Life History Recorded in the Vagino-cervical Microbiome Along with Multi-omes.

Zhuye Jie, Chen Chen, Lilan Hao, Fei Li, Liju Song, Xiaowei Zhang, Jie Zhu, Liu Tian, Xin Tong, Kaiye Cai, Zhe Zhang, Yanmei Ju, Xinlei Yu, Ying Li, Hongcheng Zhou, Haorong Lu, Xuemei Qiu, Qiang Li, Yunli Liao, Dongsheng Zhou, Heng Lian, Yong Zuo, Xiaomin Chen, Weiqiao Rao, Yan Ren, Yuan Wang, Jin Zi, Rong Wang, Na Liu, Jinghua Wu, Wei Zhang, Xiao Liu, Yang Zong, Weibin Liu, Liang Xiao, Yong Hou, Xun Xu, Huanming Yang, Jian Wang, Karsten Kristiansen, Huijue Jia
Author Information
  1. Zhuye Jie: BGI-Shenzhen, Shenzhen 518083, China; Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen 518083, China; Department of Biology, University of Copenhagen, Copenhagen DK-2100, Denmark.
  2. Chen Chen: BGI-Shenzhen, Shenzhen 518083, China; Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen 518083, China; Department of Biology, University of Copenhagen, Copenhagen DK-2100, Denmark. Electronic address: chenchen1@genomics.cn.
  3. Lilan Hao: BGI-Shenzhen, Shenzhen 518083, China.
  4. Fei Li: BGI-Shenzhen, Shenzhen 518083, China.
  5. Liju Song: BGI-Shenzhen, Shenzhen 518083, China.
  6. Xiaowei Zhang: BGI-Shenzhen, Shenzhen 518083, China.
  7. Jie Zhu: BGI-Shenzhen, Shenzhen 518083, China.
  8. Liu Tian: BGI-Shenzhen, Shenzhen 518083, China.
  9. Xin Tong: BGI-Shenzhen, Shenzhen 518083, China.
  10. Kaiye Cai: BGI-Shenzhen, Shenzhen 518083, China; Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen 518083, China.
  11. Zhe Zhang: BGI-Shenzhen, Shenzhen 518083, China.
  12. Yanmei Ju: BGI-Shenzhen, Shenzhen 518083, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China.
  13. Xinlei Yu: BGI-Shenzhen, Shenzhen 518083, China.
  14. Ying Li: BGI-Shenzhen, Shenzhen 518083, China.
  15. Hongcheng Zhou: China National Genebank, BGI-Shenzhen, Shenzhen 518120, China.
  16. Haorong Lu: China National Genebank, BGI-Shenzhen, Shenzhen 518120, China.
  17. Xuemei Qiu: BGI-Shenzhen, Shenzhen 518083, China.
  18. Qiang Li: BGI-Shenzhen, Shenzhen 518083, China.
  19. Yunli Liao: BGI-Shenzhen, Shenzhen 518083, China.
  20. Dongsheng Zhou: BGI-Shenzhen, Shenzhen 518083, China.
  21. Heng Lian: BGI-Shenzhen, Shenzhen 518083, China.
  22. Yong Zuo: BGI-Shenzhen, Shenzhen 518083, China.
  23. Xiaomin Chen: BGI-Shenzhen, Shenzhen 518083, China.
  24. Weiqiao Rao: BGI-Shenzhen, Shenzhen 518083, China.
  25. Yan Ren: BGI-Shenzhen, Shenzhen 518083, China.
  26. Yuan Wang: BGI-Shenzhen, Shenzhen 518083, China.
  27. Jin Zi: BGI-Shenzhen, Shenzhen 518083, China.
  28. Rong Wang: BGI-Shenzhen, Shenzhen 518083, China.
  29. Na Liu: BGI-Shenzhen, Shenzhen 518083, China.
  30. Jinghua Wu: BGI-Shenzhen, Shenzhen 518083, China.
  31. Wei Zhang: BGI-Shenzhen, Shenzhen 518083, China.
  32. Xiao Liu: BGI-Shenzhen, Shenzhen 518083, China.
  33. Yang Zong: BGI-Shenzhen, Shenzhen 518083, China.
  34. Weibin Liu: BGI-Shenzhen, Shenzhen 518083, China.
  35. Liang Xiao: BGI-Shenzhen, Shenzhen 518083, China; Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen 518083, China; BGI-Qingdao, BGI-Shenzhen, Qingdao 266555, China.
  36. Yong Hou: BGI-Shenzhen, Shenzhen 518083, China.
  37. Xun Xu: BGI-Shenzhen, Shenzhen 518083, China.
  38. Huanming Yang: BGI-Shenzhen, Shenzhen 518083, China; James D. Watson Institute of Genome Sciences, Hangzhou 310058, China.
  39. Jian Wang: BGI-Shenzhen, Shenzhen 518083, China; James D. Watson Institute of Genome Sciences, Hangzhou 310058, China.
  40. Karsten Kristiansen: BGI-Shenzhen, Shenzhen 518083, China; Department of Biology, University of Copenhagen, Copenhagen DK-2100, Denmark; BGI-Qingdao, BGI-Shenzhen, Qingdao 266555, China.
  41. Huijue Jia: BGI-Shenzhen, Shenzhen 518083, China; Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen 518083, China. Electronic address: jiahuijue@genomics.cn.

Abstract

The vagina contains at least a billion microbial cells, dominated by lactobacilli. Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age, as well as cervical, fecal, and salivary samples from a second cohort of 632 women. Factors such as pregnancyhistory, delivery history, cesarean section, and breastfeeding were all more important than menstrual cycle in shaping the microbiome, and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data. Greater proportion of Bifidobacterium breve was seen with older age at sexual debut. The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history. Potential markers for lack of menstrual regularity, heavy flow, dysmenorrhea, and contraceptives were also identified. Lactobacilli were rare during breastfeeding or post-menopause. Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome. Gut and salivary microbiomes, plasma vitamins, metals, amino acids, and hormones showed associations with the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Keywords

References

  1. Yi Chuan. 2020 Aug 20;42(8):799-809 [PMID: 32952115]
  2. Sci Rep. 2019 May 2;9(1):6838 [PMID: 31048728]
  3. Genomics Proteomics Bioinformatics. 2021 Aug;19(4):584-589 [PMID: 34175476]
  4. Nat Rev Microbiol. 2016 Aug;14(8):508-22 [PMID: 27396567]
  5. ISME J. 2014 Sep;8(9):1781-93 [PMID: 24599071]
  6. Nat Methods. 2012 Jul 15;9(8):796-804 [PMID: 22796662]
  7. PLoS One. 2012;7(12):e49965 [PMID: 23226503]
  8. Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):11060-5 [PMID: 26283357]
  9. Nat Methods. 2012 Jun 10;9(8):811-4 [PMID: 22688413]
  10. Virulence. 2017 Apr 3;8(3):342-351 [PMID: 27657355]
  11. Antimicrob Agents Chemother. 2010 Jan;54(1):60-4 [PMID: 19805556]
  12. Nat Rev Microbiol. 2018 Mar;16(3):143-155 [PMID: 29332945]
  13. Nature. 2012 Jun 13;486(7402):207-14 [PMID: 22699609]
  14. Appl Environ Microbiol. 2003 Aug;69(8):4421-30 [PMID: 12902225]
  15. Cell. 2009 Jul 10;138(1):30-50 [PMID: 19596234]
  16. EBioMedicine. 2017 May;19:39-48 [PMID: 28438506]
  17. Gut. 2018 Sep;67(9):1614-1625 [PMID: 29760169]
  18. Sci Transl Med. 2012 May 2;4(132):132ra52 [PMID: 22553250]
  19. Genetics. 2015 Oct;201(2):459-72 [PMID: 26297338]
  20. Gigascience. 2018 Oct 1;7(10): [PMID: 30192933]
  21. Probiotics Antimicrob Proteins. 2019 Dec;11(4):1145-1154 [PMID: 30014348]
  22. Sci Rep. 2014 May 30;4:5136 [PMID: 24875844]
  23. Front Microbiol. 2018 Oct 08;9:2181 [PMID: 30349508]
  24. Am J Obstet Gynecol. 2019 Aug;221(2):146.e1-146.e23 [PMID: 31055031]
  25. Nat Med. 2019 Jun;25(6):1012-1021 [PMID: 31142849]
  26. PLoS One. 2013;8(3):e59062 [PMID: 23554970]
  27. Cell Rep. 2020 May 26;31(8):107674 [PMID: 32460009]
  28. Nature. 2012 Jun 13;486(7402):215-21 [PMID: 22699610]
  29. Nat Rev Microbiol. 2013 Apr;11(4):227-38 [PMID: 23435359]
  30. Cell. 2016 Nov 3;167(4):1125-1136.e8 [PMID: 27814509]
  31. Annu Rev Microbiol. 2012;66:371-89 [PMID: 22746335]
  32. J Matern Fetal Neonatal Med. 2019 Aug;32(16):2702-2710 [PMID: 29478370]
  33. J Infect Dis. 2012 May 15;205(10):1580-8 [PMID: 22448002]
  34. Genome Med. 2016 Nov 25;8(1):122 [PMID: 27884207]
  35. Nature. 2019 Aug;572(7769):329-334 [PMID: 31367035]
  36. Nat Med. 2019 Jun;25(6):1001-1011 [PMID: 31142850]
  37. Immunity. 2017 Jan 17;46(1):29-37 [PMID: 28087240]
  38. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4688-95 [PMID: 21059957]
  39. Am J Obstet Gynecol. 2013 Apr;208(4):321.e1-9 [PMID: 23313311]
  40. Gigascience. 2018 May 1;7(5): [PMID: 29762673]
  41. Science. 2020 Oct 2;370(6512):50-56 [PMID: 33004510]
  42. Sci Transl Med. 2014 May 21;6(237):237ra65 [PMID: 24848255]
  43. Nat Commun. 2017 Oct 17;8(1):875 [PMID: 29042534]
  44. Nature. 2017 Oct 5;550(7674):61-66 [PMID: 28953883]
  45. J Reprod Immunol. 2013 Sep;99(1-2):69-79 [PMID: 23972717]
  46. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4680-7 [PMID: 20534435]
  47. Nature. 2012 Oct 4;490(7418):55-60 [PMID: 23023125]
  48. J Med Microbiol. 1991 Dec;35(6):363-6 [PMID: 1721655]
  49. Nat Microbiol. 2017 Apr 25;2:17057 [PMID: 28440276]
  50. PLoS One. 2011 Mar 09;6(3):e17288 [PMID: 21408061]
  51. Microbiology (Reading). 2010 Dec;156(Pt 12):3635-3644 [PMID: 20705667]
  52. Nat Med. 2015 Aug;21(8):895-905 [PMID: 26214836]
  53. Biochem Biophys Res Commun. 2018 Nov 2;505(3):910-916 [PMID: 30309659]
  54. Nat Biotechnol. 2014 Aug;32(8):822-8 [PMID: 24997787]
  55. Gigascience. 2018 Mar 1;7(3):1-8 [PMID: 29293960]
  56. Nat Biotechnol. 2014 Aug;32(8):834-41 [PMID: 24997786]
  57. N Engl J Med. 2005 Nov 3;353(18):1899-911 [PMID: 16267321]
  58. Cell. 2013 Mar 28;153(1):240-52 [PMID: 23540701]
  59. Cell Host Microbe. 2018 Dec 12;24(6):857-865.e4 [PMID: 30503510]
  60. FEMS Microbiol Rev. 2013 Sep;37(5):762-92 [PMID: 23789590]
  61. Front Microbiol. 2018 Aug 22;9:2007 [PMID: 30186281]
  62. Genome Biol. 2012 Apr 16;13(9):R79 [PMID: 23013615]
  63. Sci Rep. 2017 Sep 11;7(1):11200 [PMID: 28894161]
  64. Nat Commun. 2017 Oct 10;8(1):845 [PMID: 29018189]
  65. Microbiome. 2018 Feb 27;6(1):43 [PMID: 29482661]
  66. Cell. 2016 Jan 28;164(3):337-40 [PMID: 26824647]
  67. J Perinatol. 2019 Jun;39(6):824-836 [PMID: 30858609]
  68. Mucosal Immunol. 2018 Mar;11(2):380-393 [PMID: 28745328]
  69. Database (Oxford). 2020 Jan 1;2020: [PMID: 32705130]

MeSH Term

Humans
Female
Pregnancy
RNA, Ribosomal, 16S
Cesarean Section
Vagina
Microbiota
Lactobacillus

Chemicals

RNA, Ribosomal, 16S

Links to CNCB-NGDC Resources

Word Cloud

Created with Highcharts 10.0.0microbiomehistoryvagino-cervicallactobacillishotgunsequencingcervicalfecalsamplescohortwomenreproductiveagesalivarybreastfeedingmenstrualVagino-cervicalvaginacontainsleastbillionmicrobialcellsdominatedperformmetagenomic516Chinesewellsecond632FactorspregnancyhistorydeliverycesareansectionimportantcycleshapinginformationnecessarytryinginterpretdifferencesdataGreaterproportionBifidobacteriumbreveseenoldersexualdebutrelativeabundanceespeciallyLactobacilluscrispatusnegativelyassociatedpregnancyPotentialmarkerslackregularityheavyflowdysmenorrheacontraceptivesalsoidentifiedLactobacillirarepost-menopausefeaturesmoodfluctuationsfacialspecklespotentiallypredictedGutmicrobiomesplasmavitaminsmetalsaminoacidshormonesshowedassociationsresultsofferunprecedentedglimpsemicrobiotafemaletractcallinternationalcollaborationsbetterunderstandlong-termhealthimpactsettingsinfectionpre-termbirthLifeHistoryRecordedMicrobiomeAlongMulti-omesBreastfeedingDeliveryMetagenomicPregnancy

Similar Articles

Cited By