Gender Differences in the Gut Microbiome and How These Affect Cardiovascular Diseases

  • Adriana Cabal
  • Trudy M. Wassenaar
  • David W. UsseryEmail author


The literature was reviewed to search for consistently reported differences in the gut microbiome between females and males, in an attempt to relate such changes to different risks of cardiovascular disease that exist between the genders. Although multiple publications were identified that reported gender differences in the gut microbiome, none of the described observations were consistent. Apparently, the variation in gut microbiome between populations under study, as a result of differences in geography, life style, diet, age, genetics and possible other factors is more extensive than the variation between males and females. However, we summarize a number of findings on gender differences reported for cardiovascular diseases that may have a link to the microbiome, for instance the presence of irritable bowel disease which is a risk factor for cardiovascular disease, coincides with a dysbiosis of the gut microbiome, and is more common in females than males. Other microbiome-related gender differences may pose a greater risk for males, so that, overall, there is no known positive or negative generally applicable effect of a ‘female-type’ or ‘male-type’ microbiome that would have a significant effect on risk or severity of cardiovascular diseases.


Gut microbiome 16S rRNA Gender differences Irritable bowel disease 



We thank Linda J. Larson-Prior for stimulating discussions. This work was funded in part by the Arkansas Research Alliance and the Helen Adams & Arkansas Research Alliance Professor & Chair.


  1. 1.
    Hollister EB, Gao C, Versalovic J. Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology. 2014;146(6):1449–58. Scholar
  2. 2.
    Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science (New York, NY). 2005;308(5728):1635–8. Scholar
  3. 3.
    Quigley EMM. Gut bacteria in health and disease. Gastroenterol Hepatol. 2013;9(9):560–9.Google Scholar
  4. 4.
    Dominianni C, Sinha R, Goedert JJ, Pei Z, Yang L, Hayes RB, Ahn J. Sex, body mass index, and dietary fiber intake influence the human gut microbiome. PLoS One. 2015;10(4):e0124599. Scholar
  5. 5.
    Li M, Wang B, Zhang M, Rantalainen M, Wang S, Zhou H, Zhang Y, Shen J, Pang X, Zhang M, Wei H, Chen Y, Lu H, Zuo J, Su M, Qiu Y, Jia W, Xiao C, Smith LM, Yang S, Holmes E, Tang H, Zhao G, Nicholson JK, Li L, Zhao L. Symbiotic gut microbes modulate human metabolic phenotypes. Proc Natl Acad Sci U S A. 2008;105(6):2117–22. Scholar
  6. 6.
    Mueller S, Saunier K, Hanisch C, Norin E, Alm L, Midtvedt T, Cresci A, Silvi S, Orpianesi C, Verdenelli MC, Clavel T, Koebnick C, Zunft H-JF, Doré J, Blaut M. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl Environ Microbiol. 2006;72(2):1027–33.
  7. 7.
    Haro C, Rangel-Zúñiga OA, Alcalá-Díaz JF, Gómez-Delgado F, Pérez-Martínez P, Delgado-Lista J, Quintana-Navarro GM, Landa BB, Navas-Cortés JA, Tena-Sempere M, Clemente JC, López-Miranda J, Pérez-Jiménez F, Camargo A. Intestinal microbiota is influenced by gender and body mass index. PLoS One. 2016;11(5):e0154090. Scholar
  8. 8.
    Schnorr SL, Candela M, Rampelli S, Centanni M, Consolandi C, Basaglia G, Turroni S, Biagi E, Peano C, Severgnini M, Fiori J, Gotti R, De Bellis G, Luiselli D, Brigidi P, Mabulla A, Marlowe F, Henry AG, Crittenden AN. Gut microbiome of the Hadza hunter-gatherers. Nat Commun. 2014;5:3654. Scholar
  9. 9.
    Triantafyllou K, Chang C, Pimentel M. Methanogens, methane and gastrointestinal motility. J Neurogastroenterol Motil. 2014;20(1):31–40. Scholar
  10. 10.
    Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto J-M, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Doré J, Meta HITC, Weissenbach J, Ehrlich SD, Bork P. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–80. Scholar
  11. 11.
    Liang C, Tseng H-C, Chen H-M, Wang W-C, Chiu C-M, Chang J-Y, K-Y L, Weng S-L, Chang T-H, Chang C-H, Weng C-T, Wang H-M, Huang H-D. Diversity and enterotype in gut bacterial community of adults in Taiwan. BMC Genomics. 2017;18(Suppl 1):932. Scholar
  12. 12.
    Ding T, Schloss PD. Dynamics and associations of microbial community types across the human body. Nature. 2014;509(7500):357–60. Scholar
  13. 13.
    Aagaard K, Petrosino J, Keitel W, Watson M, Katancik J, Garcia N, Patel S, Cutting M, Madden T, Hamilton H, Harris E, Gevers D, Simone G, McInnes P, Versalovic J. The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters. FASEB J. 2013;27(3):1012–22. Scholar
  14. 14.
    Kovacs A, Ben-Jacob N, Tayem H, Halperin E, Iraqi FA, Gophna U. Genotype is a stronger determinant than sex of the mouse gut microbiota. Microb Ecol. 2011;61(2):423–8. Scholar
  15. 15.
    Voreades N, Kozil A, Weir TL. Diet and the development of the human intestinal microbiome. Front Microbiol. 2014;5:494. Scholar
  16. 16.
    Suzuki Y, Ikeda K, Sakuma K, Kawai S, Sawaki K, Asahara T, Takahashi T, Tsuji H, Nomoto K, Nagpal R, Wang C, Nagata S, Yamashiro Y. Association between yogurt consumption and intestinal microbiota in healthy young adults differs by host gender. Front Microbiol. 2017;8:847. Scholar
  17. 17.
    The Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14. Scholar
  18. 18.
    Escobar JS, Klotz B, Valdes BE, Agudelo GM. The gut microbiota of Colombians differs from that of Americans, Europeans and Asians. BMC Microbiol. 2014;14(1):311. Scholar
  19. 19.
    Kurokawa K, Itoh T, Kuwahara T, Oshima K, Toh H, Toyoda A, Takami H, Morita H, Sharma VK, Srivastava TP, Taylor TD, Noguchi H, Mori H, Ogura Y, Ehrlich DS, Itoh K, Takagi T, Sakaki Y, Hayashi T, Hattori M. Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes. DNA Res. 2007;14(4):169–81. Scholar
  20. 20.
    Wallis A, Butt H, Ball M, Lewis DP, Bruck D. Support for the microgenderome: associations in a human clinical population. Sci Rep. 2016;6:19171. Scholar
  21. 21.
    de Moraes AC, Fernandes GR, da Silva IT, Almeida-Pititto B, Gomes EP, Pereira AD, Ferreira SR. Enterotype may drive the dietary-associated cardiometabolic risk factors. Front Cell Infect Microbiol. 2017;7:47. Scholar
  22. 22.
    Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G, Wu S, Liu W, Cui Q, Geng B, Zhang W, Weldon R, Auguste K, Yang L, Liu X, Chen L, Yang X, Zhu B, Cai J. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017;5:14. Scholar
  23. 23.
    Singh RK, Chang H-W, Yan D, Lee KM, Ucmak D, Wong K, Abrouk M, Farahnik B, Nakamura M, Zhu TH, Bhutani T, Liao W. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15:73. Scholar
  24. 24.
    Tang WH, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res. 2017;120(7):1183–96. Scholar
  25. 25.
    Sonnenburg JL, Backhed F. Diet-microbiota interactions as moderators of human metabolism. Nature. 2016;535(7610):56–64. Scholar
  26. 26.
    Khan MJ, Gerasimidis K, Edwards CA, Shaikh MG. Role of gut microbiota in the aetiology of obesity: proposed mechanisms and review of the literature. J Obes. 2016;2016:7353642. Scholar
  27. 27.
    Fu J, Bonder MJ, Cenit MC, Tigchelaar EF, Maatman A, Dekens JAM, Brandsma E, Marczynska J, Imhann F, Weersma RK, Franke L, Poon TW, Xavier RJ, Gevers D, Hofker MH, Wijmenga C, Zhernakova A. The gut microbiome contributes to a substantial proportion of the variation in blood lipids. Circ Res. 2015;117(9):817–24.
  28. 28.
    Most J, Goossens GH, Reijnders D, Canfora EE, Penders J, Blaak EE. Gut microbiota composition strongly correlates to peripheral insulin sensitivity in obese men but not in women. Benefic Microbes. 2017;8(4):557–62. Scholar
  29. 29.
    Pevsner-Fischer M, Blacher E, Tatirovsky E, Ben-Dov IZ, Elinav E. The gut microbiome and hypertension. Curr Opin Nephrol Hypertens. 2017;26(1):1–8. Scholar
  30. 30.
    Cui L, Zhao T, Hu H, Zhang W, Hua X. Association Study of Gut Flora in Coronary Heart Disease through High-Throughput Sequencing. Biomed Res Int. 2017;2017:3796359. Scholar
  31. 31.
    Emoto T, Yamashita T, Sasaki N, Hirota Y, Hayashi T, So A, Kasahara K, Yodoi K, Matsumoto T, Mizoguchi T, Ogawa W, Hirata K. Analysis of gut microbiota in coronary artery disease patients: a possible link between gut microbiota and coronary artery disease. J Atheroscler Thromb. 2016;23(8):908–21. Scholar
  32. 32.
    Yamashita T, Emoto T, Sasaki N, Hirata K-i. Gut microbiota and coronary artery disease. Int Heart J. 2016;57(6):663–71. Scholar
  33. 33.
    Kelly TN, Bazzano LA, Ajami NJ, He H, Zhao J, Petrosino JF, Correa A, He J. Gut microbiome associates with lifetime cardiovascular disease risk profile among bogalusa heart study participants. Circ Res. 2016;119(8):956.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ussher JR, Lopaschuk GD, Arduini A. Gut microbiota metabolism of L-carnitine and cardiovascular risk. Atherosclerosis. 2013;231(2):456–61. Scholar
  35. 35.
    Yin J, Liao SX, He Y, Wang S, Xia GH, Liu FT, Zhu JJ, You C, Chen Q, Zhou L, Pan SY, Zhou HW. Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack. J Am Heart Assoc. 2015;4(11):pii: e002699. Scholar
  36. 36.
    Griffin JL, Wang X, Stanley E. Does our gut microbiome predict cardiovascular risk? A review of the evidence from metabolomics. Circ Cardiovasc Genetics. 2015;8(1):187–91. Scholar
  37. 37.
    Tang WH, Hazen SL. Microbiome, trimethylamine N-oxide, and cardiometabolic disease. Transl Res. 2017;179:108–15. Scholar
  38. 38.
    Kitai T, Kirsop J, Tang WH. Exploring the microbiome in heart failure. Curr Heart Fail Rep. 2016;13(2):103–9. Scholar
  39. 39.
    Tang WH, Hazen SL. The contributory role of gut microbiota in cardiovascular disease. J Clin Invest. 2014;124(10):4204–11. Scholar
  40. 40.
    Miller CA, Corbin KD, da Costa KA, Zhang S, Zhao X, Galanko JA, Blevins T, Bennett BJ, O’Connor A, Zeisel SH. Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study. Am J Clin Nutr. 2014;100(3):778–86. Scholar
  41. 41.
    Cho CE, Taesuwan S, Malysheva OV, Bender E, Tulchinsky NF, Yan J, Sutter JL, Caudill MA. Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: a randomized controlled trial. Mol Nutr Food Res. 2017;61(1).
  42. 42.
    Senthong V, Li XS, Hudec T, Coughlin J, Wu Y, Levison B, Wang Z, Hazen SL, Tang WH. Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with atherosclerotic burden. J Am Coll Cardiol. 2016a;67(22):2620–8. Scholar
  43. 43.
    Senthong V, Wang Z, Fan Y, Wu Y, Hazen SL, Tang WH. Trimethylamine N-oxide and mortality risk in patients with peripheral artery disease. J Am Heart Assoc. 2016;5(10):e004237. Scholar
  44. 44.
    Troseid M, Ueland T, Hov JR, Svardal A, Gregersen I, Dahl CP, Aakhus S, Gude E, Bjorndal B, Halvorsen B, Karlsen TH, Aukrust P, Gullestad L, Berge RK, Yndestad A. Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J Intern Med. 2015;277(6):717–26. Scholar
  45. 45.
    Tang WH, Wang Z, Fan Y, Levison B, Hazen JE, Donahue LM, Wu Y, Hazen SL. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014;64(18):1908–14. Scholar
  46. 46.
    Wang Z, Tang WH, Buffa JA, Fu X, Britt EB, Koeth RA, Levison BS, Fan Y, Wu Y, Hazen SL. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J. 2014;35(14):904–10. Scholar
  47. 47.
    Mafune A, Iwamoto T, Tsutsumi Y, Nakashima A, Yamamoto I, Yokoyama K, Yokoo T, Urashima M. Associations among serum trimethylamine-N-oxide (TMAO) levels, kidney function and infarcted coronary artery number in patients undergoing cardiovascular surgery: a cross-sectional study. Clin Exp Nephrol. 2016;20(5):731–9. Scholar
  48. 48.
    Senthong V, Wang Z, Li XS, Fan Y, Wu Y, Tang WH, Hazen SL. Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a COURAGE-like patient cohort. J Am Heart Assoc. 2016;5(6):pii: e002816. Scholar
  49. 49.
    Tang WH, Wang Z, Shrestha K, Borowski AG, Wu Y, Troughton RW, Klein AL, Hazen SL. Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure. J Card Fail. 2015;21(2):91–6. Scholar
  50. 50.
    Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, Li L, Fu X, Wu Y, Mehrabian M, Sartor RB, McIntyre TM, Silverstein RL, Tang WH, DiDonato JA, Brown JM, Lusis AJ, Hazen SL. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell. 2016;165(1):111–24. Scholar
  51. 51.
    Koupenova M, Mick E, Mikhalev E, Benjamin EJ, Tanriverdi K, Freedman JE. Sex differences in platelet toll-like receptors and their association with cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2015;35(4):1030–7. Scholar
  52. 52.
    Organ CL, Otsuka H, Bhushan S, Wang Z, Bradley J, Trivedi R, Polhemus DJ, Tang WH, Wu Y, Hazen SL, Lefer DJ. Choline diet and its gut microbe-derived metabolite, trimethylamine N-oxide, exacerbate pressure overload-induced heart failure. Circ Heart Fail. 2016;9(1):e002314. Scholar
  53. 53.
    Cheng S, Shah SH, Corwin EJ, Fiehn O, Fitzgerald RL, Gerszten RE, Illig T, Rhee EP, Srinivas PR, Wang TJ, Jain M. Potential impact and study considerations of metabolomics in cardiovascular health and disease: a scientific statement from the American Heart Association. Circ Cardiovasc Genet. 2017;10(2):pii: e000032. Scholar
  54. 54.
    Fiorucci S, Zampella A, Cirino G, Bucci M, Distrutti E. Decoding the vasoregulatory activities of bile acid-activated receptors in systemic and portal circulation: role of gaseous mediators. Am J Phys Heart Circ Phys. 2017;312(1):H21–h32. Scholar
  55. 55.
    Duboc H, Rainteau D, Rajca S, Humbert L, Farabos D, Maubert M, Grondin V, Jouet P, Bouhassira D, Seksik P, Sokol H, Coffin B, Sabate JM. Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24(6):513–520., e246-517. Scholar
  56. 56.
    Klem F, Wadhwa A, Prokop LJ, Sundt WJ, Farrugia G, Camilleri M, Singh S, Grover M. Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: a systematic review and meta-analysis. Gastroenterology. 2017;152(5):1042–1054.e1041. Scholar
  57. 57.
    Rogler G, Rosano G. The heart and the gut. Eur Heart J. 2014;35(7):426–30. Scholar
  58. 58.
    Zabell A, Tang WH. Targeting the microbiome in heart failure. Curr Treat Options Cardiovasc Med. 2017;19(4):27. Scholar
  59. 59.
    Kallio KA, Hätönen KA, Lehto M, Salomaa V, Mannisto S, Pussinen PJ. Endotoxemia, nutrition, and cardiometabolic disorders. Acta Diabetol. 2015;52(2):395–404.
  60. 60.
    Piya MK, Harte AL, McTernan PG. Metabolic endotoxaemia: is it more than just a gut feeling? Curr Opin Lipidol. 2013;24(1):78–85. Scholar
  61. 61.
    Manukyan MC, Weil BR, Wang Y, Abarbanell AM, Herrmann JL, Poynter JA, Brewster BD, Meldrum DR. Female stem cells are superior to males in preserving myocardial function following endotoxemia. Am J Physiol Regul Integr Comp Physiol. 2011;300(6):R1506–14. Scholar
  62. 62.
    Pasini E, Aquilani R, Testa C, Baiardi P, Angioletti S, Boschi F, Verri M, Dioguardi F. Pathogenic gut flora in patients with chronic heart failure. JACC Heart Fail. 2016;4:220–7. Scholar
  63. 63.
    Friedman CR, Neimann J, Wegener HC, Tauxe RV. Epidemiology of Campylobacter jejuni infections in the United States and other industrialized nations. In: Nachamkin I, Blaser MJ, editors. Campylobacter, vol II/6. Washington, DC: ASM International; 2000. p. 121–38.Google Scholar
  64. 64.
    Liljestrand JM, Paju S, Buhlin K, Persson RG, Sarna S, Nieminen MS, Sinisalo J, Mantyla P, Pussinen PJ. Lipopolysaccharide, a possible molecular mediator between periodontitis and coronary artery disease. J Clin Periodontol. 2017;44(8):784–92. Scholar
  65. 65.
    Hyvarinen K, Salminen A, Salomaa V, Pussinen PJ. Systemic exposure to a common periodontal pathogen and missing teeth are associated with metabolic syndrome. Acta Diabetol. 2015;52:179–82. Scholar
  66. 66.
    Player MS, Arch G, Mainous I, Everett CJ, Diaz VA, Knoll ME, Wright RU. Chlamydia pneumoniae and progression of subclinical atherosclerosis. Eur J Prev Cardiol. 2014;21(5):559–65.
  67. 67.
    Laek B, Szklo M, McClelland RL, Ding J, Tsai MY, Bluemke DA, Tracy R, Matsushita K. The prospective association of Chlamydia pneumoniae and four other pathogens with development of coronary artery calcium: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2013;230(2):268–74. CrossRefPubMedGoogle Scholar
  68. 68.
    Lajunen T, Bloigu A, Paldanius M, Pouta A, Laitinen J, Ruokonen A, Hartikainen AL, Savolainen M, Herzig KH, Leinonen M, Saikku P, Järvelin MR. The association of body mass index, waist and hip circumference, and waist-hip ratio with Chlamydia pneumoniae IgG antibodies and high-sensitive C-reactive protein at 31 years of age in Northern Finland Birth Cohort 1966. Int J Obes. 2011;35(12):1470–8.Google Scholar
  69. 69.
    Ibrahim A, Morais S, Ferro A, Lunet N, Peleteiro B. Sex-differences in the prevalence of Helicobacter pylori infection in pediatric and adult populations: systematic review and meta-analysis of 244 studies. Dig Liver Dis. 2017;49(7):742–9.

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Adriana Cabal
    • 1
  • Trudy M. Wassenaar
    • 1
    • 2
  • David W. Ussery
    • 2
    • 3
    Email author
  1. 1.Molecular Microbiology and Genomics ConsultantsZotzenheimGermany
  2. 2.Department of Biomedical InformaticsUniversity of Arkansas for Medical SciencesLittle RockUSA
  3. 3.Arkansas Center for Genomic Epidemiology and MedicineUniversity of Arkansas for Medical SciencesLittle RockUSA

Personalised recommendations