity in the mouse
model, which is very similar to the dietary obesity microbiome but having its own diagnostic
bacteria.

Keywords: Microbiome, menopause, obesity, ovariectomy

References

  1. McKinlay SM, Brambilla DJ, Posner JG. 1992. The normal menopause transition. Maturitas 14: 103-115.
    CrossRef
  2. Eriksen EF, Colvard DS, Berg NJ, Graham ML, Mann KG, Spelsberg TC, et al. 1988. Evidence of estrogen receptors in normal human osteoblast-like cells. Science 241: 84-86.
    Pubmed CrossRef
  3. Lindsay R, Hart DM, Aitken JM, MacDonald EB, Anderson JB, Clarke AC. 1976. Long-term prevention of postmenopausal osteoporosis by oestrogen. Evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet 1: 1038-1041.
    CrossRef
  4. Riggs BL, Khosla S, Melton LJ 3rd. 1998. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J. Bone Miner. Res. 13: 763-773.
    Pubmed CrossRef
  5. Paganini-Hill A, Henderson VW. 1994. Estrogen deficiency and risk of Alzheimer’s disease in women. Am. J. Epidemiol. 140: 256-261.
    Pubmed CrossRef
  6. Yue X, Lu M, Lancaster T, Cao P, Honda S, Staufenbiel M, et al. 2005. Brain estrogen deficiency accelerates Aβ plaque formation in an Alzheimer’s disease animal model. Proc. Natl. Acad. Sci. USA 102: 19198-19203.
    Pubmed KoreaMed CrossRef
  7. Ainslie DA, Morris MJ, Wittert G, Turnbull H, Proietto J, Thorburn AW. 2001. Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y. Int. J. Obes. Relat. Metab. Disord. 25: 1680-1688.
    Pubmed CrossRef
  8. Lovejoy JC, Champagne CM, d e Jonge L, X ie H , Smith SR. 2008. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int. J. Obes. 32: 949-958.
    Pubmed KoreaMed CrossRef
  9. Shimizu H, Shimomura Y, Nakanishi Y, Futawatari T, Ohtani K, Sato N, et al. 1997. Estrogen increases in vivo leptin production in rats and human subjects. J. Endocrinol. 154: 285-292.
    Pubmed CrossRef
  10. Carr MC. 2003. The emergence of the metabolic syndrome with menopause. J. Clin. Endocrinol. Metab. 88: 2404-2411.
    Pubmed CrossRef
  11. Dosi R, Bhatt N, Shah P, Patell R. 2014. Cardiovascular disease and menopause. J. Clin. Diagn. Res. 8: 62-64.
  12. Hu FB, Grodstein F, Hennekens CH, Colditz GA, Johnson M, Manson JE, et al. 1999. Age at natural menopause and risk of cardiovascular disease. Arch. Intern. Med. 159: 1061-1066.
    Pubmed CrossRef
  13. Ramezani Tehrani F, Behboudi-Gandevani S, Ghanbarian A, Azizi F. 2014. Effect of menopause on cardiovascular disease and its risk factors: a 9-year follow-up study. Climacteric 17: 164-172.
    Pubmed CrossRef
  14. Coylewright M, Reckelhoff JF, Ouyang P. 2008. Menopause and hypertension: an age-old debate. Hypertension 51: 952-959.
    Pubmed CrossRef
  15. Rappelli A. 2 002. H y pertension a nd o besity after t he menopause. J. Hypertens. Suppl. 20: S26-S28.
    Pubmed
  16. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. 2002. Postmenopausal hormone replacement therapy: scientific review. JAMA 288: 872-881.
    Pubmed CrossRef
  17. Hummelen R, Macklaim JM, Bisanz JE, Hammond JA, McMillan A, Vongsa R, et al. 2011. Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. PLoS One 6: e26602.
    Pubmed KoreaMed CrossRef
  18. Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, et al. 2014. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause 21: 450-458.
    Pubmed KoreaMed CrossRef
  19. Cauci S, Driussi S, De Santo D, Penacchioni P, Iannicelli T, Lanzafame P, et al. 2002. Prevalence of bacterial vaginosis and vaginal flora changes in peri- and postmenopausal women. J. Clin. Microbiol. 40: 2147-2152.
    Pubmed KoreaMed CrossRef
  20. Fuhrman BJ, Feigelson HS, Flores R, Gail MH, Xu X, Ravel J, et al. 2014. Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women. J. Clin. Endocrinol. Metab. 99: 4632-4640.
    Pubmed KoreaMed CrossRef
  21. Flores R, Shi J, Fuhrman B, Xu X, Veenstra TD, Gail MH, et al. 2012. Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study. J. Transl. Med. 10: 253.
    Pubmed KoreaMed CrossRef
  22. Menon R, Watson SE, Thomas LN, Allred CD, Dabney A, Azcarate-Peril MA, et al. 2013. Diet complexity and estrogen receptor beta status affect the composition of the murine intestinal microbiota. Appl. Environ. Microbiol. 79: 5763-5773.
    Pubmed KoreaMed CrossRef
  23. Kwa M, Plottel CS, Blaser MJ, Adams S. 2016. The intestinal microbiome and estrogen receptor-positive female breast cancer. J. Natl. Cancer Inst. 108: djw029.
    Pubmed KoreaMed
  24. Brahe L K, L e Chatelier E, P rifti E, P ons N, K ennedy S, Hansen T, et al. 2015. Specific gut microbiota features and metabolic markers in postmenopausal women with obesity. Nutr. Diabetes 5: e159.
    Pubmed KoreaMed CrossRef
  25. Lawley B, Tannock GW. 2017. Analysis of 16S rRNA gene amplicon sequences using the QIIME software package. Methods Mol. Biol. 1537: 153-163.
    Pubmed CrossRef
  26. DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, et al. 2006. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl. Environ. Microbiol. 72: 5069-5072.
    Pubmed KoreaMed CrossRef
  27. Edgar RC. 2010. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26: 2460-2461.
    Pubmed CrossRef
  28. Hamady M, Lozupone C, Knight R. 2010. Fast UniFrac:facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 4: 17-27.
    Pubmed KoreaMed CrossRef
  29. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. 2011. Metagenomic biomarker discovery and explanation. Genome Biol. 12: R60.
    Pubmed KoreaMed CrossRef
  30. Yoon SH, Ha SM, Kwon S, Lim J, Kim Y, Seo H, et al. 2017. Introducing EzBioCloud: a taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies. Int. J. Syst. Evol. Microbiol. 67: 1613-1617.
    Pubmed CrossRef
  31. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. 2000. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25: 25-29.
    Pubmed KoreaMed CrossRef
  32. Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. 2017. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 45: D353-D361.
    Pubmed KoreaMed CrossRef
  33. The R project for statistical computing. Available from http://www.r-project.org. Accessed 18 September 2017.
  34. Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C, et al. 2007. Integration of biological networks and gene expression data using Cytoscape. Nat. Protoc. 2: 2366-2382.
    Pubmed KoreaMed CrossRef
  35. Cox-York KA, Sheflin AM, Foster MT, Gentile CL, Kahl A, Koch LG, et al. 2015. Ovariectomy results in differential shifts in gut microbiota in low versus high aerobic capacity rats. Physiol. Rep. 3: e12488.
    Pubmed KoreaMed CrossRef
  36. Keenan MJ, Janes M, Robert J, Martin RJ, Raggio AM, McCutcheon KL, et al. 2013. Resistant starch from high amy lose m aize (HAM-RS2) r educes body fat a nd i ncreases gut bacteria in ovariectomized (OVX) rats. Obesity 21: 981-984.
    Pubmed KoreaMed CrossRef
  37. Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, et al. 2009. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137: 1716-1724.e1-2.
  38. Turnbaugh PJ, Baeckhed F, Fulton L, Gordon JI. 2008. Dietinduced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3: 213-223.
    Pubmed KoreaMed CrossRef
  39. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. 2011. Linking long-term dietary patterns with gut microbial enterotypes. Science 334: 105-108.
    Pubmed KoreaMed CrossRef
  40. Rabot S, Membrez M, Blancher F, Berger B, Moine D, Krause L, et al. 2016. High fat diet drives obesity regardless the composition of gut microbiota in mice. Sci. Rep. 6: 32484.
    Pubmed KoreaMed CrossRef
  41. Liu TW, Park YM, Holscher HD, Padilla J, Scroggins RJ, Welly R, et al. 2015. Physical activity differentially affects the cecal microbiota of ovariectomized female rats selectively bred for high and low aerobic capacity. PLoS One 10: e0136150.
    Pubmed KoreaMed CrossRef
  42. Krebs CJ, Jarvis ED, Pfaff DW. 1999. The 70-kDa heat shock cognate protein (Hsc73) gene is enhanced by ovarian hormones in the ventromedial hypothalamus. Proc. Natl. Acad. Sci. USA 96: 1686-1691.
    Pubmed KoreaMed CrossRef
  43. Sarvari M, Kallo I, Hrabovszky E, Solymosi N, Liposits Z. 2014. Ovariectomy and subsequent treatment with estrogen receptor agonists tune the innate immune system of the hippocampus in middle-aged female rats. PLoS One 9: e88540.
    Pubmed KoreaMed CrossRef
  44. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, et al. 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA 110: 9066-9071.
    Pubmed KoreaMed CrossRef
  45. Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS, et al. 2014. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63: 727-735.
    Pubmed CrossRef