A New Perspective on Infertility: Microbiota

Yıl 2024, , 299 - 305, 02.06.2024

Kübra Özyer , Sümeyye Kemaneci

https://doi.org/10.61399/ikcusbfd.1219405

Öz

A rapid decline in total fertility rate has been seen worldwide. Increasing infertility rates are among the causes of this condition, that is stated that 10-15% of couples are affected by infertility. While many factors such as genital infections, ovarian reserve deficiency, ovulation irregularity, obesity have been shown as the cause of infertility, microbiota has been included among these factors with a new perspective in recent years. Gut microbiota has the ability to regulate sex hormones and metabolites, which is essential for reproductive status and optimal levels. Dysbiosis of the intestinal microbiota can lead to the deterioration of the metabolism of sex hormones, especially estrogen, and may lead to various reproductive health problems including endometriosis, polycystic ovary syndrome, endometrial hyperplasia. While the female and male genital organs contain various microorganisms, Lactobacillus is the dominant flora, and this dominance is associated with reproductive system health, fertility, and healthy pregnancy. Although it is stated that various microorganisms in the male urogenital system are associated with semen quality, it is stated that dysbiosis of the male urogenital microbiota causes infections, a decrease in sperm quality, and various reproductive disorders. Negative changes in the microbiota are associated with abortion, still/preterm birth, recurrent implantation failure, preeclampsia, gestational diabetes and many other adverse pregnancy outcomes during pregnancy. The purpose of this review is to investigate the relationship between human intestinal and urogenital microbiota and fertility.

Anahtar Kelimeler

Gut microbiota, fertility, infertility, urogenital microbiota

İnfertiliteye Yeni Bir Bakış Açısı: Mikrobiyota

Öz

Dünya genelindeki toplam doğurganlık hızında hızlı bir düşüş görülmektedir. Artan infertilite oranları, bu durumun nedenleri arasında yer almakta olup çiftlerin %10-15’inin infertiliteden etkilendiği ifade edilmektedir. Genital enfeksiyonlar, over rezerv azlığı, yumurtlama düzensizliği, obezite gibi birçok faktör infertilite nedeni olarak gösterilirken son yıllarda yeni bir bakış açısıyla mikrobiyota da bu faktörler arasına dahil edilmiştir. Bağırsak mikrobiyotası, üreme durumunun gerçekleşmesini sağlayan ve düzeylerinin optimal olması oldukça önemli olan cinsiyet hormonlarını ve metabolitlerini düzenleyebilme yeteneğine sahiptir. Bağırsak mikrobiyotasının disbiyoza uğraması östrojen başta olmak üzere cinsiyet hormonlarının metabolizmasının bozulmasına neden olarak endometriozis, polikistik over sendromu, endometrial hiperplazi gibi çeşitli üreme sağlığı sorunlarına yol açabilmektedir. Kadın ve erkek genital organları, çeşitli mikroorganizmalar barındırırken baskın florayı Lactobacillus oluşturmaktadır ve bu baskınlık üreme sistemi sağlığı, fertilite ve sağlıklı gebelik ile ilişkilendirilmektedir. Erkek ürogenital sisteminde bulunan çeşitli mikroorganizmaların semen kalitesi ile ilişkili olduğu belirtilmekle birlikte erkek ürogenital mikrobiyotasının disbiyozunun enfeksiyonlara, sperm kalitesinde azalmaya ve çeşitli üreme bozukluklarına neden olduğu ifade edilmektedir. Mikrobiyotadaki olumsuz değişiklikler gebelik sürecinde abortus, ölü/preterm doğum, tekrarlayan implantasyon başarısızlığı, preeklampsi, gestasyonel diyabet ve diğer birçok olumsuz gebelik sonucu ile ilişkilendirilmektedir. Bu derlemenin amacı insan bağırsak ve ürogenital mikrobiyotası ile fertilite arasındaki ilişkiyi incelemektir.

Anahtar Kelimeler

Bağırsak mikrobiyotası, fertilite, infertilite, ürogenital mikrobiyota

Kaynakça

• Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The international glossary on infertility and fertility care. Fertil Steril. 2017 Sep;108(3):393-406. DOI: 10.1016/j. fertnstert.2017.06.005.
• Hacettepe Üniversitesi Nüfus Etütleri Enstitüsü. 2018 Türkiye Nüfus ve Sağlık Araştırması. Ankara; 2019. [cited 2023 Nov 22] Available from: http://www.sck.gov.tr/wp-content/uploads/2020/08/TNSA2018_ana_ Rapor.pdf.
• Güner ZB. Uzun ömürlülük riskinin sosyal güvenlik sistemi dengesine etkisi. Sosyal Güvence. 2015 Nov;7:58-82.
• worldbank.org [Internet]. World Development Indicators; 2023 [cited 2023 Nov 22]. Available from: https://databank.worldbank.org/reports. aspx?source=2&series=SP.DYN.TFRT.IN&country=WLD.
• Hacettepe Üniversitesi Nüfus Etütleri Enstitüsü. Türkiye’de Doğurganlık, Üreme Sağlığı ve Yaşlılık: 2008 Türkiye Nüfus ve Sağlık Araştırması İleri Analiz Çalışması. Ankara; 2010. [cited 2023 Nov 22] Available from: http://www.openaccess.hacettepe.edu.tr:8080/xmlui/ bitstream/handle/11655/23337/turkiyede_dogurganlik_ureme_ sagligi_yaslilik_160910.pdf?sequence=1.
• Serour GI, Serour AG. Ethical issues in infertility. Best Pract Res Clin Obstet Gynaecol. 2017 Aug;43:21-31. DOI: 10.1016/j. bpobgyn.2017.02.008.
• who.int [Internet]. World Health Organisation; 2018 [cited 2023 Nov 22]. Available from: https://www.who.int/health-topics/ infertility#tab=tab_1.
• Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012 Dec; 9(12):1001356. DOI: 10.1371/journal.pmed.1001356.
• Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem. 2018 Dec;62:2-10. DOI: 10.1016/j. clinbiochem.2018.03.012.
• Acet F, Şahin G, Tavmergen Göker EN, Tavmergen E. Mikrobiota ve infertilite. Türk Üreme Tıbbı ve Cerrahisi Dergisi. 2021 Feb;5(1):18-22. DOI: 10.24074/tjrms.2020-80464.
• Mutic AD, Jordan S, Edwards SM, Ferranti EP, Thul TA, Yang I. The postpartum maternal and newborn microbiomes. MCN Am J Matern Child Nurs. 2017 Nov/Dec;42(6):326-331. DOI: 10.1097/ NMC.0000000000000374.
• González A, Vázquez-Baeza Y, Knight R. SnapShot: the human microbiome. Cell. 2014 Jul;158(3):690-690. DOI: 10.1016/j. cell.2014.07.019.
• Jin Y, Wu S, Zeng Z, Fu Z. Effects of environmental pollutants on gut microbiota. Environ Pollut. 2017 Mar;222:1-9. DOI: 10.1016/j. envpol.2016.11.045.
• Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG. Minireview: Gut microbiota: the neglected endocrine organ. Mol Endocrinol. 2014 Aug;28(8):1221-38. DOI: 10.1210/me.2014-1108.
• Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec;444(7122):1027-31. DOI: 10.1038/ doğa05414.
• Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 2017 Sep;103:45-53. DOI: 10.1016/j.maturitas.2017.06.025.
• Muhleisen AL, Herbst-Kralovetz MM. Menopause and the vaginal microbiome. Maturitas. 2016 Sep;91:42-50. DOI: 10.1016/j. maturitas.2016.05.015.
• La Vignera S, Vicari E, Condorelli RA, D'Agata R, Calogero AE. Male accessory gland infection and sperm parameters (review). Int J Androl. 2011 Oct;34(5 Pt 2):330-47. DOI: 10.1111/j.1365-2605.2011.01200.x.
• Weng SL, Chiu CM, Lin FM, Huang WC, Liang C, Yang T, et al. Bacterial communities in semen from men of infertile couples: Metagenomic sequencing reveals relationships of seminal microbiota to semen quality. PLoS One. 2014 Oct;9(10):e110152. DOI: 10.1371/journal.pone.0110152.
• Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015 Apr;13:37. DOI: 10.1186/s12958-015-0032-1.
• Levine H, Jørgensen N, Martino-Andrade A, Mendiola J, Weksler-Derri D, Mindlis I, et al. Temporal trends in sperm count: A systematic review and meta-regression analysis. Hum Reprod Update. 2017 Nov;23(6):646- 659. DOI: 10.1093/humupd/dmx022.
• Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992 Sep;305(6854):609-13. DOI: 10.1136/bmj.305.6854.609.
• Splingart C, Frapsauce C, Veau S, Barthélémy C, Royère D, Guérif F. Semen variation in a population of fertile donors: evaluation in a French centre over a 34-year period. Int J Androl. 2012 Jun;35(3):467-74. DOI: 10.1111/j.1365-2605.2011.01229.x.
• Jung JH, Kim MH, Kim J, Baik SK, Koh SB, Park HJ, et al. Treatment of leukocytospermia in male infertility: A systematic review. World J Mens Health. 2016 Dec;34(3):165-172. DOI: 10.5534/wjmh.2016.34.3.165.
• Valcarce DG, Genovés S, Riesco MF, Martorell P, Herráez MP, Ramón D, et al. Probiotic administration improves sperm quality in asthenozoospermic human donors. Benef Microbes. 2017 Apr;8(2):193- 206. DOI: 10.3920/BM2016.0122.
• Lundy SD, Sangwan N, Parekh NV, Selvam MKP, Gupta S, McCaffrey P, et al. Functional and taxonomic dysbiosis of the gut, urine, and semen microbiomes in male infertility. Eur Urol. 2021 Jun;79(6):826-36. DOI: 10.1016/j.eururo.2021.01.014.
• Bajic P, Wolfe AJ. The microbiome of male infertility: paving the road ahead. Eur Urol. 2021 Jun;79(6):837-8. DOI: 10.1016/j.eururo.2021.02.009.
• Lundy SD, Sabanegh ES Jr. Varicocele management for infertility and pain: A systematic review. Arab J Urol. 2017 Dec;16(1):157-70. DOI: 10.1016/j.aju.2017.11.003.
• Hou D, Zhou X, Zhong X, Settles ML, Herring J, Wang L, et al. Microbiota of the seminal fluid from healthy and infertile men. Fertil Steril. 2013 Nov;100(5):1261-9. DOI: 10.1016/j.fertnstert.2013.07.1991.
• Akgül T, Doğantekin E, Ağras K. İdiyopatik erkek infertilitesinde probiyotiklerin yeri. Androl Bul. 2019 Dec;21:67-71. DOI: 10.24898/ tandro.2019.57442.
• Bashandy AES. Effect of fixed oil of Nigella sativa on male fertility in normal and hyperlipidemic rats. Int J Pharmacol. 2007 Jan;3:27-33. DOI: 10.3923/ijp.2007.27.33.
• De La Cruz JP, Quintero L, Villalobos MA, Sánchez de la Cuesta F. Lipid peroxidation and glutathione system in hyperlipemic rabbits: influence of olive oil administration. Biochim Biophys Acta. 2000 May;1485(1):36- 44. DOI: 10.1016/s1388-1981(00)00027-5.
• Brady LJ, Gallaher DD, Busta FF. The role of probiotic cultures in the prevention of colon cancer. J Nutr. 2000 Feb;130(2):410-4. DOI: 10.1093/ jn/130.2.410S.
• 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. 2017 May;5(3):439-44. DOI: 10.1111/andr.12336.
• Dallenbach-Hellweg G. Histopathology of the endometrium. Berlin, Heidelberg: Springer; 1981. 89-256 p.
• Moreno I, Simon C. Deciphering the effect of reproductive tract microbiota on human reproduction. Reprod Med Biol. 2018 Nov;18(1):40-50. DOI: 10.1002/rmb2.12249
• Tomaiuolo R, Veneruso I, Cariati F, D'Argenio V. Microbiota and human reproduction: The case of female infertility. High Throughput. 2020 May;9(2):12. DOI: 10.3390/ht9020012.
• Glycogen levels in undiluted genital fluid and their relationship to vaginal pH, estrogen, and progesterone. PLoS One. 2016 Apr;11(4):e0153553. DOI: 10.1371/journal.pone.0153553.
• Borges S, Silva J, Teixeira P. The role of lactobacilli and probiotics in maintaining vaginal health. Arch Gynecol Obstet. 2014 Mar;289(3):479- 89. DOI: 10.1007/s00404-013-3064-9.
• Santos CMA, Pires MCV, Leão TL, Hernández ZP, Rodriguez ML, Martins AKS, et al. Selection of lactobacillus strains as potential probiotics for vaginitis treatment. Microbiology. 2016 Jul;162(7):1195- 207. DOI: 10.1099/mic.0.000302.
• Machado D, Castro J, Palmeira-de-Oliveira A, Martinez-de-Oliveira J, Cerca N. Bacterial vaginosis biofilms: challenges to current therapies and emerging solutions. Front Microbiol. 2016 Jan;6:1528. DOI: 10.3389/ fmicb.2015.01528.
• Salah RM, Allam AM, Magdy AM, Mohamed ASh. Bacterial vaginosis and infertility: cause or association? Eur J Obstet Gynecol Reprod Biol. 2013 Mar;167(1):59-63. DOI: 10.1016/j.ejogrb.2012.10.031.
• Pelzer ES, Allan JA, Waterhouse MA, Ross T, Beagley KW, Knox CL. Microorganisms within human follicular fluid: effects on IVF. PLoS One. 2013 Mar;8(3):e59062. DOI: 10.1371/journal.pone.0059062.
• Miles SM, Hardy BL, Merrell DS. Investigation of the microbiota of the reproductive tract in women undergoing a total hysterectomy and bilateral salpingo-oopherectomy. Fertil Steril. 2017 Mar;107(3):813-20. e1. DOI: 10.1016/j.fertnstert.2016.11.028.
• Torcia MG. Interplay among vaginal microbiome, immune response and sexually transmitted viral infections. Int J Mol Sci. 2019 Jan;20(2):266-78. DOI: 10.3390/ijms20020266.
• Wee BA, Thomas M, Sweeney EL, Frentiu FD, Samios M, Ravel J, et al. A retrospective pilot study to determine whether the reproductive tract microbiota differs between women with a history of infertility and fertile women. Aust N Z J Obstet Gynaecol. 2018 Jun;58(3):341-8. DOI: 10.1111/she.12754.
• Moreno I, Codoñer FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazán J, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016 Dec;215(6):684-703. DOI: 10.1016/j.ajog.2016.09.075.
• Coulam CB, Bilal M, Salazar Garcia MD, Katukurundage D, Elazzamy H, Fernandez EF, et al. Prevalence of HHV-6 in endometrium from women with recurrent implantation failure. Am J Reprod Immunol. 2018 Jul;80(1):e12862. DOI: 10.1111/aji.12862.
• Graspeuntner S, Bohlmann MK, Gillmann K, Speer R, Kuenzel S, Mark H, et al. Microbiota-based analysis reveals specific bacterial traits and a novel strategy for the diagnosis of infectious infertility. PLoS One. 2018 Jan;13(1):e0191047. DOI: 10.1371/journal.pone.0191047.
• Campisciano G, Florian F, D'Eustacchio A, Stanković D, Ricci G, De Seta F, et al. Subclinical alteration of the cervical-vaginal microbiome in women with idiopathic infertility. J Cell Physiol. 2017 Jul;232(7):1681-8. DOI: 10.1002/jcp.25806.
• Koedooder R, Singer M, Schoenmakers S, Savelkoul PHM, Morré SA, de Jonge JD, et al. The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study. Hum Reprod. 2019 Jun;34(6):1042-54. DOI: 10.1093/ humrep/dez065.
• Shin JH, Park YH, Sim M, Kim SA, Joung H, Shin DM. Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome. Res Microbiol. 2019 Jun-Aug;170(4-5):192-201. DOI: 10.1016/j.resmic.2019.03.003.
• Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011 Feb;32(1):81-151. DOI: 10.1210/er.2010-0013.
• Pace F, Watnick PI. The interplay of sex steroids, the immune response, and the intestinal microbiota. Trends Microbiol. 2021 Sep;29(9):849-59. DOI: 10.1016/j.tim.2020.11.001.
• Pascale A, Marchesi N, Marelli C, Coppola A, Luzi L, Govoni S, et al. Microbiota and metabolic diseases. Endocrine. 2018 Sep;61(3):357-71. DOI: 10.1007/s12020-018-1605-5.
• Plottel CS, Blaser MJ. Microbiome and malignancy. Cell Host Microbe. 2011 Oct;10(4):324-35. DOI: 10.1016/j.chom.2011.10.003.
• He M, Gao J, Wu J, Zhou Y, Fu H, Ke S, et al. Host gender and androgen levels regulate gut bacterial taxa in pigs leading to sex-biased serum metabolite profiles. Front Microbiol. 2019 Jun;10:1359. DOI: 10.3389/ fmicb.2019.01359.
• Sato R, Suzuki T, Katayose Y, Miura K, Shiiba K, Miki Y, et al. Aromatase in colon carcinoma. Anticancer Res. 2012 Aug;32(8):3069-75.
• Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, Rolle-Kampczyk U, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013 Mar;339(6123):1084-8. DOI: 10.1126/science.1233521.
• Antwis RE, Edwards KL, Unwin B, Walker SL, Shultz S. Rare gut microbiota associated with breeding success, hormone metabolites and ovarian cycle phase in the critically endangered eastern black rhino. Microbiome. 2019 Feb;7(1):27-38. DOI: 10.1186/s40168-019-0639-0.
• Tremellen K, Pearce K. Dysbiosis of gut microbiota (DOGMA)--a novel theory for the development of polycystic ovarian syndrome. Med Hypotheses. 2012 Jul;79(1):104-12. DOI: 10.1016/j.mehy.2012.04.016.
• Nadal I, Santacruz A, Marcos A, Warnberg J, Garagorri JM, Moreno LA, et al. Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents. Int J Obes (Lond). 2009 Jul;33(7):758-67. DOI: 10.1038/ijo.2008.260.
• Charalampakis V, Tahrani AA, Helmy A, Gupta JK, Singhal R. Polycystic ovary syndrome and endometrial hyperplasia: an overview of the role of bariatric surgery in female fertility. Eur J Obstet Gynecol Reprod Biol. 2016 Dec;207:220-6. DOI: 10.1016/j.ejogrb.2016.10.001.
• Kaska L, Sledzinski T, Chomiczewska A, Dettlaff-Pokora A, Swierczynski J. Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome. World J Gastroenterol. 2016 Oct;22(39):8698-719. DOI: 10.3748/wjg.v22.i39.8698.
• Nagpal R, Shively CA, Register TC, Craft S, Yadav H. Gut microbiome- Mediterranean diet interactions in improving host health. F1000Res. 2019 May;8:699. DOI: 10.12688/f1000research.18992.1.
• Barber TM, Kabisch S, Pfeiffer AFH, Weickert MO. The Effects of the Mediterranean Diet on Health and Gut Microbiota. Nutrients. 2023 Apr;15(9):2150. DOI: 10.3390/nu15092150.
• Sukur G, Uysal F, Cinar O. High-fat diet induced obesity alters Dnmt1 and Dnmt3a levels and global DNA methylation in mouse ovary and testis. Histochem Cell Biol. 2023 Apr;159(4):339–52. DOI: 10.1007/ s00418-022-02173-2.
• Liu CY, Chang TC, Lin SH, Tsao CW. Is a Ketogenic Diet Superior to a High-Fat, High-Cholesterol Diet Regarding Testicular Function and Spermatogenesis? Front Nutr. 2022 Feb;9:805794. DOI: 10.3389/ fnut.2022.805794.