Highly diverse anaerobe-predominant vaginal microbiota among HIV-infected pregnant women in Zambia
Autoři:
Joan T. Price aff001; Bellington Vwalika aff002; Marcia Hobbs aff004; Julie A. E. Nelson aff005; Elizabeth M. Stringer aff001; Fei Zou aff006; Katelyn J. Rittenhouse aff001; Andrea Azcarate-Peril aff007; Margaret P. Kasaro aff003; Jeffrey S. A. Stringer aff001
Působiště autorů:
Division of Global Women’s Health, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America
aff001; Department of Obstetrics and Gynaecology, University of Zambia School of Medicine, Lusaka, Zambia
aff002; UNC Global Projects Zambia, Lusaka, Zambia
aff003; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America
aff004; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America
aff005; Department of Biostatistics, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, United States of America
aff006; Microbiome Core Facility, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
aff007
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0223128
Souhrn
Vaginal dysbiosis has been shown to increase the risk of some adverse birth outcomes. HIV infection may be associated with shifts in the vaginal microbiome. We characterized microbial communities in vaginal swabs collected between 16–20 gestational weeks in the Zambian Preterm Birth Prevention Study to investigate whether HIV and its treatment alter the microbiome in pregnancy. We quantified relative abundance and diversity of bacterial taxa by whole-genome shotgun sequencing and identified community state types (CST) by hierarchical clustering. Associations between exposures—HIV serostatus (HIV+ vs HIV-) and preconceptional ART (ART+ vs ART-)—and microbiome characteristics were tested with rank-sum, and by linear and logistic regression, accounting for sampling by inverse-probability weighting. Of 261 vaginal swabs, 256 (98%) had evaluable sequences; 98 (38%) were from HIV+ participants, 55 (56%) of whom had preconceptional ART exposure. Major CSTs were dominated by: L. crispatus (CST 1; 17%), L.] iners (CST 3; 32%), Gardnerella vaginalis (CST 4-I; 37%), G. vaginalis & Atopobium vaginae (CST 4-II; 5%), and other mixed anaerobes (CST 4-III; 9%). G. vaginalis was present in 95%; mean relative abundance was higher in HIV+ (0.46±0.29) compared to HIV- participants (0.35±0.33; rank-sum p = .01). Shannon diversity was higher in HIV+/ART+ (coeff 0.17; 95%CI (0.01,0.33), p = .04) and HIV+/ART- (coeff 0.37; 95%CI (0.19,0.55), p < .001) participants compared to HIV-. Anaerobe-dominant CSTs were more prevalent in HIV+/ART+ (63%, AOR 3.11; 95%CI: 1.48,6.55, p = .003) and HIV+/ART- (85%, AOR 7.59; 95%CI (2.80,20.6), p < .001) compared to HIV- (45%). Restricting the comparison to 111 women in either CST 3 (L. iners dominance) or CST 1 (L. crispatus dominance), CST 3 frequency was similar in HIV- (63%) and HIV+/ART- participants (67%, AOR 1.31; 95%CI: (0.25,6.90), p = .7), but higher in HIV+/ART+ (89%, AOR 6.44; 95%CI: (1.12,37.0), p = .04). Pregnant women in Zambia, particularly those with HIV, had diverse anaerobe-dominant vaginal microbiota.
Klíčová slova:
Pregnancy – Species diversity – Microbiome – Lactobacillus – Preterm birth – Assisted reproductive technology
Zdroje
1. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4680–7. doi: 10.1073/pnas.1002611107 20534435; PubMed Central PMCID: PMC3063603.
2. Borgdorff H, Tsivtsivadze E, Verhelst R, Marzorati M, Jurriaans S, Ndayisaba GF, et al. Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women. ISME J. 2014;8(9):1781–93. doi: 10.1038/ismej.2014.26 24599071; PubMed Central PMCID: PMC4139719.
3. Martin HL, Richardson BA, Nyange PM, Lavreys L, Hillier SL, Chohan B, et al. Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis. 1999;180(6):1863–8. doi: 10.1086/315127 10558942.
4. Ness RB, Kip KE, Hillier SL, Soper DE, Stamm CA, Sweet RL, et al. A cluster analysis of bacterial vaginosis-associated microflora and pelvic inflammatory disease. Am J Epidemiol. 2005;162(6):585–90. Epub 2005/08/12. doi: 10.1093/aje/kwi243 16093289.
5. Kimberlin DF, Andrews WW. Bacterial vaginosis: association with adverse pregnancy outcome. Semin Perinatol. 1998;22(4):242–50. Epub 1998/09/17. 9738988.
6. van Oostrum N, De Sutter P, Meys J, Verstraelen H. Risks associated with bacterial vaginosis in infertility patients: a systematic review and meta-analysis. Hum Reprod. 2013;28(7):1809–15. doi: 10.1093/humrep/det096 23543384.
7. Anahtar MN, Byrne EH, Doherty KE, Bowman BA, Yamamoto HS, Soumillon M, et al. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract. Immunity. 2015;42(5):965–76. doi: 10.1016/j.immuni.2015.04.019 25992865; PubMed Central PMCID: PMC4461369.
8. Zevin AS, Xie IY, Birse K, Arnold K, Romas L, Westmacott G, et al. Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract. PLoS Pathog. 2016;12(9):e1005889. doi: 10.1371/journal.ppat.1005889 27656899; PubMed Central PMCID: PMC5033340.
9. O'Hanlon DE, Moench TR, Cone RA. Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS One. 2013;8(11):e80074. doi: 10.1371/journal.pone.0080074 24223212; PubMed Central PMCID: PMC3819307.
10. Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS, Martin DH, et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med. 1995;333(26):1737–42. doi: 10.1056/NEJM199512283332604 7491137.
11. Chaim W, Mazor M, Leiberman JR. The relationship between bacterial vaginosis and preterm birth. A review. Arch Gynecol Obstet. 1997;259(2):51–8. 9059744.
12. Verstraelen H, Verhelst R, Claeys G, De Backer E, Temmerman M, Vaneechoutte M. Longitudinal analysis of the vaginal microflora in pregnancy suggests that L. crispatus promotes the stability of the normal vaginal microflora and that L. gasseri and/or L. iners are more conducive to the occurrence of abnormal vaginal microflora. BMC Microbiol. 2009;9:116. doi: 10.1186/1471-2180-9-116 19490622; PubMed Central PMCID: PMC2698831.
13. Nunn KL, Wang YY, Harit D, Humphrys MS, Ma B, Cone R, et al. Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota. MBio. 2015;6(5):e01084–15. doi: 10.1128/mBio.01084-15 26443453; PubMed Central PMCID: PMC4611035.
14. Kindinger LM, Bennett PR, Lee YS, Marchesi JR, Smith A, Cacciatore S, et al. The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk. Microbiome. 2017;5(1):6. doi: 10.1186/s40168-016-0223-9 28103952; PubMed Central PMCID: PMC5244550.
15. Kharsany AB, Frohlich JA, Yende-Zuma N, Mahlase G, Samsunder N, Dellar RC, et al. Trends in HIV Prevalence in Pregnant Women in Rural South Africa. J Acquir Immune Defic Syndr. 2015;70(3):289–95. doi: 10.1097/QAI.0000000000000761 26186507; PubMed Central PMCID: PMC5056320.
16. Wedi CO, Kirtley S, Hopewell S, Corrigan R, Kennedy SH, Hemelaar J. Perinatal outcomes associated with maternal HIV infection: a systematic review and meta-analysis. Lancet HIV. 2016;3(1):e33–48. doi: 10.1016/S2352-3018(15)00207-6 26762992.
17. Uthman OA, Nachega JB, Anderson J, Kanters S, Mills EJ, Renaud F, et al. Timing of initiation of antiretroviral therapy and adverse pregnancy outcomes: a systematic review and meta-analysis. Lancet HIV. 2017;4(1):e21–e30. doi: 10.1016/S2352-3018(16)30195-3 27864000.
18. Doyle R, Gondwe A, Fan YM, Maleta K, Ashorn P, Klein N, et al. Lactobacillus-deficient vaginal microbiota dominate post-partum women in rural Malawi. Appl Environ Microbiol. 2018. doi: 10.1128/AEM.02150-17 29305501; PubMed Central PMCID: PMC5835753.
19. Bisanz JE, Enos MK, PrayGod G, Seney S, Macklaim JM, Chilton S, et al. Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt. Appl Environ Microbiol. 2015;81(15):4965–75. doi: 10.1128/AEM.00780-15 25979893; PubMed Central PMCID: PMC4495201.
20. Frank DN, Manigart O, Leroy V, Meda N, Valea D, Zhang W, et al. Altered vaginal microbiota are associated with perinatal mother-to-child transmission of HIV in African women from Burkina Faso. J Acquir Immune Defic Syndr. 2012;60(3):299–306. doi: 10.1097/QAI.0b013e31824e4bdb 22343176; PubMed Central PMCID: PMC6384121.
21. Taha TE, Gray RH, Kumwenda NI, Hoover DR, Mtimavalye LA, Liomba GN, et al. HIV infection and disturbances of vaginal flora during pregnancy. J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20(1):52–9. 9928730.
22. Short CS, Brown R, Quinlan RA, Shattock RJ, Bennett PR, Taylor G, et al. The vaginal microbiome in pregnancy differs by HIV status, ART exposure, and class. Conference on Retroviruses and Opportunistic Infections; 4–7 March, 2018; Boston, MA.
23. Cottrell ML, Yang KH, Prince HM, Sykes C, White N, Malone S, et al. A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine. J Infect Dis. 2016;214(1):55–64. doi: 10.1093/infdis/jiw077 26917574; PubMed Central PMCID: PMC4907409.
24. Dumond JB, Yang KH, Kendrick R, Reddy YS, Kashuba AD, Troiani L, et al. Pharmacokinetic Modeling of Lamivudine and Zidovudine Triphosphates Predicts Differential Pharmacokinetics in Seminal Mononuclear Cells and Peripheral Blood Mononuclear Cells. Antimicrob Agents Chemother. 2015;59(10):6395–401. doi: 10.1128/AAC.01148-15 26239974; PubMed Central PMCID: PMC4576057.
25. Dumond JB, Yeh RF, Patterson KB, Corbett AH, Jung BH, Rezk NL, et al. Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis. AIDS. 2007;21(14):1899–907. doi: 10.1097/QAD.0b013e328270385a 17721097; PubMed Central PMCID: PMC2862268.
26. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9(4):357–9. doi: 10.1038/nmeth.1923 22388286; PubMed Central PMCID: PMC3322381.
27. Rognes T, Flouri T, Nichols B, Quince C, Mahe F. VSEARCH: a versatile open source tool for metagenomics. PeerJ. 2016;4:e2584. doi: 10.7717/peerj.2584 27781170; PubMed Central PMCID: PMC5075697.
28. Lemos LN, Fulthorpe RR, Triplett EW, Roesch LF. Rethinking microbial diversity analysis in the high throughput sequencing era. J Microbiol Methods. 2011;86(1):42–51. doi: 10.1016/j.mimet.2011.03.014 21457733.
29. Judkins DR. Fay's method for variance estimation. Journal of Official Statistics. 1990;6:223–239.
30. Leo Lahti, Sudarshan Shetty et al. Tools for microbiome analysis in R. Version 1.1.10013. URL: http://microbiome.github.com/microbiome.
31. McMurdie PJ, Holmes S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One. 2013;8(4):e61217. Epub 2013/05/01. doi: 10.1371/journal.pone.0061217 23630581; PubMed Central PMCID: PMC3632530.
32. Castillo MC, Fuseini NM, Rittenhouse K, Price JT, Freeman BL, Mwape H, et al. The Zambian Preterm Birth Prevention Study (ZAPPS): Cohort characteristics at enrollment. Gates Open Res. 2018;2:25. doi: 10.12688/gatesopenres.12820.3 30706053; PubMed Central PMCID: PMC6350406.
33. Hummelen R, Fernandes AD, Macklaim JM, Dickson RJ, Changalucha J, Gloor GB, et al. Deep sequencing of the vaginal microbiota of women with HIV. PLoS One. 2010;5(8):e12078. doi: 10.1371/journal.pone.0012078 20711427; PubMed Central PMCID: PMC2920804.
34. McClelland RS, Lingappa JR, Srinivasan S, Kinuthia J, John-Stewart GC, Jaoko W, et al. Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study. Lancet Infect Dis. 2018;18(5):554–64. doi: 10.1016/S1473-3099(18)30058-6 29396006; PubMed Central PMCID: PMC6445552.
35. Gosmann C, Anahtar MN, Handley SA, Farcasanu M, Abu-Ali G, Bowman BA, et al. Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women. Immunity. 2017;46(1):29–37. doi: 10.1016/j.immuni.2016.12.013 28087240; PubMed Central PMCID: PMC5270628.
36. Srinivasan S, Richardson BA, Wallis J, Fiedler TL, Dezzuti CS, Chirenje MZ, et al. Vaginal microbiota and HIV acquisition risk among African women. Conference on Retroviruses and Opportunistic Infections; 4–7 March, 2018; Boston, MA.
37. Leitich H, Kiss H. Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol. 2007;21(3):375–90. doi: 10.1016/j.bpobgyn.2006.12.005 17241817.
38. Romero R, Hassan SS, Gajer P, Tarca AL, Fadrosh DW, Bieda J, et al. The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term. Microbiome. 2014;2:18. doi: 10.1186/2049-2618-2-18 24987521; PubMed Central PMCID: PMC4066267.
39. Callahan BJ, DiGiulio DB, Goltsman DSA, Sun CL, Costello EK, Jeganathan P, et al. Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women. Proc Natl Acad Sci U S A. 2017;114(37):9966–71. doi: 10.1073/pnas.1705899114 28847941; PubMed Central PMCID: PMC5604014.
40. Parnell LA, Briggs CM, Mysorekar IU. Maternal microbiomes in preterm birth: Recent progress and analytical pipelines. Semin Perinatol. 2017;41(7):392–400. doi: 10.1053/j.semperi.2017.07.010 28823578; PubMed Central PMCID: PMC6280966.
41. Ravel J, Brotman RM. Translating the vaginal microbiome: gaps and challenges. Genome Med. 2016;8(1):35. doi: 10.1186/s13073-016-0291-2 27036316; PubMed Central PMCID: PMC4818402.
42. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14. Published 2012 Jun 13. doi: 10.1038/nature11234 22699609
43. Ranjan R, Rani A, Metwally A, McGee HS, Perkins DL. Analysis of the microbiome: Advantages of whole genome shotgun versus 16S amplicon sequencing. Biochem Biophys Res Commun. 2016;469(4):967–77. doi: 10.1016/j.bbrc.2015.12.083 26718401; PubMed Central PMCID: PMC4830092.
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