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.

Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies / Kennedy, Katherine M; de Goffau, Marcus C; Perez-Muñoz, Maria Elisa; Arrieta, Marie-Claire; Bäckhed, Fredrik; Bork, Peer; Braun, Thorsten; Bushman, Frederic D; Dore, Joel; de Vos, Willem M; Earl, Ashlee M; Eisen, Jonathan A; Elovitz, Michal A; Ganal-Vonarburg, Stephanie C; Gänzle, Michael G; Garrett, Wendy S; Hall, Lindsay J; Hornef, Mathias W; Huttenhower, Curtis; Konnikova, Liza; Lebeer, Sarah; Macpherson, Andrew J; Massey, Ruth C; Mchardy, Alice Carolyn; Koren, Omry; Lawley, Trevor D; Ley, Ruth E; O'Mahony, Liam; O'Toole, Paul W; Pamer, Eric G; Parkhill, Julian; Raes, Jeroen; Rattei, Thomas; Salonen, Anne; Segal, Eran; Segata, Nicola; Shanahan, Fergus; Sloboda, Deborah M; Smith, Gordon C S; Sokol, Harry; Spector, Tim D; Surette, Michael G; Tannock, Gerald W; Walker, Alan W; Yassour, Moran; Walter, Jens. - In: NATURE. - ISSN 1476-4687. - 613:7945(2023), pp. 639-649. [10.1038/s41586-022-05546-8]

Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies

Segata, Nicola;
2023-01-01

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.
2023
7945
Kennedy, Katherine M; de Goffau, Marcus C; Perez-Muñoz, Maria Elisa; Arrieta, Marie-Claire; Bäckhed, Fredrik; Bork, Peer; Braun, Thorsten; Bushman, Frederic D; Dore, Joel; de Vos, Willem M; Earl, Ashlee M; Eisen, Jonathan A; Elovitz, Michal A; Ganal-Vonarburg, Stephanie C; Gänzle, Michael G; Garrett, Wendy S; Hall, Lindsay J; Hornef, Mathias W; Huttenhower, Curtis; Konnikova, Liza; Lebeer, Sarah; Macpherson, Andrew J; Massey, Ruth C; Mchardy, Alice Carolyn; Koren, Omry; Lawley, Trevor D; Ley, Ruth E; O'Mahony, Liam; O'Toole, Paul W; Pamer, Eric G; Parkhill, Julian; Raes, Jeroen; Rattei, Thomas; Salonen, Anne; Segal, Eran; Segata, Nicola; Shanahan, Fergus; Sloboda, Deborah M; Smith, Gordon C S; Sokol, Harry; Spector, Tim D; Surette, Michael G; Tannock, Gerald W; Walker, Alan W; Yassour, Moran; Walter, Jens
Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies / Kennedy, Katherine M; de Goffau, Marcus C; Perez-Muñoz, Maria Elisa; Arrieta, Marie-Claire; Bäckhed, Fredrik; Bork, Peer; Braun, Thorsten; Bushman, Frederic D; Dore, Joel; de Vos, Willem M; Earl, Ashlee M; Eisen, Jonathan A; Elovitz, Michal A; Ganal-Vonarburg, Stephanie C; Gänzle, Michael G; Garrett, Wendy S; Hall, Lindsay J; Hornef, Mathias W; Huttenhower, Curtis; Konnikova, Liza; Lebeer, Sarah; Macpherson, Andrew J; Massey, Ruth C; Mchardy, Alice Carolyn; Koren, Omry; Lawley, Trevor D; Ley, Ruth E; O'Mahony, Liam; O'Toole, Paul W; Pamer, Eric G; Parkhill, Julian; Raes, Jeroen; Rattei, Thomas; Salonen, Anne; Segal, Eran; Segata, Nicola; Shanahan, Fergus; Sloboda, Deborah M; Smith, Gordon C S; Sokol, Harry; Spector, Tim D; Surette, Michael G; Tannock, Gerald W; Walker, Alan W; Yassour, Moran; Walter, Jens. - In: NATURE. - ISSN 1476-4687. - 613:7945(2023), pp. 639-649. [10.1038/s41586-022-05546-8]
File in questo prodotto:
File Dimensione Formato  
403419_3_merged_1667990715.pdf

accesso aperto

Tipologia: Pre-print non referato (Non-refereed preprint)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.92 MB
Formato Adobe PDF
1.92 MB Adobe PDF Visualizza/Apri
s41586-022-05546-8.pdf

Solo gestori archivio

Tipologia: Versione editoriale (Publisher’s layout)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.83 MB
Formato Adobe PDF
1.83 MB Adobe PDF   Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/388851
Citazioni
  • ???jsp.display-item.citation.pmc??? 16
  • Scopus 85
  • ???jsp.display-item.citation.isi??? ND
social impact