Semin Reprod Med 2023; 41(05): 151-159
DOI: 10.1055/s-0043-1777758
Review Article

Culturomics in Unraveling the Upper Female Reproductive Tract Microbiota

Robin Vanstokstraeten
1   Department of Microbiology and Infection Control, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
,
Thomas Demuyser
1   Department of Microbiology and Infection Control, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
2   AIMS Lab, Center for Neurosciences, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Brussels, Belgium
,
Denis Piérard
1   Department of Microbiology and Infection Control, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
,
Ingrid Wybo
1   Department of Microbiology and Infection Control, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
,
Christophe Blockeel
3   Brussels IVF, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
,
Shari Mackens
3   Brussels IVF, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
› Author Affiliations

Abstract

In recent years, the study of the human microbiome has surged, shedding light on potential connections between microbiome composition and various diseases. One specific area of intense interest within this research is the female reproductive tract, as it holds the potential to influence the process of embryo implantation. Advanced sequencing technologies have delivered unprecedented insights into the microbial communities, also known as microbiota, residing in the female reproductive tract. However, their efficacy encounters significant challenges when analyzing low-biomass microbiota, such as those present in the endometrium. These molecular techniques are susceptible to contamination from laboratory reagents and extraction kits, leading to sequencing bias that can significantly alter the perceived taxonomy of a sample. Consequently, investigating the microbiota of the upper female reproductive tract necessitates the exploration of alternative methods. In this context, the current review delves into the application of culturomics in unraveling the upper female reproductive tract microbiota. While culturomics holds value in research, its transition to routine clinical practice appears remote, at least in the foreseeable future.



Publication History

Article published online:
15 December 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Ursell LK, Metcalf JL, Parfrey LW, Knight R. Defining the human microbiome. Nutr Rev 2012; 70 Suppl 1 (Suppl. 01) S38-S44
  • 2 Rowland I, Gibson G, Heinken A. et al. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr 2018; 57 (01) 1-24
  • 3 Berg G, Rybakova D, Fischer D. et al. Microbiome definition re-visited: old concepts and new challenges. Microbiome 2020; 8 (01) 103
  • 4 Chaudhari SN, McCurry MD, Devlin AS. Chains of evidence from correlations to causal molecules in microbiome-linked diseases. Nat Chem Biol 2021; 17 (10) 1046-1056
  • 5 Günther V, Allahqoli L, Watrowski R. et al. Vaginal microbiome in reproductive medicine. Diagnostics (Basel) 2022; 12 (08) 1948
  • 6 Tsonis O, Gkrozou F, Paschopoulos M. Microbiome affecting reproductive outcome in ARTs. J Gynecol Obstet Hum Reprod 2021; 50 (03) 102036
  • 7 Altmäe S, Rienzi L. Endometrial microbiome: new hope, or hype?. Reprod Biomed Online 2021; 42 (06) 1051-1052
  • 8 Chen C, Song X, Wei W. et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun 2017; 8 (01) 875
  • 9 Toson B, Simon C, Moreno I. The endometrial microbiome and its impact on human conception. Int J Mol Sci 2022; 23 (01) 485
  • 10 Strowitzki T, Germeyer A, Popovici R, von Wolff M. The human endometrium as a fertility-determining factor. Hum Reprod Update 2006; 12 (05) 617-630
  • 11 Benner M, Ferwerda G, Joosten I, van der Molen RG. How uterine microbiota might be responsible for a receptive, fertile endometrium. Hum Reprod Update 2018; 24 (04) 393-415
  • 12 Molina NM, Sola-Leyva A, Haahr T. et al. Analysing endometrial microbiome: methodological considerations and recommendations for good practice. Hum Reprod 2021; 36 (04) 859-879
  • 13 Reschini M, Benaglia L, Ceriotti F. et al. Endometrial microbiome: sampling, assessment, and possible impact on embryo implantation. Sci Rep 2022; 12 (01) 8467
  • 14 Kennedy KM, de Goffau MC, Perez-Muñoz ME. et al. Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies. Nature 2023; 613 (7945): 639-649
  • 15 Vanstokstraeten R, Mackens S, Callewaert E. et al. Culturomics to investigate the endometrial microbiome: proof-of-concept. Int J Mol Sci 2022; 23 (20) 12212
  • 16 Brooks JP, Edwards DJ, Harwich Jr MD. et al; Vaginal Microbiome Consortium. The truth about metagenomics: quantifying and counteracting bias in 16S rRNA studies. BMC Microbiol 2015; 15: 66
  • 17 Salter SJ, Cox MJ, Turek EM. et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol 2014; 12: 87
  • 18 Liu Y, Ko EY, Wong KK. et al. Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method. Fertil Steril 2019; 112 (04) 707-717.e1
  • 19 Moreno I, Simon C. Relevance of assessing the uterine microbiota in infertility. Fertil Steril 2018; 110 (03) 337-343
  • 20 Chafee M, Maignien L, Simmons SL. The effects of variable sample biomass on comparative metagenomics. Environ Microbiol 2015; 17 (07) 2239-2253
  • 21 Kim D, Hofstaedter CE, Zhao C. et al. Optimizing methods and dodging pitfalls in microbiome research. Microbiome 2017; 5 (01) 52
  • 22 Lagier JC, Armougom F, Million M. et al. Microbial culturomics: paradigm shift in the human gut microbiome study. Clin Microbiol Infect 2012; 18 (12) 1185-1193
  • 23 Lagier JC, Dubourg G, Million M. et al. Culturing the human microbiota and culturomics. Nat Rev Microbiol 2018; 16: 540-550
  • 24 Lagier JC, Hugon P, Khelaifia S, Fournier PE, La Scola B, Raoult D. The rebirth of culture in microbiology through the example of culturomics to study human gut microbiota. Clin Microbiol Rev 2015; 28 (01) 237-264
  • 25 Diop K, Fall NS, Levasseur A. et al. Characterisation of the vaginal microbiota using culturomics and metagenomics suggests transplantation of gut microbiota Into the vagina during bacterial vaginosis. 10 September 2020, PREPRINT (Version 1). Available at Research Square [https://doi.org/10.21203/rs.3.rs-63079/v1]
  • 26 Diakite A, Dubourg G, Dione N. et al. Optimization and standardization of the culturomics technique for human microbiome exploration. Sci Rep 2020; 10 (01) 9674
  • 27 Binek M, Szynkiewicz Z. Multiplication in liquid medium of Treponema sp. isolated from intestinal contents of swine. Acta Microbiol Pol 1985; 34 (02) 167-175
  • 28 Malheiros JM, Correia BSB, Ceribeli C. et al. Comparative untargeted metabolome analysis of ruminal fluid and feces of Nelore steers (Bos indicus). Sci Rep 2021; 11 (01) 12752
  • 29 Artegoitia VM, Foote AP, Lewis RM, Freetly HC. Rumen fluid metabolomics analysis associated with feed efficiency on crossbred steers. Sci Rep 2017; 7 (01) 2864
  • 30 Naud S, Khelaifia S, Mbogning Fonkou MD, Dione N, Lagier JC, Raoult D. Proof of concept of culturomics use of time of care. Front Cell Infect Microbiol 2020; 10: 524769
  • 31 Schubert S, Kostrzewa M. MALDI-TOF MS in the microbiology laboratory: current trends. Curr Issues Mol Biol 2017; 23: 17-20
  • 32 Tsuchida S, Umemura H, Nakayama T. Current status of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) in clinical diagnostic microbiology. Molecules 2020; 25 (20) 4775
  • 33 Janda JM, Abbott SL. 16S rRNA gene sequencing for bacterial identification in the diagnostic laboratory: pluses, perils, and pitfalls. J Clin Microbiol 2007; 45 (09) 2761-2764
  • 34 Cherkaoui A, Renzi G, Vuilleumier N, Schrenzel J. Copan WASPLab automation significantly reduces incubation times and allows earlier culture readings. Clin Microbiol Infect 2019; 25 (11) 1430.e5-1430.e12
  • 35 Cherkaoui A, Schrenzel J. Total laboratory automation for rapid detection and identification of microorganisms and their antimicrobial resistance profiles. Front Cell Infect Microbiol 2022; 12: 807668
  • 36 Quiblier C, Jetter M, Rominski M. et al. Performance of Copan WASP for routine urine microbiology. J Clin Microbiol 2016; 54 (03) 585-592
  • 37 Cherkaoui A, Riat A, Renzi G, Fischer A, Schrenzel J. Diagnostic test accuracy of an automated device for the MALDI target preparation for microbial identification. Eur J Clin Microbiol Infect Dis 2022
  • 38 Smolnikova V, Keburiya L, Iteimowei M. et al. Influence of endometrial microbiota on reproductive outcomes in IVF programs. Am J Biomed Sci Res 2019; 4: 197-200
  • 39 Vanstokstraeten R, Callewaert E, Blotwijk S. et al. Comparing vaginal and endometrial microbiota using culturomics: proof of concept. Int J Mol Sci 2023; 24 (06) 5947
  • 40 Moreno I, Codoñer FM, Vilella F. et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol 2016; 215 (06) 684-703
  • 41 Cariati F, Carotenuto C, Bagnulo F. et al. Endometrial microbiota profile in in-vitro fertilization (IVF) patients by culturomics-based analysis. Front Endocrinol (Lausanne) 2023; 14: 1204729
  • 42 Huang Y, Sheth RU, Zhao S. et al. High-throughput microbial culturomics using automation and machine learning. Nat Biotechnol 2023; 41 (10) 1424-1433
  • 43 Foschi C, Turello G, Lazzarotto T, Ambretti S. Performance of PhenoMatrix for the detection of Group B Streptococcus from recto-vaginal swabs. Diagn Microbiol Infect Dis 2021; 101 (01) 115427
  • 44 Dauwalder O, Michel A, Eymard C. et al. Use of artificial intelligence for tailored routine urine analyses. Clin Microbiol Infect 2021; 27 (08) 1168.e1-1168.e6
  • 45 Jacobs JP, Lagishetty V, Hauer MC. et al. Multi-omics profiles of the intestinal microbiome in irritable bowel syndrome and its bowel habit subtypes. Microbiome 2023; 11 (01) 5