Origins of the Human Microbiome

Where does our gut microbiome come from?

Much of the microbiome is heritable, but it's not entirely clear how it gets passed to the infant.

General:

Review, 2023: Microbial transmission, colonisation and succession: from pregnancy to infancy https://gut.bmj.com/content/early/2023/01/30/gutjnl-2022-328970

Review, 2015: On the origin of species: Factors shaping the establishment of infant's gut microbiota: http://onlinelibrary.wiley.com/doi/10.1002/bdrc.21113/full

The organ (placenta) that nourishes the developing embryo does not develop properly in mice that lack the usual gut microbes. The maternal microbiome promotes placental development in mice (Oct 2023) https://www.science.org/doi/10.1126/sciadv.adk1887

Strain inheritance and neonatal gut microbiota development: A meta-analysis (Feb 2021) https://www.sciencedirect.com/science/article/pii/S1438422121000126

Loss of microbial diversity in the mother appears to be cumulative over succeeding generations (2018): https://www.mdedge.com/ccjm/article/189671/infectious-diseases/our-missing-microbes-short-term-antibiotic-courses-have-long

Microbial Species that Initially Colonize the Human Gut at Birth or in Early Childhood Can Stay in Human Body for Lifetime (Jan 2021, n=1004) https://link.springer.com/article/10.1007/s00248-020-01636-0

A team led by UCLA researchers says it has developed a faster and more accurate way to determine where the many bacteria that live in, and on, humans come from. FEAST: fast expectation-maximization for microbial source tracking (Jun 2019) https://archive.fo/9fhcB#selection-799.0-799.1 "we can estimate if taxa in the infant gut originate from the birth canal, or if they are derived from some other external source at a later time point. We found that for over 83% of the sink samples, the top contributing sources were from the same family"

Strain-Level Analysis of Mother-to-Child Bacterial Transmission during the First Few Months of Life (2018): https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(18)30319-6 Varying inheritance, likely driven by functional selection.

Ethnic diversity in infant gut microbiota is apparent before the introduction of complementary diets (May 2020, n-106) https://www.tandfonline.com/doi/full/10.1080/19490976.2020.1756150

Selective maternal seeding and environment shape the human gut microbiome (2018): https://genome.cshlp.org/content/early/2018/03/14/gr.233940.117.abstract "we show strong evidence of selective and persistent transmission of maternal strain populations to the vaginally born infant and their occasional replacement by strains from the environment, including those from family members, in later childhood. Thus, the infant gut is seeded by selected maternal bacteria, which expand to form a stable community, with a rare but stable continuing strain influx over time"

Differences in the fecal microbiota of neonates born at home or in the hospital (2018): https://doi.org/10.1038/s41598-018-33995-7

Strain-specific DNA analysis has shown that at least some of the microbiota can be maintained across hundreds of thousands of host generations (2018): https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-018-0457-9

Mouse Microbiomes Are Mostly Inherited. Transmission modes of the mammalian gut microbiota (Oct 2018). The microbiota of the two mouse lineages remained distinct even after 10 generations. Most microbiota genera transmitted vertically. Those taxa that transmitted horizontally through the shared environment of the animal facility tended to be those that include pathogens. https://www.the-scientist.com/news-opinion/mouse-microbiomes-are-mostly-inherited-64998

Researchers found that differences in the first microorganisms that arrive in the gut after birth, and their order of arrival, have a lasting impact on how gastrointestinal system looks later in life. https://www.upi.com/Health_News/2018/09/18/First-gut-bacteria-may-affect-future-ability-to-fight-chronic-diseases/6661537289989/ Experimental evaluation of the importance of colonization history in early-life gut microbiota assembly https://doi.org/10.7554/eLife.36521

Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition (2018): https://www.nature.com/articles/s41586-018-0395-5 | News article on this study: https://www.nature.com/articles/d41586-018-05861-z

Early‐life exposure to gut microbiota from disease protected mice does not impact disease outcome in type 1 diabetes susceptible NOD mice (2018): https://doi.org/10.1111/imcb.12201

Neonatal gut and respiratory microbiota: coordinated development through time and space (2018): https://doi.org/10.1186/s40168-018-0566-5 "community state types of any one body site was highly predictive of the CSTs at other body sites. Findings suggest that early microbiota is shaped by neonatal innate and adaptive developmental responses"

The dynamics of a family’s gut microbiota reveal variations on a theme (2014) https://microbiomejournal.biomedcentral.com/articles/10.1186/2049-2618-2-25 "Although the children and mother shared essentially the identical diet and environment, the children’s microbiotas were not significantly more similar to their mother than they were to their father"

Fish:

"the dominant taxa residing in the gut do not share their niche habitats with the abundant microbiota in the surrounding environment [...], complex gut microbiota could not be simple reflections of environmental microbiota. We further conclude that microbial changes in ontogenesis can be independent of the effects of dietary shifts " (2018): https://www.frontiersin.org/articles/10.3389/fmicb.2018.00495/full

Diet and other environmental factors shape the bacterial communities of fish gut in an eutrophic lake (2018): https://onlinelibrary.wiley.com/doi/abs/10.1111/jam.14064 "fish harbored specific groups of bacteria that do not completely reflect the microbiota of the environment or prey"

Drosophila:

Researchers at Umeå university in Sweden have published a new study showing that the gut bacteria can carry information of past experiences of an altered environment from parents to offspring. Eggs and sperm are not the only information carriers from one generation to the next. "The gut microbiome participates in transgenerational inheritance of low temperature responses in Drosophila melanogaster (2018)" https://phys.org/news/2018-11-parents-guts-tales-children.html - http://dx.doi.org/10.1002/1873-3468.13278

Body Site Origins:

"The study authors also genetically sequenced the gut microbiomes of 175 mothers in addition to their babies and learned that the vaginally born infants’ guts were not determined by bacteria found in the vaginal canal they encountered during birth" (Sep 2019, 596 babies) https://archive.fo/v6wHA#selection-799.0-799.1. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth.

Contrary to the above study: "The vaginal microbiota showed significant correlation with the composition of the babies’ gut microbiota (p-value = 0.002 with a R2 of 15.8%)" (Oct, 2019, n=45, Brazil) https://link.springer.com/article/10.1007/s11274-019-2737-3 The vaginal microbial communities of healthy expectant Brazilian mothers and its correlation with the newborn’s gut colonization.

Mother-to-Infant Microbial Transmission from Different Body Sites Shapes the Developing Infant Gut Microbiome (2018): https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(18)30317-2 Maternal skin and vaginal strains colonize only transiently, and the infant continues to acquire microbes from distinct maternal sources after birth. Maternal gut strains proved more persistent in the infant gut and ecologically better adapted than those acquired from other sources. The maternal gut microbiome is the source of the majority of transmitted strains.

Does the maternal vaginal microbiota play a role in seeding the microbiota of neonatal gut and nose? (2017) http://www.wageningenacademic.com/doi/10.3920/BM2017.0064 "The sources of a large proportion of infant microbiota could not be identified in maternal microbiota, and the sources of seeding of infant gut and nasal microbiota remain to be elucidated."

Bifidobacteria isolated from vaginal and gut microbiomes are indistinguishable by comparative genomics (2018): http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196290 "results of this study support the hypothesis that the vaginal and gut microbiomes are colonized by a shared community of Bifidobacterium, and further emphasize the potential importance of the maternal vaginal microbiome as a source of infant gut microbiota"

The influence of maternal vaginal flora on the intestinal colonization in newborns and 3-month-old infants (2018): https://doi.org/10.1080/14767058.2017.1319352 "Vaginal flora is a potent factor influencing the development of bacterial flora in the neonatal and infantile gut"

Modeling transfer of vaginal microbiota from mother to infant in early life (Jan 2021, 665 mother–child dyads from the COPSAC cohort) https://elifesciences.org/articles/57051#s3

"maternal gut strains are significantly more likely to persist in the infant gut than other strains" https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00251-2 Infant gut strain persistence is associated with maternal origin, phylogeny, and traits including surface adhesion and iron acquisition (Sep 2021).

Breast milk:

30% of the gut microbiome is seeded from breast milk (July 2017): https://jamanetwork.com/journals/jamapediatrics/article-abstract/2625334

Study of human milk functional activity vs actual breastfeeding (latching). Infants unable to actively suck were fed mother's milk. Feeding directly from the breast can contribute to the preterm infant’s microbiome assembly, in addition to the intrinsic health-promoting effects of milk itself. The milk microbiome composition seemed to change following the infant’s latching to the mother’s breast, shifting toward a more diverse microbial community https://doi.org/10.3389/fmicb.2018.02512. Microbial Community Dynamics in Mother’s Milk and Infant’s Mouth and Gut in Moderately Preterm Infants (2018). Additional supporting studies.

The Origin of Human Milk Bacteria: Is There a Bacterial Entero-Mammary Pathway during Late Pregnancy and Lactation? (2014): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224214/

Lactobacillus strains can be transferred to the breast milk following oral intake by pregnant or breastfeeding women (e.g., Arroyo et al., 2010 https://www.ncbi.nlm.nih.gov/pubmed/20455694; Dotterud et al., 2015 https://www.ncbi.nlm.nih.gov/pubmed/25782657; Jiménez et al., 2008 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519365/).

Shared and Distinct Features of Human Milk and Infant Stool Viromes (2018): https://www.frontiersin.org/articles/10.3389/fmicb.2018.01162/full - "viral communities were mostly distinguishable between milk and infant stool, but each was quite distinct from adult stool, urine, and salivary viromes. There were significant differences in viral families in the infant stool (abundant bacteriophages from the family Siphoviridae) compared to milk (abundant bacteriophages from the family Myoviridae), which may reflect significant differences in the bacterial families identified from both sites. Despite the differences in viral taxonomy, we identified a significant number of shared viruses in the milk and stool from all mother-infant pairs"

"breastfeeding duration in early life and pre-school dietary lifestyle correlated with the composition and functional competences of the gut microbiota in the children at school age (6–9 years of age). Our work highlights the persistent effects of breastfeeding duration and pre-school dietary lifestyle". Impact of early events and lifestyle on the gut microbiota and metabolic phenotypes in young school-age children (2019): https://doi.org/10.1186/s40168-018-0608-z

Delivery Mode:

"we assess the effect of delivery mode on gut microbiota, independent of intrapartum antibiotics, by postponing routine antibiotic administration to mothers. This difference seemed independent of the IV antibiotics administered to the mothers" https://archive.ph/t7EaR Impact of delivery mode-associated gut microbiota dynamics on health in the first year of life (Nov 2019, 120 children) "Perhaps therefore not solely vaginal microbiota seeding but also fecal microbiota seeding during vaginal delivery is instrumental in shaping the newborn’s gut microbial environment"

Vaginal birth did not result in infant mycobiomes that were more similar to the mother’s vaginal mycobiome. Therefore, although vertical transmission of specific fungal isolates from mother to infant has been reported, it is likely that other sources (environment, other caregivers) also contribute to early-life mycobiome establishment (2018): http://msystems.asm.org/content/3/3/e00140-17

Preterm infants have distinct microbiomes not explained by mode of delivery, breastfeeding duration or antibiotic exposure (2018): https://academic.oup.com/ije/advance-article-abstract/doi/10.1093/ije/dyy064/4980972

Viruses:

Acquisition, transmission and strain diversity of human gut-colonizing crAss-like phages (Jan 2020): https://www.nature.com/articles/s41467-019-14103-3

A prokaryotic viral sequence is expressed and conserved in mammalian brain (2017): http://www.pnas.org/content/114/27/7118

Fungi:

Analysis of 1,174 time-series metagenomes from 161 premature infants revealed fungal colonization of 13 infants, primarily in the first two weeks of life. Nearly all 24 NICU samples contained eukaryotes, and the most diverse communities were in NICU sinks. Highlighting the potential of hospital-associated fungi to colonize hospitalized infants (2018): https://www.biorxiv.org/content/early/2018/05/17/324566

Human milk fungi: environmental determinants and inter-kingdom associations with milk bacteria in the CHILD Cohort Study (Jun 2020, n=271) https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-020-01829-0 - detected fungi in 21.4% of samples.

Placental microbiome:

Jan 2021 collection "The prenatal microbiome controversy", with commentary and papers for and against: https://www.biomedcentral.com/collections/prenatal

Well-to-Well Contamination as an Additional Confounder in Microbiome Sequence Analyses. "This finding has profound importance in the field, as many current techniques to “decontaminate” a data set simply rely on an assumption that microbial reads found in blanks are contaminants from “outside,” namely, the reagents or consumables". June 2019. Study. Commentary.

Article: Could baby’s first bacteria take root before birth? The womb was thought to be sterile, but some scientists argue that it’s where the microbiome begins. (2018): https://www.nature.com/articles/d41586-018-00664-8

Microbiome in normal and pathological pregnancies: A literature overview (2018): https://onlinelibrary.wiley.com/doi/abs/10.1111/aji.12993 "We present data suggesting that, contrary to traditional understanding, the placenta is not sterile but has a microbial community. Several factors influence the bacterial profile of these women and may explain, at least in part, some of the discrepant findings between studies. Many factors, including genetics, BMI, ethnicity, diet, the use of antibiotics, and environmental conditions, may influence the bacterial profile of pregnant women and help explain some discrepancies in results."

Commentary: Uterine Microbiota: Residents, Tourists, or Invaders? (2018): https://doi.org/10.3389/fimmu.2018.01874 - includes semen as a transmitter of microbes.

Initial microbial community of the neonatal stomach immediately after birth (2018): https://www.tandfonline.com/doi/full/10.1080/19490976.2018.1520578 "Total microbial content was low in many samples, with a substantial number sharing taxonomic composition with negative controls. qPCR targeting the 16S rRNA gene showed that infants delivered vaginally had a higher microbial load than infants delivered by C-section. Samples from many infants had low microbial load near the edge of the detection limit."

In utero human intestine harbors unique metabolomic features including bacterial metabolites (Oct 2020) https://insight.jci.org/articles/view/138751 [Article].

Review, 2018: Uterine microbiome—low biomass and high expectations https://doi.org/10.1093/biolre/ioy257

Review, Jan 2020: https://www.frontiersin.org/articles/10.3389/fimmu.2019.02823/full#h11 - see conclusion.

For:

Review, 2019: Neonatal microbiome – a brief review https://www.tandfonline.com/doi/abs/10.1080/14767058.2019.1583738

Review, 2018: The Prenatal Microbiome: A New Player for Human Health https://www.mdpi.com/2571-5135/7/4/38/htm

The influence of placenta microbiota of normal term pregnant women on immune regulation during pregnancy (Feb 2024, n=26) https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-024-06353-x

Investigating the origin of the fetal gut and placenta microbiome in twins (Jun 2021) https://www.tandfonline.com/doi/abs/10.1080/14767058.2021.1936487 "We performed gene sequencing using the V4 region of 16S rRNA with rigorous negative controls. We clearly identified a distinct placenta microbiome."

Meconium microbiome and its relation to neonatal growth and head circumference catch-up in preterm infants (Sep 2020, n=63) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238632

The meconium microbiota shares more features with the amniotic fluid microbiota than the maternal fecal and vaginal microbiota (Aug 2020, n=39 maternal-neonate pairs) https://www.tandfonline.com/doi/full/10.1080/19490976.2020.1794266 "results strongly suggested that the meconium microbiota was seeded from multiple maternal body sites, and the amniotic fluid microbiota contributed most to the seeding of the meconium microbiota among the investigated maternal body sites"

Comparison of Meconium Microbiome in Dizygotic and Monozygotic Twins Born by Caesarean Section (CS) (Jun 2020, n=56) https://www.frontiersin.org/articles/10.3389/fmicb.2020.01139/full

Viable bacterial colonization is highly limited in the human intestine in utero (Feb 2020) https://www.nature.com/articles/s41591-020-0761-3

Human fetal lungs harbor a microbiome signature (Jan 2020, n=31) https://www.uab.edu/news/research/item/11041-human-fetal-lungs-harbor-a-microbiome-signature

Fetal exposure to the maternal microbiota in humans and mice (Sept 2019) https://insight.jci.org/articles/view/127806 "Our results demonstrate a dynamic, viable mammalian fetal microbiota during in utero development" also says "Cultivatable bacteria in the fetal intestine were found during mid-gestation but not late gestation" which seems very odd/interesting.

Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age (Aug 2019) https://www.fasebj.org/doi/10.1096/fj.201901436RR - article coverage: https://theconversation.com/the-womb-isnt-sterile-healthy-babies-are-born-with-bacteria-and-fungi-in-their-guts-123123

New evidence supports the presence of microbes in the placenta. Visualization of Microbes by 16S in situ Hybridization in Term and Preterm Placentae without Intraamniotic Infection (May 2019) https://www.sciencedaily.com/releases/2019/06/190618132038.htm

The Not-so-Sterile Womb: Evidence That the Human Fetus Is Exposed to Bacteria Prior to Birth (June 2019) "Our results demonstrate that bacterial DNA and SCFAs are present in utero, and have the potential to influence the developing fetal immune system. The DNA in these samples could have come from bacteria that were already dead in the womb" https://medicalxpress.com/news/2019-06-exposure-influential-bacteria-born-evidence.html

Characterisation of the bacterial microbiome in first‐pass meconium using propidium monoazide (PMA) to exclude non‐viable bacterial DNA (2019): https://doi.org/10.1111/lam.13119 "Our findings suggest that the fetal gut is seeded with intact bacterial cells prior to birth. This is an important finding, as exposure to live bacteria during gestation might have a significant impact on the developing fetus"

Bacterial DNA is present in the fetal intestine and overlaps with that in the placenta in mice (2018). http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197439

Conclusion: The female upper genital tract is not sterile. Distinct microbial community profiles in the fallopian tubes of healthy women suggest that this genital tract site supports an endogenous microbiota. (2018): http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=25059

Microbiome in normal and pathological pregnancies: A literature overview (2018): https://onlinelibrary.wiley.com/doi/abs/10.1111/aji.12993 "We present data suggesting that, contrary to traditional understanding, the placenta is not sterile but has a microbial community. Several factors influence the bacterial profile of these women and may explain, at least in part, some of the discrepant findings between studies. Many factors, including genetics, BMI, ethnicity, diet, the use of antibiotics, and environmental conditions, may influence the bacterial profile of pregnant women and help explain some discrepancies in results."

Seeding of the Fetal Gut Microbiome: Insights Into Origins and Significance (2018): https://onlinelibrary.wiley.com/doi/full/10.1111/jpc.13882_7 "All meconium samples contained detectable levels of bacterial DNA and the immunomodulatory SCFAs acetate and propionate, confirming the hypothesis that the fetal gut is inoculated with bacteria in utero. Seeding of the fetal gut microbiome commences prenatally and may originate from the endometrial microbiome present at time of conception; vaginal contribution appears minimal"

HPV infection and bacterial microbiota in the placenta, uterine cervix and oral mucosa (2018): https://www.nature.com/articles/s41598-018-27980-3#Sec7 - "Our data may be interpreted to corroborate the hypothesis of a distinct microbiota of placenta"

Maternal influence on the fetal microbiome in a population-based study of the first-pass meconium (2018): https://sci-hub.tw/https://www.nature.com/articles/pr201829 "The microbiome of the first-pass meconium was not altered by immediate perinatal factors but was affected by maternal factors during pregnancy implying the in utero transfer of microbes and the development of the gut microbiota niche in fetal life"

Comparison of Meconium DNA Extraction Methods for Use in Microbiome Studies (2018): https://www.frontiersin.org/articles/10.3389/fmicb.2018.00270/full

Streptococcus mutans in Umbilical Cord Blood, Peripheral Blood, and Saliva from Healthy Mothers (2018): https://link.springer.com/article/10.1007/s00284-018-1532-y

Fallopian tube microbiota: evidence beyond DNA (2018): https://doi.org/10.2217/fmb-2018-0118 "In the absence of inflammatory pathology, the fallopian tube harbors a visually observable microbial population, which correlates with cultivation-dependent and -independent data, further refuting the sterility of this anatomical niche"

"The intestinal tract of an unborn is, despite general belief, not sterile, but contains bacteria that have been transferred from the mother." (Review, Oct 2017): http://www.wageningenacademic.com/doi/10.3920/BM2017.0066 - https://sci-hub.cc/http://www.wageningenacademic.com/doi/10.3920/BM2017.0066

Microbial communities in placentas from term normal pregnancy exhibit spatially variable profiles. Yet another study showing a placental microbiome (Sept 2017). https://archive.is/W17tE

Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant women (June 2017): https://www.nature.com/articles/s41598-017-03066-4

These data showed that BCG L-forms have the capacity to pass trans-placental barrier and that maternal BCG vaccination affects the placentobiome (2017): https://www.nature.com/articles/s41598-017-17644-z

A 2014 article on this topic: https://www.newscientist.com/article/dn25603-babys-first-gut-bacteria-may-come-from-mums-mouth/

Bacteria Found in Women’s Upper Reproductive Tracts. A new study identifies microorganisms residing in the human fallopian tubes and uterus, but some researchers are skeptical of the findings. 2017: http://www.the-scientist.com/?articles.view/articleNo/50665/title/Bacteria-Found-in-Women-s-Upper-Reproductive-Tracts/

Microorganisms in the human placenta are associated with altered CpG methylation of immune and inflammation-related genes (2017): http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188664

The same thing was thought about breast milk: https://www.ncbi.nlm.nih.gov/pubmed/22974824

Phage passing the gut barrier when bacteria can't: https://www.theatlantic.com/science/archive/2017/12/we-might-absorb-billions-of-viruses-every-day/547415/

Zika virus crosses into the amniotic fluid: http://www.miamiherald.com/news/health-care/article209671964.html

Against:

We conclude that for this sample set, using the methods described, we could not distinguish between placental samples and contamination introduced during DNA purification. (April 2016): https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0172-3

A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Conclusion: evidence is weak. (April 2017): https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0268-4

Bacterial communities found in placental tissues are associated with severe chorioamnionitis and adverse birth outcomes (2017): http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180167

Amniotic fluid from healthy term pregnancies does not harbor a detectable microbial community (2018): https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-018-0475-7 "bacterial microbiota of amniotic fluid was indistinguishable from contamination controls. Viral reads were sparse in the amniotic fluid, and we found no evidence of a core viral community across samples"

Lack of detection of a human placenta microbiome in samples from preterm and term deliveries (2018): https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-018-0575-4

Variations in placental microbiota appear related to premature birth. Enrichment of clinically relevant organisms in spontaneous preterm delivered placenta and reagent contamination across all clinical groups in a large UK pregnancy cohort (2018): http://aem.asm.org/content/early/2018/04/30/AEM.00483-18 - https://www.sciencedaily.com/releases/2018/05/180518133622.htm "analyses of overall community structure did not reveal convincing evidence for the existence of a reproducible ‘preterm placental microbiome’"

Is amniotic fluid of women with uncomplicated term pregnancies free of bacteria? (2018): https://www.ajog.org/article/S0002-9378(18)30438-1/fulltext

The authors of a new study find no evidence for bacteria in the placenta, but others in the field question their interpretation of the data. Human placenta has no microbiome but can contain potential pathogens (Jul 2019) https://www.the-scientist.com/news-opinion/placental-microbiomes-existence-challenged-66215

Deep microbial analysis of multiple placentas shows no evidence for a placental microbiome (Aug 2019) https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1111/1471-0528.15896

Lack of Evidence for Microbiota in the Placental and Fetal Tissues of Rhesus Macaques (May 2020) https://msphere.asm.org/content/5/3/e00210-20

Evidence for contamination as the origin for bacteria found in human placenta rather than a microbiota (Aug 2020) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237232

Fetal meconium does not have a detectable microbiota before birth (May 2021, n=20) https://archive.ph/SoHUI "no microbial signal distinct from negative controls was detected in fetal meconium by 16S. positive aerobic and anaerobic clinical cultures of fetal meconium were identified as likely skin contaminants"

Presence of distinctive microbiome in the first-pass meconium of newborn infants (Sep 2021, n=44) https://www.nature.com/articles/s41598-021-98951-4 "Our results did not support the existence of the placenta and amniotic fluid microbiota in healthy pregnancies. The first-pass meconium samples, formed in utero, appeared to harbor a microbiome that may be explained by perinatal colonization or intrauterine colonization via bacterial extracellular vesicles"

Comprehensive human amniotic fluid metagenomics supports the sterile womb hypothesis (Apr 2022) https://www.nature.com/articles/s41598-022-10869-7

Jan 2023 perspective: Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies https://www.nature.com/articles/s41586-022-05546-8

Mar 2023, Is there a placental microbiota? A critical review and re-analysis of published placental microbiota datasets https://bmcmicrobiol.biomedcentral.com/articles/10.1186/s12866-023-02764-6

The maternal microbiome in normal pregnancy and at delivery by cesarean section and the early developmental phase of the neonatal microbiome—presentation of a longitudinal pilot study (Aug 2024, n=30) https://link.springer.com/article/10.1007/s40629-024-00303-x "the infant and the placenta are not microbially colonized at the time of birth, and the development of the newborn’s microbiome after birth appears to be influenced mainly by environmental exposure"