Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

You are viewing this page in draft mode.

The seminal microbiome in health and disease

Abstract

Owing to the fact that there are more microbial than human cells in our body and that humans contain more microbial than human genes, the microbiome has huge potential to influence human physiology, both in health and in disease. The use of next-generation sequencing technologies has helped to elucidate functional, quantitative and mechanistic aspects of the complex microorganism–host interactions that underlie human physiology and pathophysiology. The microbiome of semen is a field of increasing scientific interest, although this microbial niche is currently understudied compared with other areas of microbiome research. However, emerging evidence is beginning to indicate that the seminal microbiome has important implications for the reproductive health of men, the health of the couple and even the health of offspring, owing to transfer of microorganisms to the partner and offspring. As this field expands, further carefully designed and well-powered studies are required to unravel the true nature and role of the seminal microbiome.

Key points

  • Semen has a unique microbiome; however, its origin and function need to be further investigated in order to understand its role in health and disease.

  • Alterations in the bacterial composition of semen have been linked to a variety of disorders, including subinfertility and poor semen quality, prostatitis and HIV infection.

  • The seminal microbiome might influence a couple’s health and even that of their offspring, as well as affecting pregnancy outcomes.

  • When studying the male seminal microbiome, the partner’s reproductive tract microbiome and the sexual behaviours of both partners should also be considered.

  • Study of the seminal microbiome is still in its infancy, and further well-designed, large-cohort, functional studies are required.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Effects of the seminal microbiome on the male, the couple and their offspring.
Fig. 2: Population and lifestyle factors affecting the seminal microbiome.
Fig. 3: Bacterial communities found in the urogenital tract in males.

References

  1. 1.

    Power, M. L., Quaglieri, C. & Schulkin, J. Reproductive microbiomes. Reprod. Sci. 24, 1482–1492 (2017).

    PubMed  Google Scholar 

  2. 2.

    Sender, R., Fuchs, S. & Milo, R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164, 337–340 (2016).

    CAS  Google Scholar 

  3. 3.

    Sender, R., Fuchs, S. & Milo, R. Revised estimates for the number of human and bacteria cells in the body. PLOS Biol. 14, e1002533 (2016).

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Grice, E. A. & Segre, J. A. The human microbiome: our second genome. Annu. Rev. Genomics Hum. Genet. 13, 151–170 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Wang, B., Yao, M., Lv, L., Ling, Z. & Li, L. The human microbiota in health and disease. Engineering 3, 71–82 (2017).

    Google Scholar 

  6. 6.

    Kroon, S. J., Ravel, J. & Huston, W. M. Cervicovaginal microbiota, women’s health, and reproductive outcomes. Fertil. Steril. 110, 327–336 (2018).

    PubMed  Google Scholar 

  7. 7.

    Benner, M., Ferwerda, G., Joosten, I. & van der Molen, R. G. How uterine microbiota might be responsible for a receptive, fertile endometrium. Hum. Reprod. Update 24, 393–415 (2018).

    CAS  PubMed  Google Scholar 

  8. 8.

    Baker, J. M., Chase, D. M. & Herbst-Kralovetz, M. M. Uterine microbiota: residents, tourists, or invaders? Front. Immunol. 9, 208 (2018).

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Altmäe, S. Commentary: uterine microbiota: residents, tourists, or invaders? Front. Immunol. 9, 1874 (2018).

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Franasiak, J. M. & Scott, R. T. Endometrial microbiome. Curr. Opin. Obstet. Gynecol. 29, 146–152 (2017).

    PubMed  Google Scholar 

  11. 11.

    Moreno, I. & Franasiak, J. M. Endometrial microbiota-new player in town. Fertil. Steril. 108, 32–39 (2017).

    PubMed  Google Scholar 

  12. 12.

    Moreno, I. et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am. J. Obstet. Gynecol. 215, 684–703 (2016).

    PubMed  Google Scholar 

  13. 13.

    Altmäe, S. Uterine microbiota: a role beyond infection. EMJ Reprod. Heal. 6, 70–75 (2018).

    Google Scholar 

  14. 14.

    Franasiak, J. M. & Scott, R. T. Reproductive tract microbiome in assisted reproductive technologies. Fertil. Steril. 104, 1364–1371 (2015).

    PubMed  Google Scholar 

  15. 15.

    Nguyen, P. V., Kafka, J. K., Ferreira, V. H., Roth, K. & Kaushic, C. Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection. Cell. Mol. Immunol. 11, 410–427 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Weng, S. L. et al. Bacterial communities in semen from men of infertile couples: metagenomic sequencing reveals relationships of seminal microbiota to semen quality. PLOS ONE 9, e110152 (2014).

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Chen, H., Luo, T., Chen, T. & Wang, G. Seminal bacterial composition in patients with obstructive and non‑obstructive azoospermia. Exp. Ther. Med. 15, 2884–2890 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Monteiro, C. et al. Characterization of microbiota in male infertility cases uncovers differences in seminal hyperviscosity and oligoasthenoteratozoospermia possibly correlated with increased prevalence of infectious bacteria. Am. J. Reprod. Immunol. 79, e12838 (2018).

    PubMed  Google Scholar 

  19. 19.

    Mändar, R. et al. Seminal microbiome in men with and without prostatitis. Int. J. Urol. 24, 1–6 (2017).

    Google Scholar 

  20. 20.

    Koedooder, R. et al. Identification and evaluation of the microbiome in the female and male reproductive tract. Hum. Reprod. Update 25, 298–325 (2019).

    PubMed  Google Scholar 

  21. 21.

    Liu, C. M. et al. The semen microbiome and its relationship with local immunology and viral load in HIV infection. PLOS Pathog. 10, e1004262 (2014).

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Hou, D. et al. Microbiota of the seminal fluid from healthy and infertile men. Fertil. Steril. 100, 1261–1269.e3 (2013).

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Baud, D. et al. Sperm microbiota and its impact on semen parameters. Front. Microbiol. 10, 234 (2019).

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Mändar, R. et al. Complementary seminovaginal microbiome in couples. Res. Microbiol. 166, 440–447 (2015).

    PubMed  Google Scholar 

  25. 25.

    Mändar, R., Türk, S., Korrovits, P., Ausmees, K. & Punab, M. Impact of sexual debut on culturable human seminal microbiota. Andrology 6, 510–512 (2018).

    PubMed  Google Scholar 

  26. 26.

    Reece, A. S. Dying for love: perimenopausal degeneration of vaginal microbiome drives the chronic inflammation-malignant transformation of benign prostatic hyperplasia to prostatic adenocarcinoma. Med. Hypotheses 101, 44–47 (2017).

    PubMed  Google Scholar 

  27. 27.

    Kjaergaard, N. et al. Pyospermia and preterm, prelabor, rupture of membranes. Acta Obstet. Gynecol. Scand. 76, 528–531 (1997).

    CAS  PubMed  Google Scholar 

  28. 28.

    Wittemer, C. et al. [Abnormal bacterial colonisation of the vagina and implantation during assisted reproduction]. Gynecol. Obstet. Fertil. 32, 135–139 (2004).

    CAS  PubMed  Google Scholar 

  29. 29.

    Kenny, L. C. & Kell, D. B. Immunological tolerance, pregnancy, and preeclampsia: the roles of semen microbes and the father. Front. Med. 4, 239 (2018).

    Google Scholar 

  30. 30.

    Sisti, G., Kanninen, T. T. & Witkin, S. S. Maternal immunity and pregnancy outcome: focus on preconception and autophagy. Genes Immun. 17, 1–7 (2016).

    CAS  PubMed  Google Scholar 

  31. 31.

    Rando, O. J. & Simmons, R. A. I’m eating for two: parental dietary effects on offspring metabolism. Cell 161, 93–105 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Ricci, S. et al. Impact of asymptomatic genital tract infections on in vitro fertilization (IVF) outcome. PLOS ONE 13, e0207684 (2018).

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Damke, E., Kurscheidt, F. A., Irie, M. M. T., Gimenes, F. & Consolaro, M. E. L. Male partners of infertile couples with seminal positivity for markers of bacterial vaginosis have impaired fertility. Am. J. Mens Health 12, 2104–2115 (2018).

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    La Vignera, S., Vicari, E., Condorelli, R. A., D’Agata, R. & Calogero, A. E. Male accessory gland infection and sperm parameters (review). Int. J. Androl. 34, e330–e347 (2011).

    PubMed  Google Scholar 

  35. 35.

    Merino, G. et al. Bacterial infection and semen characteristics in infertile men. Arch. Androl. 35, 43–47 (1995).

    CAS  PubMed  Google Scholar 

  36. 36.

    Lacroix, J.-M., Jarvi, K., Batra, S. D., Heritz, D. M. & Mittelmana, M. PCR-based technique for the detection of bacteria in semen and urine. J. Microbiol. Methods 26, 61–71 (1996).

    CAS  Google Scholar 

  37. 37.

    Elsner, P. & Hartmann, A. A. Gardnerella vaginalis in the male upper genital tract: a possible source of reinfection of the female partner. Sex. Transm. Dis. 14, 122–123 (1987).

    CAS  PubMed  Google Scholar 

  38. 38.

    Ferlin, A. OR15-5: Effects of low sperm count go beyond fertility. Presented at The Endocrine Society Annual Meeting (2018).

  39. 39.

    Hanson, B. M., Eisenberg, M. L. & Hotaling, J. M. Male infertility: a biomarker of individual and familial cancer risk. Fertil. Steril. 109, 6–19 (2018).

    CAS  PubMed  Google Scholar 

  40. 40.

    Ferlin, A. et al. Sperm count and hypogonadism as markers of general male health. Eur. Urol. Focus https://doi.org/10.1016/j.euf.2019.08.001 (2019).

  41. 41.

    Javurek, A. B. et al. Discovery of a novel seminal fluid microbiome and influence of estrogen receptor alpha genetic status. Sci. Rep. 6, 1–14 (2016).

    Google Scholar 

  42. 42.

    Hanson, H. A. et al. Risk of childhood mortality in family members of men with poor semen quality. Hum. Reprod. 32, 239–247 (2016).

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    Sermondade, N. et al. BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum. Reprod. Update 19, 221–231 (2013).

    CAS  PubMed  Google Scholar 

  44. 44.

    Bieniek, J. M. et al. Influence of increasing body mass index on semen and reproductive hormonal parameters in a multi-institutional cohort of subfertile men. Fertil. Steril. 106, 1070–1075 (2016).

    CAS  PubMed  Google Scholar 

  45. 45.

    Hart, R. J. et al. Features of the metabolic syndrome in late adolescence are associated with impaired testicular function at 20 years of age. Hum. Reprod. 34, 389–402 (2019).

    CAS  PubMed  Google Scholar 

  46. 46.

    Younes, J. A. et al. Women and their microbes: the unexpected friendship. Trends Microbiol. 26, 16–32 (2018).

    CAS  PubMed  Google Scholar 

  47. 47.

    Valles-Colomer, M. et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat. Microbiol. 4, 623–632 (2019).

    CAS  PubMed  Google Scholar 

  48. 48.

    Cryan, J. F. & Dinan, T. G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 13, 701–712 (2012).

    CAS  PubMed  Google Scholar 

  49. 49.

    Mohajeri, M. H., La Fata, G., Steinert, R. E. & Weber, P. Relationship between the gut microbiome and brain function. Nutr. Rev. 76, 481–496 (2018).

    PubMed  Google Scholar 

  50. 50.

    Winter, G., Hart, R. A., Charlesworth, R. P. G. & Sharpley, C. F. Gut microbiome and depression: what we know and what we need to know. Rev. Neurosci. 29, 629–643 (2018).

    PubMed  Google Scholar 

  51. 51.

    Smith, L. K. & Wissel, E. F. Microbes and the mind: how bacteria shape affect, neurological processes, cognition, social relationships, development, and pathology. Perspect. Psychol. Sci. 14, 397–418 (2019).

    PubMed  Google Scholar 

  52. 52.

    Takagi, T. et al. Differences in gut microbiota associated with age, sex, and stool consistency in healthy Japanese subjects. J. Gastroenterol. 54, 53–63 (2018).

    PubMed  Google Scholar 

  53. 53.

    Hopkins, M. J., Sharp, R. & Macfarlane, G. T. Age and disease related changes in intestinal bacterial populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles. Gut 48, 198–205 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    He, Y. et al. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat. Med. 24, 1532–1535 (2018).

    CAS  PubMed  Google Scholar 

  55. 55.

    Deschasaux, M. et al. Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography. Nat. Med. 24, 1526–1531 (2018).

    CAS  PubMed  Google Scholar 

  56. 56.

    Goodrich, J. K. et al. Human genetics shape the gut microbiome. Cell 159, 789–799 (2014).

    CAS  PubMed Central  Google Scholar 

  57. 57.

    Dominianni, C. et al. Sex, body mass index, and dietary fiber intake influence the human gut microbiome. PLOS ONE 10, e0124599 (2015).

    PubMed  PubMed Central  Google Scholar 

  58. 58.

    Postler, T. S. & Ghosh, S. Understanding the holobiont: how microbial metabolites affect human health and shape the immune system. Cell Metab. 26, 110–130 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Goodrich, J. K. et al. Conducting a microbiome study. Cell 158, 250–262 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Suez, J. & Elinav, E. The path towards microbiome-based metabolite treatment. Nat. Microbiol. 2, 17075 (2017).

    CAS  PubMed  Google Scholar 

  61. 61.

    Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 1079–1094 (2015).

    CAS  PubMed  Google Scholar 

  62. 62.

    Lynch, S. V. & Pedersen, O. The human intestinal microbiome in health and disease. N. Engl. J. Med. 375, 2369–2379 (2016).

    CAS  Google Scholar 

  63. 63.

    Price, L. B. et al. The effects of circumcision on the penis microbiome. PLOS ONE 5, e8422 (2010).

    PubMed  PubMed Central  Google Scholar 

  64. 64.

    Vodstrcil, L. A. et al. The influence of sexual activity on the vaginal microbiota and Gardnerella vaginalis clade diversity in young women. PLOS ONE 12, e0171856 (2017).

    PubMed  PubMed Central  Google Scholar 

  65. 65.

    Javurek, A. B. et al. Consumption of a high-fat diet alters the seminal fluid and gut microbiomes in male mice. Reprod. Fertil. Dev. 29, 1602–1612 (2017).

    CAS  PubMed  Google Scholar 

  66. 66.

    Costea, P. I. et al. Towards standards for human fecal sample processing in metagenomic studies. Nat. Biotechnol. 35, 1069–1076 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Santiago, A. et al. Processing faecal samples: a step forward for standards in microbial community analysis. BMC Microbiol. 14, 112 (2014).

    PubMed  PubMed Central  Google Scholar 

  68. 68.

    O’Donnell, M. M. et al. Preparation of a standardised faecal slurry for ex-vivo microbiota studies which reduces inter-individual donor bias. J. Microbiol. Methods 129, 109–116 (2016).

    PubMed  Google Scholar 

  69. 69.

    Karstens, L. et al. Community profiling of the urinary microbiota: considerations for low-biomass samples. Nat. Rev. Urol. 15, 735–749 (2018).

    PubMed  PubMed Central  Google Scholar 

  70. 70.

    Castillo, J., Jodar, M. & Oliva, R. The contribution of human sperm proteins to the development and epigenome of the preimplantation embryo. Hum. Reprod. Update 24, 535–555 (2018).

    CAS  Google Scholar 

  71. 71.

    Ronquist, G. K. et al. Prostasomal DNA characterization and transfer into human sperm. Mol. Reprod. Dev. 78, 467–476 (2011).

    CAS  PubMed  Google Scholar 

  72. 72.

    Aalberts, M., Stout, T. A. E. & Stoorvogel, W. Prostasomes: extracellular vesicles from the prostate. Reproduction 147, R1–R14 (2014).

    CAS  PubMed  Google Scholar 

  73. 73.

    Drabovich, A. P., Saraon, P., Jarvi, K. & Diamandis, E. P. Seminal plasma as a diagnostic fluid for male reproductive system disorders. Nat. Rev. Urol. 11, 278–288 (2014).

    CAS  PubMed  Google Scholar 

  74. 74.

    Vojtech, L. et al. Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nucleic Acids Res. 42, 7290–7304 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Chiasserini, D. et al. Identification and partial characterization of two populations of prostasomes by a combination of dynamic light scattering and proteomic analysis. J. Membr. Biol. 248, 991–1004 (2015).

    CAS  Google Scholar 

  76. 76.

    Jodar, M., Sendler, E. & Krawetz, S. A. The protein and transcript profiles of human semen. Cell Tissue Res. 363, 85–96 (2016).

    CAS  Google Scholar 

  77. 77.

    Mändar, R. Microbiota of male genital tract: impact on the health of man and his partner. Pharmacol. Res. 69, 32–41 (2013).

    PubMed  Google Scholar 

  78. 78.

    Kiessling, A. A., Desmarais, B. M., Yin, H.-Z. Z., Loverde, J. & Eyre, R. C. Detection and identification of bacterial DNA in semen. Fertil. Steril. 90, 1744–1756 (2008).

    CAS  PubMed  Google Scholar 

  79. 79.

    Jarvi, K. et al. Polymerase chain reaction-based detection of bacteria in semen. Fertil. Steril. 66, 463–467 (1996).

    CAS  PubMed  Google Scholar 

  80. 80.

    Kermes, K., Punab, M., Lõivukene, K. & Mändar, R. Anaerobic seminal fluid micro-flora in chronic prostatitis/chronic pelvic pain syndrome patients. Anaerobe 9, 117–123 (2003).

    PubMed  Google Scholar 

  81. 81.

    Cavarretta, I. et al. The microbiome of the prostate tumor microenvironment. Eur. Urol. 72, 625–631 (2017).

    CAS  PubMed  Google Scholar 

  82. 82.

    Alfano, M. et al. Testicular microbiome in azoospermic men-first evidence of the impact of an altered microenvironment. Hum. Reprod. 33, 1212–1217 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83.

    Jeon, S. J. et al. Blood as a route of transmission of uterine pathogens from the gut to the uterus in cows. Microbiome 5, 109 (2017).

    PubMed Central  Google Scholar 

  84. 84.

    Levy, M., Kolodziejczyk, A. A., Thaiss, C. A. & Elinav, E. Dysbiosis and the immune system. Nat. Rev. Immunol. 17, 219–232 (2017).

    CAS  PubMed  Google Scholar 

  85. 85.

    Luca, F., Kupfer, S. S., Knights, D., Khoruts, A. & Blekhman, R. Functional genomics of host-microbiome interactions in humans. Trends Genet. 34, 30–40 (2018).

    CAS  PubMed  Google Scholar 

  86. 86.

    Opazo, M. C. et al. Intestinal microbiota influences non-intestinal related autoimmune diseases. Front. Microbiol. 9, 1–20 (2018).

    Google Scholar 

  87. 87.

    Nishimura, M. & Naito, S. Tissue-specific mRNA expression profiles of human toll-like receptors and related genes. Biol. Pharm. Bull. 28, 886–892 (2005).

    CAS  PubMed  Google Scholar 

  88. 88.

    Pudney, J. & Anderson, D. J. Expression of toll-like receptors in genital tract tissues from normal and HIV-infected men. Am. J. Reprod. Immunol. 65, 28–43 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Girling, J. E. & Hedger, M. P. Toll-like receptors in the gonads and reproductive tract: emerging roles in reproductive physiology and pathology. Immunol. Cell Biol. 85, 481–489 (2007).

    CAS  PubMed  Google Scholar 

  90. 90.

    Wira, C. R., Grant-Tschudy, K. S. & Crane-Godreau, M. A. Epithelial cells in the female reproductive tract: a central role as sentinels of immune protection. Am. J. Reprod. Immunol. 53, 65–76 (2005).

    CAS  PubMed  Google Scholar 

  91. 91.

    Round, J. L. et al. The toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 332, 974–977 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Petnicki-Ocwieja, T. et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc. Natl. Acad. Sci. USA 106, 15813–15818 (2009).

    CAS  PubMed  Google Scholar 

  93. 93.

    Türk, S., Mazzoli, S., Stšepetova, J., Kuznetsova, J. & Mändar, R. Coryneform bacteria in human semen: inter-assay variability in species composition detection and biofilm production ability. Microb. Ecol. Health Dis. 25, 1–6 (2014).

    Google Scholar 

  94. 94.

    Magri, V. et al. Multidisciplinary approach to prostatitis. Arch. Ital. Urol. Androl. 90, 227–248 (2019).

    PubMed  Google Scholar 

  95. 95.

    Cai, T. et al. Prostate calcifications: a case series supporting the microbial biofilm theory. Investig. Clin. Urol. 59, 187–193 (2018).

    PubMed  PubMed Central  Google Scholar 

  96. 96.

    Bartoletti, R. et al. The impact of biofilm-producing bacteria on chronic bacterial prostatitis treatment: results from a longitudinal cohort study. World J. Urol. 32, 737–742 (2014).

    CAS  Google Scholar 

  97. 97.

    D’Amore, R. et al. A comprehensive benchmarking study of protocols and sequencing platforms for 16S rRNA community profiling. BMC Genomics 17, 55 (2016).

    PubMed  PubMed Central  Google Scholar 

  98. 98.

    Glassing, A., Dowd, S. E., Galandiuk, S., Davis, B. & Chiodini, R. J. Inherent bacterial DNA contamination of extraction and sequencing reagents may affect interpretation of microbiota in low bacterial biomass samples. Gut Pathog. 8, 24 (2016).

    PubMed  PubMed Central  Google Scholar 

  99. 99.

    de Goffau, M. C. et al. Human placenta has no microbiome but can contain potential pathogens. Nature 572, 329–334 (2019).

    PubMed  Google Scholar 

  100. 100.

    Eisenhofer, R. et al. Contamination in low microbial biomass microbiome studies: issues and recommendations. Trends Microbiol. 27, 105–117 (2019).

    CAS  Google Scholar 

  101. 101.

    Salter, S. J. et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol. 12, 87 (2014).

    PubMed  PubMed Central  Google Scholar 

  102. 102.

    Hallmaier-Wacker, L. K., Lueert, S., Roos, C. & Knauf, S. The impact of storage buffer, DNA extraction method, and polymerase on microbial analysis. Sci. Rep. 8, 6292 (2018).

    PubMed  PubMed Central  Google Scholar 

  103. 103.

    Chen, Z. et al. Impact of preservation method and 16S rRNA hypervariable region on gut microbiota profiling. mSystems 4, e00271–18 (2019).

    PubMed  PubMed Central  Google Scholar 

  104. 104.

    Lim, M. Y., Song, E.-J., Kim, S. H., Lee, J. & Nam, Y.-D. Comparison of DNA extraction methods for human gut microbial community profiling. Syst. Appl. Microbiol. 41, 151–157 (2018).

    CAS  PubMed  Google Scholar 

  105. 105.

    Thomas, V., Clark, J. & Doré, J. Fecal microbiota analysis: an overview of sample collection methods and sequencing strategies. Future Microbiol. 10, 1485–1504 (2015).

    CAS  PubMed  Google Scholar 

  106. 106.

    Lambert, J. A. et al. Novel PCR-based methods enhance characterization of vaginal microbiota in a bacterial vaginosis patient before and after treatment. Appl. Environ. Microbiol. 79, 4181–4185 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Gohl, D. M. et al. Systematic improvement of amplicon marker gene methods for increased accuracy in microbiome studies. Nat. Biotechnol. 34, 942–949 (2016).

    CAS  PubMed  Google Scholar 

  108. 108.

    Wu, J.-Y. Y. et al. Effects of polymerase, template dilution and cycle number on PCR based 16 S rRNA diversity analysis using the deep sequencing method. BMC Microbiol. 10, 255 (2010).

    PubMed  PubMed Central  Google Scholar 

  109. 109.

    Clooney, A. G. et al. Comparing apples and oranges?: Next generation sequencing and its impact on microbiome analysis. PLOS ONE 11, e0148028 (2016).

    PubMed  PubMed Central  Google Scholar 

  110. 110.

    Multinu, F. et al. Systematic bias introduced by genomic dna template dilution in 16S rRNA gene-targeted microbiota profiling in human stool homogenates. mSphere 3, e00560–17 (2018).

    Google Scholar 

  111. 111.

    Aron-Wisnewsky, J. & Clément, K. The gut microbiome, diet, and links to cardiometabolic and chronic disorders. Nat. Rev. Nephrol. 12, 169–181 (2016).

    CAS  PubMed  Google Scholar 

  112. 112.

    Plummer, E., Twin, J., Bulach, D. M., Garland, S. M. & Tabrizi, S. N. A comparison of three bioinformatics pipelines for the analysis of preterm gut microbiota using 16S rRNA gene sequencing data. J. Proteom. Bioinform Cit. 8, 283–291 (2015).

    Google Scholar 

  113. 113.

    Callahan, B. J., McMurdie, P. J. & Holmes, S. P. Exact sequence variants should replace operational taxonomic units in marker-gene data analysis. ISME J. 11, 2639–2643 (2017).

    PubMed  PubMed Central  Google Scholar 

  114. 114.

    Ma, Z. & Li, L. Semen microbiome biogeography: an analysis based on a chinese population study. Front. Microbiol. 9, 3333 (2019).

    PubMed  PubMed Central  Google Scholar 

  115. 115.

    Rehewy, M. S., Hafez, E. S., Thomas, A. & Brown, W. J. Aerobic and anaerobic bacterial flora in semen from fertile and infertile groups of men. Arch. Androl. 2, 263–268 (1979).

    CAS  PubMed  Google Scholar 

  116. 116.

    Willén, M., Holst, E., Myhre, E. B. & Olsson, A. M. The bacterial flora of the genitourinary tract in healthy fertile men. Scand. J. Urol. Nephrol. 30, 387–393 (1996).

    PubMed  Google Scholar 

  117. 117.

    Ivanov, I. B., Kuzmin, M. D. & Gritsenko, V. A. Microflora of the seminal fluid of healthy men and men suffering from chronic prostatitis syndrome. Int. J. Androl. 32, 462–467 (2009).

    PubMed  Google Scholar 

  118. 118.

    Punab, M., Lõivukene, K., Kermes, K. & Mändar, R. The limit of leucocytospermia from the microbiological viewpoint. Andrologia 35, 271–278 (2003).

    PubMed  Google Scholar 

  119. 119.

    Korrovits, P., Punab, M., Türk, S. & Mändar, R. Seminal microflora in asymptomatic inflammatory (NIH IV category) prostatitis. Eur. Urol. 50, 1338–1344; discussion 1344–1346 (2006).

    PubMed  Google Scholar 

  120. 120.

    Türk, S., Korrovits, P., Punab, M. & Mändar, R. Coryneform bacteria in semen of chronic prostatitis patients. Int. J. Androl. 30, 123–128 (2007).

    PubMed  Google Scholar 

  121. 121.

    Petrova, M. I., Lievens, E., Malik, S., Imholz, N. & Lebeer, S. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front. Physiol. 6, 81 (2015).

    PubMed  PubMed Central  Google Scholar 

  122. 122.

    Nelson, D. E. et al. Characteristic male urine microbiomes associate with asymptomatic sexually transmitted infection. PLOS ONE 5, e14116 (2010).

    PubMed  PubMed Central  Google Scholar 

  123. 123.

    World Health Organization. Laboratory Manual for the Examination and Processing of Human Semen 5th edn (Geneva, Switzerland, 2011).

  124. 124.

    Barbonetti, A. et al. Effect of vaginal probiotic lactobacilli on in vitro-induced sperm lipid peroxidation and its impact on sperm motility and viability. Fertil. Steril. 95, 2485–2488 (2011).

    CAS  PubMed  Google Scholar 

  125. 125.

    Agarwal, A., Mulgund, A., Hamada, A. & Chyatte, M. R. A unique view on male infertility around the globe. Reprod. Biol. Endocrinol. 13, 37 (2015).

    PubMed  PubMed Central  Google Scholar 

  126. 126.

    Jungwirth, A. et al. European Association of Urology guidelines on male infertility: the 2012 update. Eur. Urol. 62, 324–332 (2012).

    PubMed  Google Scholar 

  127. 127.

    Winters, B. R. & Walsh, T. J. The epidemiology of male infertility. Urol. Clin. North Am. 41, 195–204 (2014).

    PubMed  Google Scholar 

  128. 128.

    Calogero, A. E., Duca, Y., Condorelli, R. A. & La Vignera, S. Male accessory gland inflammation, infertility, and sexual dysfunctions: a practical approach to diagnosis and therapy. Andrology 5, 1064–1072 (2017).

    CAS  PubMed  Google Scholar 

  129. 129.

    Du Plessis, S. S., Gokul, S. & Agarwal, A. Semen hyperviscosity: causes, consequences, and cures. Front. Biosci. (Elite Ed). 5, 224–231 (2013).

    PubMed  Google Scholar 

  130. 130.

    Punab, M., Kullisaar, T. & Mändar, R. Male infertility workup needs additional testing of expressed prostatic secretion and/or post-massage urine. PLOS ONE 8, e82776 (2013).

    PubMed  PubMed Central  Google Scholar 

  131. 131.

    Condorelli, R. A., Russo, G. I., Calogero, A. E., Morgia, G. & La Vignera, S. Chronic prostatitis and its detrimental impact on sperm parameters: a systematic review and meta-analysis. J. Endocrinol. Invest. 40, 1209–1218 (2017).

    CAS  PubMed  Google Scholar 

  132. 132.

    Mogra, N., Dhruva, A. & Kothari, L. K. Non-specific seminal tract infection and male infertility: a bacteriological study. J. Postgrad. Med. 27, 99–104 (1981).

    CAS  PubMed  Google Scholar 

  133. 133.

    Mashaly, M., Masallat, D. T., Elkholy, A. A., Abdel-Hamid, I. A. & Mostafa, T. Seminal Corynebacterium strains in infertile men with and without leucocytospermia. Andrologia 48, 355–359 (2016).

    CAS  PubMed  Google Scholar 

  134. 134.

    Esfandiari, N., Saleh, R. A., Abdoos, M., Rouzrokh, A. & Nazemian, Z. Positive bacterial culture of semen from infertile men with asymptomatic leukocytospermia. Int. J. Fertil. Womens. Med. 47, 265–270 (2002).

    PubMed  Google Scholar 

  135. 135.

    De Francesco, M. A., Negrini, R., Ravizzola, G., Galli, P. & Manca, N. Bacterial species present in the lower male genital tract: a five-year retrospective study. Eur. J. Contracept. Reprod. Health Care 16, 47–53 (2011).

    PubMed  Google Scholar 

  136. 136.

    Domes, T. et al. The incidence and effect of bacteriospermia and elevated seminal leukocytes on semen parameters. Fertil. Steril. 97, 1050–1055 (2012).

    PubMed  Google Scholar 

  137. 137.

    Filipiak, E. et al. Presence of aerobic micro-organisms and their influence on basic semen parameters in infertile men. Andrologia 47, 826–831 (2015).

    CAS  PubMed  Google Scholar 

  138. 138.

    Palini, S. et al. A new micro swim-up procedure for sperm preparation in ICSI treatments: preliminary microbiological testing. JBRA Assist. Reprod. 20, 94–98 (2016).

    PubMed  PubMed Central  Google Scholar 

  139. 139.

    Cumming, J. A., Dawes, J. & Hargreave, T. B. Granulocyte elastase levels do not correlate with anaerobic and aerobic bacterial growth in seminal plasma from infertile men. Int. J. Androl. 13, 273–277 (1990).

    CAS  PubMed  Google Scholar 

  140. 140.

    Gregoriou, O. et al. Culture of seminal fluid in infertile men and relationship to semen evaluation. Int. J. Gynaecol. Obstet. 28, 149–153 (1989).

    CAS  PubMed  Google Scholar 

  141. 141.

    Colpi, G. M., Zanollo, A., Roveda, M. L., Tommasini-Degna, A. & Beretta, G. Anaerobic and aerobic bacteria in secretions of prostate and seminal vesicles of infertile men. Arch. Androl. 9, 175–181 (1982).

    CAS  PubMed  Google Scholar 

  142. 142.

    Balmelli, T. et al. Bacteroides ureolyticus in men consulting for infertility. Andrologia 26, 35–38 (1994).

    CAS  PubMed  Google Scholar 

  143. 143.

    Virecoulon, F. et al. Bacterial flora of the low male genital tract in patients consulting for infertility. Andrologia 37, 160–165 (2005).

    CAS  PubMed  Google Scholar 

  144. 144.

    Edström, A. M. L. et al. The major bactericidal activity of human seminal plasma is zinc-dependent and derived from fragmentation of the semenogelins. J. Immunol. 181, 3413–3421 (2008).

    PubMed  PubMed Central  Google Scholar 

  145. 145.

    Flint, M., du Plessis, S. S. & Menkveld, R. Revisiting the assessment of semen viscosity and its relationship to leucocytospermia. Andrologia 46, 837–841 (2014).

    CAS  PubMed  Google Scholar 

  146. 146.

    Gimenes, F. et al. Male infertility: a public health issue caused by sexually transmitted pathogens. Nat. Rev. Urol. 11, 672–687 (2014).

    PubMed  Google Scholar 

  147. 147.

    Combaz-Söhnchen, N. & Kuhn, A. A systematic review of mycoplasma and ureaplasma in urogynaecology. Geburtshilfe Frauenheilkd. 77, 1299–1303 (2017).

    PubMed  PubMed Central  Google Scholar 

  148. 148.

    Boeri, L. et al. High-risk human papillomavirus in semen is associated with poor sperm progressive motility and a high sperm DNA fragmentation index in infertile men. Hum. Reprod. 34, 209–217 (2019).

    PubMed  Google Scholar 

  149. 149.

    Yow, M. A. et al. Characterisation of microbial communities within aggressive prostate cancer tissues. Infect. Agent. Cancer 12, 4 (2017).

    PubMed  PubMed Central  Google Scholar 

  150. 150.

    Brede, C. M. & Shoskes, D. A. The etiology and management of acute prostatitis. Nat. Rev. Urol. 8, 207–212 (2011).

    CAS  Google Scholar 

  151. 151.

    Nickel, J. The prostatitis manual (Bladon Medical Publishing, 2002).

  152. 152.

    Domingue, G. J. & Hellstrom, W. J. Prostatitis. Clin. Microbiol. Rev. 11, 604–613 (1998).

    PubMed  PubMed Central  Google Scholar 

  153. 153.

    Vicari, L. O. et al. Effect of levofloxacin treatment on semen hyperviscosity in chronic bacterial prostatitis patients. Andrologia 48, 380–388 (2016).

    CAS  Google Scholar 

  154. 154.

    Heras-Cañas, V. et al. [Chronic bacterial prostatitis. Clinical and microbiological study of 332 cases]. Med. Clin. 147, 144–147 (2016).

    Google Scholar 

  155. 155.

    Iovene, M. R. et al. Enrichment of semen culture in the diagnosis of bacterial prostatitis. J. Microbiol. Methods 154, 124–126 (2018).

    CAS  PubMed  Google Scholar 

  156. 156.

    Mobley, D. F. Semen cultures in the diagnosis of bacterial prostatitis. J. Urol. 114, 83–85 (1975).

    CAS  PubMed  Google Scholar 

  157. 157.

    Eijsten, A., Hauri, D. & Knönagel, H. [Bacteriology of the ejaculate — a useful study?]. Urologe. A 27, 340–342 (1988).

    CAS  PubMed  Google Scholar 

  158. 158.

    Weidner, W., Jantos, C., Schiefer, H. G., Haidl, G. & Friedrich, H. J. Semen parameters in men with and without proven chronic prostatitis. Arch. Androl. 26, 173–183 (1991).

    CAS  PubMed  Google Scholar 

  159. 159.

    Magri, V. et al. Microscopic and microbiological findings for evaluation of chronic prostatitis. Arch. Ital. di Urol. Androl. 77, 135–138 (2005).

    Google Scholar 

  160. 160.

    Rizzo, M., Marchetti, F., Travaglini, F., Trinchieri, A. & Nickel, J. C. Clinical characterization of the prostatitis patient in Italy: a prospective urology outpatient study. World J. Urol. 23, 61–66 (2005).

    PubMed  Google Scholar 

  161. 161.

    Budía, A. et al. Value of semen culture in the diagnosis of chronic bacterial prostatitis: a simplified method. Scand. J. Urol. Nephrol. 40, 326–331 (2006).

    PubMed  Google Scholar 

  162. 162.

    Zegarra Montes, L. Z. M. R., Sanchez Mejia, A. A., Loza Munarriz, C. A. & Gutierrez, E. C. Semen and urine culture in the diagnosis of chronic bacterial prostatitis. Int. Braz. J. Urol. 34, 30–37; discussion 38–40 (2008).

    PubMed  Google Scholar 

  163. 163.

    Magri, V. et al. Semen analysis in chronic bacterial prostatitis: diagnostic and therapeutic implications. Asian J. Androl. 11, 461–477 (2009).

    PubMed  PubMed Central  Google Scholar 

  164. 164.

    Nickel, J. C. et al. Search for microorganisms in men with urologic chronic pelvic pain syndrome: a culture-independent analysis in the mapp research network. J. Urol. 194, 127–135 (2015).

    PubMed  PubMed Central  Google Scholar 

  165. 165.

    Hou, D.-S. et al. Characterisation of the bacterial community in expressed prostatic secretions from patients with chronic prostatitis/chronic pelvic pain syndrome and infertile men: a preliminary investigation. Asian J. Androl. 14, 566–573 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. 166.

    Mårdh, P. A. & Colleen, S. Search for uro-genital tract infections in patients with symptoms of prostatitis. Studies on aerobic and strictly anaerobic bacteria, mycoplasmas, fungi, trichomonads and viruses. Scand. J. Urol. Nephrol. 9, 8–16 (1975).

    PubMed  Google Scholar 

  167. 167.

    Schaeffer, A. J. et al. Leukocyte and bacterial counts do not correlate with severity of symptoms in men with chronic prostatitis: the National Institutes of Health Chronic Prostatitis Cohort Study. J. Urol. 168, 1048–1053 (2002).

    Google Scholar 

  168. 168.

    Nickel, J. C. et al. Leukocytes and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome compared to asymptomatic controls. J. Urol. 170, 818–822 (2003).

    Google Scholar 

  169. 169.

    Liu, L., Yang, J. & Lu, F. Urethral dysbacteriosis as an underlying, primary cause of chronic prostatitis: potential implications for probiotic therapy. Med. Hypotheses 73, 741–743 (2009).

    PubMed  Google Scholar 

  170. 170.

    Siqueira, J. F. & Rôças, I. N. Microbiology and treatment of acute apical abscesses. Clin. Microbiol. Rev. 26, 255–273 (2013).

    CAS  PubMed Central  Google Scholar 

  171. 171.

    Brook, I. Bacterial synergy in pelvic inflammatory disease. Arch. Gynecol. Obstet. 241, 133–143 (1987).

    CAS  Google Scholar 

  172. 172.

    Vicari, E., Calogero, A. E., Condorelli, R. A., Vicari, L. O. & La Vignera, S. Male accessory gland infection frequency in infertile patients with chronic microbial prostatitis and irritable bowel syndrome. Int. J. Androl. 35, 183–189 (2012).

    CAS  PubMed  Google Scholar 

  173. 173.

    Santoianni, J. E., De Paulis, A. N., Cardoso, E. M., Gonzalez, B. N. & Predari, S. C. Assessment in the diagnosis of male chronic genital tract infection. Medicina 60, 331–334 (2000).

    CAS  PubMed  Google Scholar 

  174. 174.

    Manzoor, M. A. P. & Rekha, P.-D. Prostate cancer: microbiome — the ‘unforeseen organ’. Nat. Rev. Urol. 14, 521–522 (2017).

    Google Scholar 

  175. 175.

    Sfanos, K. S., Yegnasubramanian, S., Nelson, W. G. & De Marzo, A. M. The inflammatory microenvironment and microbiome in prostate cancer development. Nat. Rev. Urol. 15, 11–24 (2018).

    PubMed  Google Scholar 

  176. 176.

    Porter, C. M., Shrestha, E., Peiffer, L. B. & Sfanos, K. S. The microbiome in prostate inflammation and prostate cancer. Prostate Cancer Prostatic Dis. 21, 345–354 (2018).

    CAS  PubMed  Google Scholar 

  177. 177.

    Amirian, E. et al. Potential role of gastrointestinal microbiota composition in prostate cancer risk. Infect. Agent. Cancer 8, 42 (2013).

    PubMed  PubMed Central  Google Scholar 

  178. 178.

    Golombos, D. M. et al. The role of gut microbiome in the pathogenesis of prostate cancer: a prospective, pilot study. Urology 111, 122–128 (2018).

    PubMed  Google Scholar 

  179. 179.

    Wolk, A. Diet, lifestyle and risk of prostate cancer. Acta Oncol. 44, 277–281 (2005).

    PubMed  Google Scholar 

  180. 180.

    Puhr, M. et al. Inflammation, microbiota, and prostate cancer. Eur. Urol. Focus. 2, 374–382 (2016).

    PubMed  Google Scholar 

  181. 181.

    Sheflin, A. M., Whitney, A. K. & Weir, T. L. Cancer-promoting effects of microbial dysbiosis. Curr. Oncol. Rep. 16, 406 (2014).

    PubMed  PubMed Central  Google Scholar 

  182. 182.

    Alfano, M. et al. The interplay of extracellular matrix and microbiome in urothelial bladder cancer. Nat. Rev. Urol. 13, 77–90 (2016).

    CAS  PubMed  Google Scholar 

  183. 183.

    Schwabe, R. F. & Jobin, C. The microbiome and cancer. Nat. Rev. Cancer 13, 800–812 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  184. 184.

    Cavalieri, E. et al. Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention. Biochim. Biophys. Acta Rev. Cancer 1766, 63–78 (2006).

    CAS  Google Scholar 

  185. 185.

    Feng, Y. et al. Metagenomic analysis reveals a rich bacterial content in high-risk prostate tumors from African men. Prostate 79, 1731–1738 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. 186.

    Xie, H. et al. [Detection of 16S ribosomal RNA gene of bacteria in prostate tissues of adults]. Zhonghua Yi Xue Za Zhi 86, 976–978 (2006).

    CAS  PubMed  Google Scholar 

  187. 187.

    Hochreiter, W. W., Duncan, J. L. & Schaeffer, A. J. Evaluation of the bacterial flora of the prostate using a 16S rRNA gene based polymerase chain reaction. J. Urol. 163, 127–130 (2000).

    CAS  PubMed  Google Scholar 

  188. 188.

    Krieger, J. N. & Riley, D. E. Prostatitis: what is the role of infection. Int. J. Antimicrob. Agents 19, 475–479 (2002).

    CAS  PubMed  Google Scholar 

  189. 189.

    Leskinen, M. J. et al. Negative bacterial polymerase chain reaction (PCR) findings in prostate tissue from patients with symptoms of chronic pelvic pain syndrome (CPPS) and localized prostate cancer. Prostate 55, 105–110 (2003).

    PubMed  Google Scholar 

  190. 190.

    Shrestha, E. et al. Profiling the urinary microbiome in men with positive versus negative biopsies for prostate cancer. J. Urol. 199, 161–171 (2018).

    PubMed  Google Scholar 

  191. 191.

    Lupo, F. & Ingersoll, M. A. Is bacterial prostatitis a urinary tract infection? Nat. Rev. Urol. 16, 203–204 (2019).

    PubMed  Google Scholar 

  192. 192.

    Kim, C. J. et al. Can probiotics reduce inflammation and enhance gut immune health in people living with HIV: study designs for the Probiotic Visbiome for Inflammation and Translocation (PROOV IT) pilot trials. HIV Clin. Trials 17, 147–157 (2016).

    CAS  PubMed  Google Scholar 

  193. 193.

    Hladik, F. & McElrath, M. J. Setting the stage: host invasion by HIV. Nat. Rev. Immunol. 8, 447–457 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  194. 194.

    Baeten, J. M. et al. Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Sci. Transl. Med. 3, 77ra29 (2011).

    PubMed  PubMed Central  Google Scholar 

  195. 195.

    Kalichman, S. C., Di Berto, G. & Eaton, L. Human immunodeficiency virus viral load in blood plasma and semen: review and implications of empirical findings. Sex. Transm. Dis. 35, 55–60 (2008).

    PubMed  Google Scholar 

  196. 196.

    Schwebke, J. R., Richey, C. M. & Weiss, H. L. Correlation of behaviors with microbiological changes in vaginal flora. J. Infect. Dis. 180, 1632–1636 (1999).

    CAS  PubMed  Google Scholar 

  197. 197.

    Vallor, A. C., Antonio, M. A., Hawes, S. E. & Hillier, S. L. Factors associated with acquisition of, or persistent colonization by, vaginal lactobacilli: role of hydrogen peroxide production. J. Infect. Dis. 184, 1431–1436 (2001).

    CAS  PubMed  Google Scholar 

  198. 198.

    Beigi, R. H., Wiesenfeld, H. C., Hillier, S. L., Straw, T. & Krohn, M. A. Factors associated with absence of H2O2-producing Lactobacillus among women with bacterial vaginosis. J. Infect. Dis. 191, 924–929 (2005).

    PubMed  Google Scholar 

  199. 199.

    Cherpes, T. L., Hillier, S. L., Meyn, L. A., Busch, J. L. & Krohn, M. A. A delicate balance: risk factors for acquisition of bacterial vaginosis include sexual activity, absence of hydrogen peroxide-producing lactobacilli, black race, and positive herpes simplex virus type 2 serology. Sex. Transm. Dis. 35, 78–83 (2008).

    PubMed  Google Scholar 

  200. 200.

    Brotman, R. M., Ravel, J., Cone, R. A. & Zenilman, J. M. Rapid fluctuation of the vaginal microbiota measured by gram stain analysis. Sex. Transm. Infect. 86, 297–302 (2010).

    PubMed  PubMed Central  Google Scholar 

  201. 201.

    Plummer, E. L. et al. Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: acceptability, tolerability and impact on the genital microbiota of couples — a pilot study. PLOS ONE 13, e0190199 (2018).

    PubMed  PubMed Central  Google Scholar 

  202. 202.

    Morison, L. et al. Bacterial vaginosis in relation to menstrual cycle, menstrual protection method, and sexual intercourse in rural Gambian women. Sex. Transm. Infect. 81, 242–247 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  203. 203.

    Hay, P. E., Ugwumadu, A. & Chowns, J. Sex, thrush and bacterial vaginosis. Int. J. STD AIDS 8, 603–608 (1997).

    CAS  PubMed  Google Scholar 

  204. 204.

    Verstraelen, H., Verhelst, R., Vaneechoutte, M. & Temmerman, M. The epidemiology of bacterial vaginosis in relation to sexual behaviour. BMC Infect. Dis. 10, 81 (2010).

    PubMed  PubMed Central  Google Scholar 

  205. 205.

    Tandogdu, Z. & Wagenlehner, F. M. E. Global epidemiology of urinary tract infections. Curr. Opin. Infect. Dis. 29, 73–79 (2016).

    PubMed  Google Scholar 

  206. 206.

    Lisboa, C. et al. Genital candidosis in heterosexual couples. J. Eur. Acad. Dermatology Venereol. 25, 145–151 (2011).

    CAS  Google Scholar 

  207. 207.

    Nelson, D. E. et al. Bacterial communities of the coronal sulcus and distal urethra of adolescent males. PLOS ONE 7, 1–9 (2012).

    Google Scholar 

  208. 208.

    Kelley, C. F. et al. The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention. Mucosal. Immunol. 10, 996–1007 (2017).

    CAS  PubMed  Google Scholar 

  209. 209.

    Armstrong, A. J. S. et al. An exploration of prevotella-rich microbiomes in HIV and men who have sex with men. Microbiome 6, 198 (2018).

    PubMed  PubMed Central  Google Scholar 

  210. 210.

    Noguera-Julian, M. et al. Gut microbiota linked to sexual preference and HIV infection. EBioMedicine 5, 135–146 (2016).

    PubMed  PubMed Central  Google Scholar 

  211. 211.

    Pan, W.-H. et al. Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development. Genome Med. 10, 27 (2018).

    PubMed  PubMed Central  Google Scholar 

  212. 212.

    Thion, M. S. et al. Microbiome influences prenatal and adult microglia in a sex-specific manner. Cell 172, 500–516.e16 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  213. 213.

    Lannon, S. M. R. et al. Parallel detection of lactobacillus and bacterial vaginosis-associated bacterial DNA in the chorioamnion and vagina of pregnant women at term. J. Matern. Fetal. Neonatal Med. 32, 2702–2710 (2019).

    PubMed  Google Scholar 

  214. 214.

    Watkins, A. J. & Sinclair, K. D. Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice. Am. J. Physiol. Circ. Physiol. 306, H1444–H1452 (2014).

    CAS  Google Scholar 

  215. 215.

    Carone, B. R. et al. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143, 1084–1096 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  216. 216.

    Dardmeh, F. et al. Lactobacillus rhamnosus PB01 (DSM 14870) supplementation affects markers of sperm kinematic parameters in a diet-induced obesity mice model. PLOS ONE 12, e0185964 (2017).

    PubMed  PubMed Central  Google Scholar 

  217. 217.

    Inatomi, T. & Otomaru, K. Effect of dietary probiotics on the semen traits and antioxidative activity of male broiler breeders. Sci. Rep. 8, 5874 (2018).

    PubMed  PubMed Central  Google Scholar 

  218. 218.

    Valcarce, D. G. et al. Probiotic administration improves sperm quality in asthenozoospermic human donors. Benef. Microbes 8, 193–206 (2017).

    CAS  PubMed  Google Scholar 

  219. 219.

    Maretti, C. & Cavallini, G. The association of a probiotic with a prebiotic (Flortec, Bracco) to improve the quality/quantity of spermatozoa in infertile patients with idiopathic oligoasthenoteratospermia: a pilot study. Andrology 5, 439–444 (2017).

    CAS  PubMed  Google Scholar 

  220. 220.

    Senok, A. C., Verstraelen, H., Temmerman, M. & Botta, G. A. Probiotics for the treatment of bacterial vaginosis. Cochrane Database Syst. Rev. 4, CD006289 (2009).

    Google Scholar 

  221. 221.

    Collins, S. L. et al. Promising prebiotic candidate established by evaluation of lactitol, lactulose, raffinose, and oligofructose for maintenance of a lactobacillus-dominated vaginal microbiota. Appl. Environ. Microbiol. 84, e02200–e02217 (2018).

    PubMed  PubMed Central  Google Scholar 

  222. 222.

    Khalesi, S. et al. A review of probiotic supplementation in healthy adults: helpful or hype? Eur. J. Clin. Nutr. 73, 24–37 (2018).

    PubMed  Google Scholar 

  223. 223.

    Wong, A. C. & Levy, M. New approaches to microbiome-based therapies. mSystems 4, e00122–19 (2019).

    PubMed  PubMed Central  Google Scholar 

  224. 224.

    Scarpellini, E. et al. The human gut microbiota and virome: potential therapeutic implications. Dig. Liver Dis. 47, 1007–1012 (2015).

    PubMed  Google Scholar 

  225. 225.

    Focà, A. et al. Gut inflammation and immunity: what is the role of the human gut virome? Mediators Inflamm. 2015, 326032 (2015).

    PubMed  PubMed Central  Google Scholar 

  226. 226.

    Lugli, G. A. et al. Prophages of the genus Bifidobacterium as modulating agents of the infant gut microbiota. Environ. Microbiol. 18, 2196–2213 (2016).

    PubMed  Google Scholar 

  227. 227.

    Miller-Ensminger, T. et al. Bacteriophages of the urinary microbiome. J. Bacteriol. 200, e00738–17 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  228. 228.

    Moustafa, A. et al. Microbial metagenome of urinary tract infection. Sci. Rep. 8, 4333 (2018).

    PubMed  PubMed Central  Google Scholar 

  229. 229.

    Ma, J. et al. Association between BMI and semen quality: an observational study of 3966 sperm donors. Hum. Reprod. 34, 155–162 (2019).

    PubMed  Google Scholar 

  230. 230.

    Zangara, M. T. & McDonald, C. How diet and the microbiome shape health or contribute to disease: a mini-review of current models and clinical studies. Exp. Biol. Med. 244, 484–493 (2019).

    CAS  Google Scholar 

Download references

Acknowledgements

S.A. is funded by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and the European Regional Development Fund (FEDER): grants RYC-2016-21199 and ENDORE SAF2017-87526; Programa Operativo FEDER Andalucía (B-CTS-500-UGR18) and by the University of Granada Plan Propio de Investigación 2016 —Excellence actions: Unit of Excellence on Exercise and Health (UCEES) — and Plan Propio de Investigación 2018 — Programa Contratos-Puente, and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades, European Regional Development Funds (ref. SOMM17/6107/UGR). R.M. is funded by the Estonian Research Council (grant No. IUT34-19), the Estonian Ministry of Education and Research (grant No. KOGU-HUMB) and Enterprise Estonia (grant No. EU48695).

Author information

Affiliations

Authors

Contributions

All the authors researched the data for the article, participated in the discussion of its content, wrote the article and critically reviewed the manuscript.

Corresponding author

Correspondence to Signe Altmäe.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

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

Glossary

Microbiota

A community of microorganisms present in a defined environment.

Next-generation sequencing

(NGS). Technique to detect microbial communities.

Tourists

Transient microbial population that is readily eliminated.

Invaders

Microorganisms that are present in particular diseased states, a transient population that contribute to disease.

Residents

‘Healthy’ bacterial residents that maintain homeostasis, a stable population.

Microbiome

The entire habitat that includes the microorganisms (bacteria, viruses, archaea, and lower and higher eukaryotes), their genomes and the surrounding environmental conditions, including the products of the microbiota and the host environment.

Seminal microbiome

The microbiome of the male ejaculate and reproductive tract.

Postbiotics

Metabolic by-products of live (probiotic) bacteria.

qPCR

Quantitative polymerase chain reaction (to detect specific microorganisms).

Decomplementary activity

Microbial inhibitor of complement.

Oestrobolome

The collection of microorganisms capable of metabolizing oestrogens.

Shannon Index

A measure of the richness and evenness in a given sample.

Methylome

Whole set of nucleic acid methylation modifications in genome.

Transcriptome

Whole set of messenger RNA molecules expressed from the genome.

Prebiotics

Compounds in food that induce growth or activity of beneficial microorganisms.

Probiotics

Live bacteria and yeasts promoted as having various health benefits.

Synbiotics

Food ingredients or dietary supplements combining probiotics and prebiotics in a form of synergism.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Altmäe, S., Franasiak, J.M. & Mändar, R. The seminal microbiome in health and disease. Nat Rev Urol 16, 703–721 (2019). https://doi.org/10.1038/s41585-019-0250-y

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing