ReviewNature2023
Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies.
Abstract readReview
In one paragraph
Review in Nature, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
232citing papers in PubMed, 2 pooled it
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
232 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- No difference in microbial diversity between bronchoalveolar lavage and tracheal sampling: a systematic review and meta-analysis.BMJ open respiratory research · 2025Pooled it
- Effects of Infant Formula Supplemented With Prebiotics on the Gut Microbiome, Gut Environment, Growth Parameters, and Safety and Tolerance: A Systematic Review and Meta-Analysis.Nutrition reviews · 2025Pooled it
- Maternal-to-neonatal microbial transmission and impact of prenatal probiotics on neonatal gut development.Journal of translational medicine · 2025Trial
- Nationwide cohort study reveals low bifidobacteria and distinct microbiota composition and function in Swedish newborns.Gut microbes · 2026Observational
- Immune System Development-Pro Tips for Paediatricians.Acta paediatrica (Oslo, Norway : 1992) · 2026Review
- Infant microbiome development: a renewed focus on the second six months and complementary feeding.Pediatric research · 2026Article
- The role of the respiratory microbiome in acute and chronic respiratory diseases.Nature reviews. Microbiology · 2026Review
- Plasticity of the infant immune system during the perinatal period.Nature reviews. Immunology · 2026Review
- Age-related changes in the gut microbiota of a long-lived seabird suggest divergence from mammalian models.Royal Society open science · 2026Article
- Bile Microbiota Profiling in Obese and Non-Obese Patients: A Comparison of Shotgun Metagenomics and 16S rRNA Amplicon Sequencing.Life (Basel, Switzerland) · 2026Article
- A roadmap to create FAIR collections of microbial strains.Nature microbiology · 2026Review
- The diagnostic potential of combined quantitative polymerase chain reaction and next-generation sequencing using the same primers for periprosthetic joint infection.Microbiology spectrum · 2026Article
- PREVENT 1, a nationwide Swedish infant cohort for longitudinal gut microbiome profiling and early-life health outcomes: cohort profile.BMJ open · 2026Observational
- Residual yolk depletion matches the establishment of functional oral-intestinal microbiota in hatchling Siamese crocodiles.iScience · 2026Article
- Elucidating the Impact of Bacterial Composition and Diversity on Skin Homeostasis Using a Human 3D In Vitro Skin Model.Microorganisms · 2026Article
- Maternal and infant gut microbiome.iMeta · 2026Review
- Management of Infected, Non-Responsive Atopic Dermatitis in a Romanian Center.Journal of clinical medicine · 2026Article
- The gastrointestinal microbiome and constituent short-chain fatty acids: a narrative review of an underexplored axis in acute lymphoblastic leukemia.Gut pathogens · 2026Review
- Gestational diabetes mellitus and maternal-infant microbiome axis: mechanistic insights and therapeutic interventions.Journal of translational medicine · 2026Review
- The Maternal Microbiome in Pregnancy: From Physiological Changes to Dysbiosis and Obstetrical Complications-Therapeutic Perspectives.Life (Basel, Switzerland) · 2026Review
172 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
46 authors.
Katherine M Kennedy *Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0003-1240-9703
Marcus C de Goffau *Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-7032-1852
Maria Elisa Perez-MuñozDepartment of Agriculture, Food and Nutrition Sciences, University of Alberta, Edmonton, Alberta, Canada.ORCID http://orcid.org/0000-0003-0618-1503
Marie-Claire ArrietaInternational Microbiome Center, University of Calgary, Calgary, Alberta, Canada.ORCID http://orcid.org/0000-0002-4490-3370
Fredrik BäckhedThe Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Peer BorkStructural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-2627-833X
Thorsten BraunDepartment of Obstetrics and Experimental Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-1989-9920
Frederic D BushmanDepartment of Microbiology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4740-4056
Joel DoreUniversité Paris-Saclay, INRAE, MetaGenoPolis, AgroParisTech, MICALIS, Jouy-en-Josas, France.ORCID http://orcid.org/0000-0002-8756-0718
Willem M de VosHuman Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Ashlee M EarlInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7857-9145
Jonathan A EisenDepartment of Evolution and Ecology, University of California, Davis, Davis, CA, USA.ORCID http://orcid.org/0000-0002-0159-2197
Michal A ElovitzMaternal and Child Health Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-7554-7180
Stephanie C Ganal-VonarburgUniversitätsklinik für Viszerale Chirurgie und Medizin, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.ORCID http://orcid.org/0000-0002-2548-7754
Michael G GänzleDepartment of Agriculture, Food and Nutrition Sciences, University of Alberta, Edmonton, Alberta, Canada.ORCID http://orcid.org/0000-0003-0972-928X
Wendy S GarrettDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5092-0150
Lindsay J HallQuadram Institute Bioscience, Norwich Research Park, Norwich, UK.ORCID http://orcid.org/0000-0001-8938-5709
Mathias W HornefInstitute of Medical Microbiology, RWTH University Hospital, Aachen, Germany.ORCID http://orcid.org/0000-0001-6096-9110
Curtis HuttenhowerDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1110-0096
Liza KonnikovaDepartments of Pediatrics and Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-4804-5497
Sarah LebeerDepartment of Bioscience Engineering, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-9400-6918
Andrew J MacphersonDepartment for Biomedical Research (DBMR), University of Bern, Bern, Switzerland.
Ruth C MasseyAPC Microbiome Ireland, University College Cork, Cork, Ireland.
Alice Carolyn McHardyComputational Biology of Infection Research, Helmholtz Centre for Infection Research, Braunschweig, Germany.ORCID http://orcid.org/0000-0003-2370-3430
Omry KorenAzrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.ORCID http://orcid.org/0000-0002-7738-1337
Trevor D LawleyDepartment of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-4805-621X
Ruth E LeyDepartment of Microbiome Science, Max Planck Institute for Developmental Biology, Tübingen, Germany.ORCID http://orcid.org/0000-0002-9087-1672
Liam O'MahonyAPC Microbiome Ireland, University College Cork, Cork, Ireland.ORCID http://orcid.org/0000-0003-4705-3583
Paul W O'TooleAPC Microbiome Ireland, University College Cork, Cork, Ireland.ORCID http://orcid.org/0000-0001-5377-0824
Eric G PamerDuchossois Family Institute, University of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-6755-9904
Julian ParkhillDepartment of Veterinary Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-7069-5958
Jeroen RaesVIB Center for Microbiology, Leuven, Belgium.
Thomas RatteiCentre for Microbiology and Environmental Systems Science, University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0002-0592-7791
Anne SalonenHuman Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-6960-7447
Eran SegalWeizmann Institute of Science, Rehovot, Israel.ORCID http://orcid.org/0000-0002-6859-1164
Nicola SegataDepartment CIBIO, University of Trento, Trento, Italy.ORCID http://orcid.org/0000-0002-1583-5794
Fergus ShanahanAPC Microbiome Ireland, University College Cork, Cork, Ireland.ORCID http://orcid.org/0000-0003-0467-0936
Deborah M SlobodaDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0002-7410-4756
Gordon C S SmithDepartment of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-2124-0997
Harry SokolGastroenterology Department, AP-HP, Saint Antoine Hospital, Centre de Recherche Saint-Antoine, CRSA, INSERM and Sorbonne Université, Paris, France.ORCID http://orcid.org/0000-0002-2914-1822
Tim D SpectorDepartment of Twin Research, King's College London, London, UK.ORCID http://orcid.org/0000-0002-9795-0365
Michael G SuretteDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0003-0086-4995
Gerald W TannockDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Alan W WalkerGut Health Group, Rowett Institute, University of Aberdeen, Aberdeen, UK.ORCID http://orcid.org/0000-0001-5099-8495
Moran YassourSchool of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Jens WalterAPC Microbiome Ireland, University College Cork, Cork, Ireland. jenswalter@ucc.ie.ORCID http://orcid.org/0000-0003-1754-172X
Funding
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6MViral Genomics: evolution, spread, and host interactionsU19AI110818 · NIAID · BROAD INSTITUTE, INC. · PI NEAFSEY, DANIEL E · 2014 to 2024
$66.5MThe role of host-microbial interactions in altering preterm birth risk among black womenR01NR014784 · NINR · UNIVERSITY OF PENNSYLVANIA · PI ELOVITZ, MICHAL AVIVA · 2013 to 2024
$6.4MThe clinical and molecular epidemiology of colistin-resistant carbapenem-resistant Enterobacteriaceae (CRE) in long-term acute care hospitals (LTACHs)R01AI139240 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI LAUTENBACH, EBBING · 2018 to 2023
$3.7MDeciphering the Role of Vaginal Microbes in Preterm birthR01HD102318 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI ELOVITZ, MICHAL AVIVA · 2020 to 2024
$3.4MUnraveling mechanisms by which cervicovaginal microbiota can promote or prevent cervical remodeling and preterm birthR01HD098867 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI ELOVITZ, MICHAL AVIVA · 2020 to 2024
$2.9MROS responses during Vibrio cholerae infectionR01AI120489 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ZHU, JUN · 2016 to 2020
$2.4M(PQ10) The impact of the gut microbiome on the anti-tumor effects of radiotherapyR01CA219871 · NCI · UNIVERSITY OF PENNSYLVANIA · PI FACCIABENE, ANDREA, KOUMENIS, CONSTANTINOS · 2018 to 2022
$2.4MThe Lung DNA Virome in Health and DiseaseR33HL137063 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D, COLLMAN, RONALD G · 2019 to 2021
$2.3MBiotechnology and Biological Sciences Research Council BBS/E/F/00044409Biotechnology and Biological Sciences Research Council BBS/E/F/000PR10353Biotechnology and Biological Sciences Research Council BBS/E/F/000PR10356Medical Research Council MR/K021133/1NCI NIH HHS R01 CA219871NHLBI NIH HHS R33 HL137063NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI120489NIAID NIH HHS R01 AI139240NIAID NIH HHS U19 AI110818NICHD NIH HHS R01 HD098867NICHD NIH HHS R01 HD102318NINR NIH HHS R01 NR014784Wellcome TrustWellcome Trust 100974/C/13/ZWellcome Trust 220876/Z/20/Z
Abstract
Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.
Indexed as
BiomassDNA ContaminationFetusMicrobiotaAmniotic FluidAnimalsFemaleHumansMammalsPlacentaPregnancyReproducibility of Results
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