Associations between dietary micronutrient intake and molecular-Bacterial Vaginosis

Susan Tuddenham, Khalil G Ghanem, Laura E Caulfield, Alisha J Rovner, Courtney Robinson, Rupak Shivakoti, Ryan Miller, Anne Burke, Catherine Murphy, Jacques Ravel, Rebecca M Brotman, Susan Tuddenham, Khalil G Ghanem, Laura E Caulfield, Alisha J Rovner, Courtney Robinson, Rupak Shivakoti, Ryan Miller, Anne Burke, Catherine Murphy, Jacques Ravel, Rebecca M Brotman

Abstract

Objectives: Bacterial vaginosis (BV), a clinical condition characterized by decreased vaginal Lactobacillus spp., is difficult to treat. We examined associations between micronutrient intake and a low-Lactobacillus vaginal microbiota as assessed by molecular methods (termed "molecular-BV").

Methods: This cross-sectional analysis utilized data collected at the baseline visit of the Hormonal Contraception Longitudinal Study, a cohort of reproductive-aged women followed over 2 years while initiating or ceasing hormonal contraception (HC). The Block Brief 2000 Food Frequency Questionnaire was administered and micronutrient intakes were ranked. Vaginal microbiota composition was assessed using 16S rRNA gene amplicon sequencing and clustered into community state types (CSTs) based on the types and relative abundance of bacteria detected. Associations between the lowest estimated quartile intake of nutrients and having a low-Lactobacillus CST (molecular-BV) were evaluated by logistic regression. Separate models were built for each nutrient controlling for age, body mass index, behavioral factors, HC use and total energy intake. We also conducted a literature review of existing data on associations between micronutrient intakes and BV.

Results: Samples from 104 women were included in this analysis. Their mean age was 25.8 years (SD 4.3), 29.8% were African American, 48.1% were using HC, and 25% had molecular-BV. In adjusted multivariable analyses, the lowest quartile of betaine intake was associated with an increased odds of molecular-BV (aOR 9.2, p value < 0.01, [CI 2.4-35.0]).

Conclusions: This is the first study to assess the association between estimated micronutrient intake and molecular-BV. Lower energy-adjusted intake of betaine was associated with an increased risk of molecular-BV. Betaine might have direct effects on the vaginal microenvironment or may be mediated through the gut microbiota. Additional research is needed to determine reproducibility of this finding and whether improved intake of select micronutrients such as betaine decreases the risk of BV and its sequelae.

Keywords: Bacterial Vaginosis; Betaine; Food frequency questionnaire; Vaginal microbiome.

Conflict of interest statement

The authors declare that they do not have any competing interests. Susan Tuddenham is a consultant for Biofire Diagnostics.

Figures

Fig. 1
Fig. 1
Heatmap of 104 vaginal microbiota, grouped into Community State Types (CSTs) based on bacterial composition and relative abundance

References

    1. Coleman JS, Gaydos CA. Molecular Diagnosis of Bacterial Vaginosis: an Update. J Clin Microbiol. 2018;56:9. doi: 10.1128/JCM.00342-18.
    1. Brotman RM, Klebanoff MA, Nansel TR, Yu KF, Andrews WW, Zhang J, et al. Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection. J Infect Dis. 2010;202(12):1907–1915. doi: 10.1086/657320.
    1. 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):1863–1868. doi: 10.1086/315127.
    1. 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.
    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):4680–4687. doi: 10.1073/pnas.1002611107.
    1. McKinnon LR, Achilles SL, Bradshaw CS, Burgener A, Crucitti T, Fredricks DN, et al. The evolving facets of bacterial Vaginosis: implications for HIV transmission. AIDS Res Hum Retrovir. 2019;35(3):219–228. doi: 10.1089/aid.2018.0304.
    1. Bradshaw CS, Morton AN, Hocking J, Garland SM, Morris MB, Moss LM, et al. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis. 2006;193(11):1478–1486. doi: 10.1086/503780.
    1. Moore KR, Harmon QE, Baird DD. Serum 25-Hydroxyvitamin D and risk of self-reported bacterial Vaginosis in a prospective cohort study of young African American women. J Women’s Health (Larchmt) 2018;27(10):1278–1284. doi: 10.1089/jwh.2017.6804.
    1. Akoh CC, Pressman EK, Cooper E, Queenan RA, Pillittere J, O’Brien KO. Low vitamin D is associated with infections and Proinflammatory cytokines during pregnancy. Reprod Sci. 2018;25(3):414–423. doi: 10.1177/1933719117715124.
    1. Brabin L, Roberts SA, Gies S, Nelson A, Diallo S, Stewart CJ, et al. Effects of long-term weekly iron and folic acid supplementation on lower genital tract infection - a double blind, randomised controlled trial in Burkina Faso. BMC Med. 2017;15(1):206. doi: 10.1186/s12916-017-0967-5.
    1. Turner AN, Carr Reese P, Chen PL, Kwok C, Jackson RD, Klebanoff MA, et al. Serum vitamin D status and bacterial vaginosis prevalence and incidence in Zimbabwean women. Am J Obstet Gynecol. 2016;215(3):332 e1–332e10. doi: 10.1016/j.ajog.2016.02.045.
    1. Taheri M, Baheiraei A, Foroushani AR, Nikmanesh B, Modarres M. Treatment of vitamin D deficiency is an effective method in the elimination of asymptomatic bacterial vaginosis: a placebo-controlled randomized clinical trial. Indian J Med Res. 2015;141(6):799–806. doi: 10.4103/0971-5916.160707.
    1. Turner AN, Carr Reese P, Fields KS, Anderson J, Ervin M, Davis JA, et al. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis. Am J Obstet Gynecol. 2014;211(5):479 e1–479e13. doi: 10.1016/j.ajog.2014.06.023.
    1. Klebanoff MA, Turner AN. Bacterial vaginosis and season, a proxy for vitamin D status. Sex Transm Dis. 2014;41(5):295–299. doi: 10.1097/OLQ.0000000000000124.
    1. Thoma ME, Klebanoff MA, Rovner AJ, Nansel TR, Neggers Y, Andrews WW, et al. Bacterial vaginosis is associated with variation in dietary indices. J Nutr. 2011;141(9):1698–1704. doi: 10.3945/jn.111.140541.
    1. Hensel KJ, Randis TM, Gelber SE, Ratner AJ. Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis. Am J Obstet Gynecol. 2011;204(1):41 e1–41 e9. doi: 10.1016/j.ajog.2010.08.013.
    1. French AL, Adeyemi OM, Agniel DM, Evans CT, Yin MT, Anastos K, et al. The association of HIV status with bacterial vaginosis and vitamin D in the United States. J Women's Health (Larchmt) 2011;20(10):1497–1503. doi: 10.1089/jwh.2010.2685.
    1. Dunlop AL, Taylor RN, Tangpricha V, Fortunato S, Menon R. Maternal vitamin D, folate, and polyunsaturated fatty acid status and bacterial vaginosis during pregnancy. Infect Dis Obstet Gynecol. 2011;2011:216217. doi: 10.1155/2011/216217.
    1. Christian P, Labrique AB, Ali H, Richman MJ, Wu L, Rashid M, et al. Maternal vitamin a and beta-carotene supplementation and risk of bacterial vaginosis: a randomized controlled trial in rural Bangladesh. Am J Clin Nutr. 2011;94(6):1643–1649. doi: 10.3945/ajcn.111.019059.
    1. Bodnar LM, Krohn MA, Simhan HN. Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. J Nutr. 2009;139(6):1157–1161. doi: 10.3945/jn.108.103168.
    1. Tohill BC, Heilig CM, Klein RS, Rompalo A, Cu-Uvin S, Piwoz EG, et al. Nutritional biomarkers associated with gynecological conditions among US women with or at risk of HIV infection. Am J Clin Nutr. 2007;85(5):1327–1334. doi: 10.1093/ajcn/85.5.1327.
    1. Neggers YH, Nansel TR, Andrews WW, Schwebke JR, Yu KF, Goldenberg RL, et al. Dietary intake of selected nutrients affects bacterial vaginosis in women. J Nutr. 2007;137(9):2128–2133. doi: 10.1093/jn/137.9.2128.
    1. Verstraelen H, Delanghe J, Roelens K, Blot S, Claeys G, Temmerman M. Subclinical iron deficiency is a strong predictor of bacterial vaginosis in early pregnancy. BMC Infect Dis. 2005;5:55. doi: 10.1186/1471-2334-5-55.
    1. Belec L, Mbopi-Keou FX, Roubache JF, Mayaud P, Paul JL, Gresenguet G. Vitamin a deficiency and genital tract infections in women living in Central Africa. J Acquir Immune Defic Syndr. 2002;29(2):203–204. doi: 10.1097/00042560-200202010-00016.
    1. Delgado C, Ward P, Chertow GM, Storer L, Dalrymple L, Block T, et al. Calibration of the brief food frequency questionnaire among patients on dialysis. J Ren Nutr. 2014;24(3):151–156. doi: 10.1053/j.jrn.2013.12.004.
    1. Holm JB HM, Robinson CK, Settles ML, Ott S, Fu L, Yang HM, Gajer P, McComb E, Ghanem K, Brotman R, Ravel J. Ultra-high throughput multiplexing and sequencing of >500 bp amplicon regions on the Illumina HiSeq 2500 platform. 2018.
    1. Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581–583. doi: 10.1038/nmeth.3869.
    1. Wang Q, Garrity GM, Tiedje JM, Cole JR. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007;73(16):5261–5267. doi: 10.1128/AEM.00062-07.
    1. Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013;41(Database issue):D590–D596.
    1. Mayer BT, Srinivasan S, Fiedler TL, Marrazzo JM, Fredricks DN, Schiffer JT. Rapid and profound shifts in the vaginal microbiota following antibiotic treatment for bacterial Vaginosis. J Infect Dis. 2015;212(5):793–802. doi: 10.1093/infdis/jiv079.
    1. van Houdt R, Ma B, Bruisten SM, Speksnijder A, Ravel J, de Vries HJC. Lactobacillus iners-dominated vaginal microbiota is associated with increased susceptibility to chlamydia trachomatis infection in Dutch women: a case-control study. Sex Transm Infect. 2018;94(2):117–123. doi: 10.1136/sextrans-2017-053133.
    1. Petricevic L, Domig KJ, Nierscher FJ, Sandhofer MJ, Fidesser M, Krondorfer I, et al. Characterisation of the vaginal Lactobacillus microbiota associated with preterm delivery. Sci Rep. 2014;4:5136. doi: 10.1038/srep05136.
    1. Wang H, Li S, Fang S, Yang X, Feng J. Betaine Improves Intestinal Functions by Enhancing Digestive Enzymes, Ameliorating Intestinal Morphology, and Enriching Intestinal Microbiota in High-salt stressed Rats. Nutrients. 2018;10:7.
    1. Metzler-Zebeli BU, Ratriyanto A, Jezierny D, Sauer N, Eklund M, Mosenthin R. Effects of betaine, organic acids and inulin as single feed additives or in combination on bacterial populations in the gastrointestinal tract of weaned pigs. Arch Anim Nutr. 2009;63(6):427–441. doi: 10.1080/17450390903299190.
    1. Craig SA. Betaine in human nutrition. Am J Clin Nutr. 2004;80(3):539–549. doi: 10.1093/ajcn/80.3.539.
    1. Kets E, de Bont J. Protective effect of betaine on survival of Lactobacillus plantarum subjected to drying. FEMS Microbiol Lett. 1994;116:251–256. doi: 10.1111/j.1574-6968.1994.tb06711.x.
    1. Zou H, Wu Z, Xian M, Liu H, Cheng T, Cao Y. Not only osmoprotectant: betaine increased lactate dehydrogenase activity and L-lactate production in lactobacilli. Bioresour Technol. 2013;148:591–595. doi: 10.1016/j.biortech.2013.08.105.
    1. Nelson TM, Borgogna JL, Brotman RM, Ravel J, Walk ST, Yeoman CJ. Vaginal biogenic amines: biomarkers of bacterial vaginosis or precursors to vaginal dysbiosis? Front Physiol. 2015;6:253. doi: 10.3389/fphys.2015.00253.
    1. Marrazzo JM, Antonio M, Agnew K, Hillier SL. Distribution of genital Lactobacillus strains shared by female sex partners. J Infect Dis. 2009;199(5):680–683. doi: 10.1086/596632.
    1. Antonio MA, Rabe LK, Hillier SL. Colonization of the rectum by Lactobacillus species and decreased risk of bacterial vaginosis. J Infect Dis. 2005;192(3):394–398. doi: 10.1086/430926.
    1. El Aila NA, Tency I, Claeys G, Verstraelen H, Saerens B, Santiago GL, et al. Identification and genotyping of bacteria from paired vaginal and rectal samples from pregnant women indicates similarity between vaginal and rectal microflora. BMC Infect Dis. 2009;9:167. doi: 10.1186/1471-2334-9-167.
    1. Gajer P, Brotman RM, Bai G, Sakamoto J, Schutte UM, Zhong X, et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med. 2012;4(132):132ra52. doi: 10.1126/scitranslmed.3003605.

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