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Journal of Medical Microbiology logo Journal of Medical Microbiology

Volume 74, Issue 3

Influence of menstrual cycle and oral contraception on taxonomic composition and gas production in the gut microbiome Open Access

Abstract

Oral contraceptives (OCs) are widely used for birth control and offer benefits such as menstrual cycle regulation and reduced menstrual pain. However, they have also been associated with an increased risk of cancer and reduced bone mass density.

While the gut microbiome is known to interact with endocrine factors, the impact of hormonal OCs on its composition and function remains underexplored. Additionally, we explore the relationship of OC use and the microbiome to gas production, which can cause symptoms and be indicative of poor health.

This study investigates the effects of OCs on the diversity and composition of the gut microbiome and its association with breath hydrogen (H) and methane (CH) levels.

We utilized 16S rRNA gene sequencing to analyse faecal samples from 65 women, comparing OC users with non-users at two menstrual cycle time points. Breath tests measured hydrogen and CH production. Data were analysed for microbial diversity, community composition and correlation with gas production.

There were no differences in overall microbial diversity between OC users and non-users in samples collected on day 2 of the menstrual cycle. However, on day 21, we found a significant difference in microbial richness, suggesting a cycle-dependent effect of OCs on gut microbiota species richness but not composition. We found a strong correlation between H and CH concentrations and an interaction between OC use and the menstrual cycle on H and CH production. We also identified several taxa associated with both high levels of H and CH production and OC use.

Our study highlights the intricate relationships among hormonal contraceptives, the gut microbiota and gas production and connects shifts in the microbiome composition to gastrointestinal symptoms (e.g. gas production) that can impact overall health. This underscores the need for further research on the long-term effects of OCs and for the development of precise therapeutic strategies to address potential adverse effects. Our findings offer new perspectives on the microbiome–hormone–gas production nexus, potentially broadening our understanding of the systemic implications of OCs.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): human gut microbiome , breath hydrogen , breath methane , oral contraceptives and sex hormones
Funding
This study was supported by the:
  • California Prune Board (Award G00012885)
    • Principal Award Recipient: HooshmandShirin
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. The Microbiology Society waived the open access fees for this article.
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2025-03-28
2026-04-18

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References

  1. Daniels K, Abma JC. Current contraceptive status among women aged 15–49: united states, 2015–2017.National Center for Health Statistics; 2018 https://www.cdc.gov/nchs/products/databriefs/db327.htm accessed 5 July 2023
  2. Rivera R, Yacobson I, Grimes D. The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices. Am J Obstet Gynecol 1999; 181:1263–1269 [View Article] [PubMed]
     [Google Scholar]
  3. Burkman R, Schlesselman JJ, Zieman M. Safety concerns and health benefits associated with oral contraception. Am J Obstet Gynecol 2004; 190:S5–22 [View Article] [PubMed]
     [Google Scholar]
  4. Almstedt HC, Cook MM, Bramble LF, Dabir DV, LaBrie JW. Oral contraceptive use, bone mineral density, and bone turnover markers over 12 months in college-aged females. J Bone Miner Metab 2020; 38:544–554 [View Article] [PubMed]
     [Google Scholar]
  5. Bachrach LK. Hormonal contraception and bone health in adolescents. Front Endocrinol 2020; 11:603 [View Article] [PubMed]
     [Google Scholar]
  6. Kuwahara A, Matsuda K, Kuwahara Y, Asano S, Inui T et al. Microbiota-gut-brain axis: enteroendocrine cells and the enteric nervous system form an interface between the microbiota and the central nervous system. Biomed Res 2020; 41:199–216 [View Article] [PubMed]
     [Google Scholar]
  7. Hamamah S, Aghazarian A, Nazaryan A, Hajnal A, Covasa M. Role of microbiota-gut-brain axis in regulating dopaminergic signaling. Biomedicines 2022; 10:436 [View Article] [PubMed]
     [Google Scholar]
  8. Chimerel C, Emery E, Summers DK, Keyser U, Gribble FM et al. Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells. Cell Rep 2014; 9:1202–1208 [View Article] [PubMed]
     [Google Scholar]
  9. Kisiela M, Skarka A, Ebert B, Maser E. Hydroxysteroid dehydrogenases (HSDs) in bacteria: a bioinformatic perspective. J Steroid Biochem Mol Biol 2012; 129:31–46 [View Article] [PubMed]
     [Google Scholar]
  10. Sun L-J, Li J-N, Nie Y-Z. Gut hormones in microbiota-gut-brain cross-talk. Chin Med J 2020; 133:826–833 [View Article]
     [Google Scholar]
  11. Zhang J, Sun Z, Jiang S, Bai X, Ma C et al. Probiotic Bifidobacterium lactis v9 regulates the secretion of sex hormones in polycystic ovary syndrome patients through the gut-brain axis. mSystems 2019; 4:e00017–19 [View Article] [PubMed]
     [Google Scholar]
  12. Ahmed E. Microbial endocrinology: interaction of the microbial hormones with the host. BJSTR 2020; 24: [View Article]
     [Google Scholar]
  13. Sisk-Hackworth L, Brown J, Sau L, Levine AA, Ivy Tam LY et al. Hypogonadal (Gnrh1 hpg) mice reveal niche-specific influence of reproductive axis and sex on intestinal microbial communities. Microbiol 2023 [View Article]
     [Google Scholar]
  14. Flores R, Shi J, Fuhrman B, Xu X, Veenstra TD et al. Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study. J Transl Med 2012; 10:253 [View Article] [PubMed]
     [Google Scholar]
  15. Fuhrman BJ, Feigelson HS, Flores R, Gail MH, Xu X et al. Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women. J Clin Endocrinol Metab 2014; 99:4632–4640 [View Article] [PubMed]
     [Google Scholar]
  16. Rizk MG, Thackray VG. Intersection of polycystic ovary syndrome and the gut microbiome. J Endocr Soc 2021; 5:bvaa177 [View Article] [PubMed]
     [Google Scholar]
  17. Torres PJ, Siakowska M, Banaszewska B, Pawelczyk L, Duleba AJ et al. Gut microbial diversity in women with polycystic ovary syndrome correlates with hyperandrogenism. J Clin Endocrinol Metab 2018; 103:1502–1511 [View Article] [PubMed]
     [Google Scholar]
  18. Chen A, Handzel A, Sau L, Cui L, Kelley ST et al. Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice. Endocrinol Diabetes Metab 2024; 7:e443 [View Article] [PubMed]
     [Google Scholar]
  19. Mihajlovic J, Leutner M, Hausmann B, Kohl G, Schwarz J et al. Combined hormonal contraceptives are associated with minor changes in composition and diversity in gut microbiota of healthy women. Environ Microbiol 2021; 23:3037–3047 [View Article] [PubMed]
     [Google Scholar]
  20. Hua X, Cao Y, Morgan DM, Miller K, Chin SM et al. Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome. J Med Microbiol 2022; 71: [View Article] [PubMed]
     [Google Scholar]
  21. Mutuyemungu E, Singh M, Liu S, Rose DJ. Intestinal gas production by the gut microbiota: a review. J Funct Foods 2023; 100:105367 [View Article]
     [Google Scholar]
  22. Smith NW, Shorten PR, Altermann EH, Roy NC, McNabb WC. Hydrogen cross-feeders of the human gastrointestinal tract. Gut Microbes 2019; 10:270–288 [View Article] [PubMed]
     [Google Scholar]
  23. Kumpitsch C, Fischmeister F, Mahnert A, Lackner S, Wilding M et al. Methane emission of humans is explained by dietary habits, host genetics, local formate availability and a uniform archaeome. Microbiology 2020 [View Article]
     [Google Scholar]
  24. Caldarella MP, Serra J, Azpiroz F, Malagelada J-R. Prokinetic effects in patients with intestinal gas retention. Gastroenterology 2002; 122:1748–1755 [View Article] [PubMed]
     [Google Scholar]
  25. DeMasi T, Tsang M, Mueller J, Giltvedt K, Nguyen TN et al. Prunes may blunt adverse effects of oral contraceptives on bone health in young adult women: a randomized clinical trial. Curr Dev Nutr 2024; 8:104417 [View Article] [PubMed]
     [Google Scholar]
  26. Thompson LR, Sanders JG, McDonald D, Amir A, Ladau J et al. A communal catalogue reveals earth’s multiscale microbial diversity. Nature 2017; 551:457–463 [View Article] [PubMed]
     [Google Scholar]
  27. Caporaso JG, Lauber CL, Walters WA, Berg-Lyons D, Huntley J et al. Ultra-high-throughput microbial community analysis on the illumina HiSeq and MiSeq platforms. ISME J 2012; 6:1621–1624 [View Article] [PubMed]
     [Google Scholar]
  28. Fierer N, Hamady M, Lauber CL, Knight R. The influence of sex, handedness, and washing on the diversity of hand surface bacteria. Proc Natl Acad Sci USA 2008; 105:17994–17999 [View Article] [PubMed]
     [Google Scholar]
  29. Amir A, McDonald D, Navas-Molina JA, Kopylova E, Morton JT et al. Deblur rapidly resolves single-nucleotide community sequence patterns. mSystems 2017; 2:00191–16 [View Article] [PubMed]
     [Google Scholar]
  30. Kaehler BD, Bokulich NA, McDonald D, Knight R, Caporaso JG et al. Species abundance information improves sequence taxonomy classification accuracy. Nat Commun 2019; 10:4643 [View Article] [PubMed]
     [Google Scholar]
  31. Ortiz-Velez AN, Kelley ST. Data-driven mathematical approach for removing rare features in zero-inflated datasets. Bioinform 2023 [View Article]
     [Google Scholar]
  32. Calle ML, Pujolassos M, Susin A. coda4microbiome: compositional data analysis for microbiome cross-sectional and longitudinal studies. BMC Bioinform 2023; 24:82 [View Article] [PubMed]
     [Google Scholar]
  33. Fernandes AD, Macklaim JM, Linn TG, Reid G, Gloor GB. ANOVA-like differential expression (ALDEx) analysis for mixed population RNA-Seq. PLoS One 2013; 8:e67019 [View Article] [PubMed]
     [Google Scholar]
  34. Lin H, Peddada SD. Analysis of compositions of microbiomes with bias correction. Nat Commun 2020; 11:3514 [View Article]
     [Google Scholar]
  35. Hornung BVH, Zwittink RD, Kuijper EJ. Issues and current standards of controls in microbiome research. FEMS Microbiol Ecol 2019; 95: [View Article] [PubMed]
     [Google Scholar]
  36. Meng Q, Ma M, Zhang W, Bi Y, Cheng P et al. The gut microbiota during the progression of atherosclerosis in the perimenopausal period shows specific compositional changes and significant correlations with circulating lipid metabolites. Gut Microbes 2021; 13:1–27 [View Article] [PubMed]
     [Google Scholar]
  37. Arroyo P, Ho BS, Sau L, Kelley ST, Thackray VG. Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome. PLoS One 2019; 14:e0223274 [View Article] [PubMed]
     [Google Scholar]
  38. Traore SI, Khelaifia S, Armstrong N, Lagier JC, Raoult D. Isolation and culture of Methanobrevibacter smithii by co-culture with hydrogen-producing bacteria on agar plates. Clin Microbiol Infect 2019; 25:1561 [View Article] [PubMed]
     [Google Scholar]
  39. Neri-Rosario D, Martínez-López YE, Esquivel-Hernández DA, Sánchez-Castañeda JP, Padron-Manrique C et al. Dysbiosis signatures of gut microbiota and the progression of type 2 diabetes: a machine learning approach in a mexican cohort. Front Endocrinol 2023; 14:1170459 [View Article] [PubMed]
     [Google Scholar]
  40. Aranaz P, Ramos-Lopez O, Cuevas-Sierra A, Martinez JA, Milagro FI et al. A predictive regression model of the obesity-related inflammatory status based on gut microbiota composition. Int J Obes 2021; 45:2261–2268 [View Article]
     [Google Scholar]
  41. Ahmad A, Yang W, Chen G, Shafiq M, Javed S et al. Analysis of gut microbiota of obese individuals with type 2 diabetes and healthy individuals. PLoS One 2019; 14:e0226372 [View Article] [PubMed]
     [Google Scholar]
  42. Wong VW-S, Tse C-H, Lam TT-Y, Wong GL-H, Chim AM-L et al. Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis--a longitudinal study. PLoS One 2013; 8:e62885 [View Article] [PubMed]
     [Google Scholar]
  43. Wang J, Yin Y. Clostridium species for fermentative hydrogen production: an overview. Int J Hydrogen Energy 2021; 46:34599–34625 [View Article]
     [Google Scholar]
  44. Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol 2019; 10:277 [View Article] [PubMed]
     [Google Scholar]
  45. Patra D, Banerjee D, Ramprasad P, Roy S, Pal D et al. Recent insights of obesity-induced gut and adipose tissue dysbiosis in type 2 diabetes. Front Mol Biosci 2023; 10:1224982 [View Article] [PubMed]
     [Google Scholar]
  46. Morotomi M, Nagai F, Sakon H, Tanaka R. Paraprevotella clara gen. nov., sp. nov. and Paraprevotella xylaniphila sp. nov., members of the family “Prevotellaceae” isolated from human faeces. Int J Syst Evol Microbiol 2009; 59:1895–1900 [View Article] [PubMed]
     [Google Scholar]
  47. Louis P, Flint HJ. Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol 2017; 19:29–41 [View Article] [PubMed]
     [Google Scholar]
  48. Wang T, van Dijk L, Rijnaarts I, Hermes GDA, de Roos NM et al. Methanogen levels are significantly associated with fecal microbiota composition and alpha diversity in healthy adults and irritable bowel syndrome patients. Microbiol Spectr 2022; 10:e0165322 [View Article] [PubMed]
     [Google Scholar]
  49. Wang Y, Ouyang M, Gao X, Wang S, Fu C et al. Phocea, pseudoflavonifractor and lactobacillus intestinalis: three potential biomarkers of gut microbiota that affect progression and complications of obesity-induced type 2 diabetes mellitus. DMSO 2020; 13:835–850 [View Article] [PubMed]
     [Google Scholar]
  50. Ke S, Mitchell S, MacArthur M, Kane A, Sinclair D et al. Gut microbiota predicts healthy late-life aging in male mice. Nutrients 2021; 13:3290 [View Article] [PubMed]
     [Google Scholar]
  51. Fischbach MA, Sonnenburg JL. Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe 2011; 10:336–347 [View Article] [PubMed]
     [Google Scholar]
  52. Siddiqui R, Makhlouf Z, Alharbi AM, Alfahemi H, Khan NA. The gut microbiome and female health. Biology 2022; 11:1683 [View Article] [PubMed]
     [Google Scholar]
  53. Benoit SL, Maier RJ, Sawers RG, Greening C. Molecular hydrogen metabolism: a widespread trait of pathogenic bacteria and protists. Microbiol Mol Biol Rev 2020; 84:e00092–19 [View Article] [PubMed]
     [Google Scholar]
  54. Abdelbary MMH, Hatting M, Bott A, Dahlhausen A, Keller D et al. The oral-gut axis: salivary and fecal microbiome dysbiosis in patients with inflammatory bowel disease. Front Cell Infect Microbiol 2022; 12:1010853 [View Article] [PubMed]
     [Google Scholar]
  55. Triantafyllou K, Chang C, Pimentel M. Methanogens, methane and gastrointestinal motility. J Neurogastroenterol Motil 2014; 20:31–40 [View Article] [PubMed]
     [Google Scholar]
  56. Hoegenauer C, Hammer HF, Mahnert A, Moissl-Eichinger C. Methanogenic archaea in the human gastrointestinal tract. Nat Rev Gastroenterol Hepatol 2022; 19:805–813 [View Article] [PubMed]
     [Google Scholar]
  57. Thomas CM, Desmond-Le Quéméner E, Gribaldo S, Borrel G. Factors shaping the abundance and diversity of the gut archaeome across the animal kingdom. Nat Commun 2022; 13:3358 [View Article] [PubMed]
     [Google Scholar]
  58. Youngblut ND, Reischer GH, Dauser S, Maisch S, Walzer C et al. Vertebrate host phylogeny influences gut archaeal diversity. Nat Microbiol 2021; 6:1443–1454 [View Article] [PubMed]
     [Google Scholar]
  59. Campbell A, Gdanetz K, Schmidt AW, Schmidt TM. H2 generated by fermentation in the human gut microbiome influences metabolism and competitive fitness of gut butyrate producers. Microbiome 2023; 11:133 [View Article] [PubMed]
     [Google Scholar]
  60. Villanueva-Millan MJ, Leite G, Wang J, Morales W, Parodi G et al. Methanogens and hydrogen sulfide producing bacteria guide distinct gut microbe profiles and irritable bowel syndrome subtypes. Am J Gastroenterol 2022; 117:2055–2066 [View Article] [PubMed]
     [Google Scholar]
  61. Gibson GR, Cummings JH, Macfarlane GT, Allison C, Segal I et al. Alternative pathways for hydrogen disposal during fermentation in the human colon. Gut 1990; 31:679–683 [View Article] [PubMed]
     [Google Scholar]
  62. Payling LM. The Links Between Human Breath Methane, Dietary Fibre Digestion, and the Gut Microbiota Massey University Manawatu; 2022
     [Google Scholar]
  63. Judkins TC, Dennis-Wall JC, Sims SM, Colee J, Langkamp-Henken B. Stool frequency and form and gastrointestinal symptoms differ by day of the menstrual cycle in healthy adult women taking oral contraceptives: a prospective observational study. BMC Womens Health 2020; 20:136 [View Article] [PubMed]
     [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.001987
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Influence of menstrual cycle and oral contraception on taxonomic composition and gas production in the gut microbiome
J. Med. Microbiol. 74, 001987 (2025); https://doi.org/10.1099/jmm.0.001987
/content/journal/jmm/10.1099/jmm.0.001987
/content/journal/jmm/10.1099/jmm.0.001987
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