The dogma of the sterile uterus revisited: does microbial seeding occur during fetal life in humans and animals?

Abstract

The debate about the pioneer colonization of the fetus is still open, being the ‘in utero colonization’ hypothesis versus the ‘sterile womb paradigm’ the two opposing sides. The seed in this field of research sprouted in human medicine in the last decade and became a central topic in other mammals as well. We aimed to review the literature on bacterial colonization of the healthy placenta, amniotic fluid, and meconium as representatives of the fetal environment. What emerges is that confirming the colonization of feto-maternal tissues by viable bacteria is challenging in humans as well as in animals. Contamination represents the major risk in this type of research as it can be related to different parts of the study design. Sampling at natural parturition or post-partum introduces risk for colonization by the vaginal microbiome of the mother or from the environment. Culture does not reveal the presence of unculturable microorganisms, and sequencing does not allow confirming bacterial viability, while also introducing the variability associated with the data analysis. Therefore, on the basis of present review, we provide some guidelines on the best practices when performing this type of studies. What emerges from the current literature in humans and animals is that feto-maternal tissues are characterized by a very low biomass, that the viability of bacteria eventually present is still to be confirmed, while massive colonization happens at birth, priming the individual, regardless of species.

Association of Mycoplasma canis with Fertility Disorders in Dogs: A Case Study Supported by Clinical Examination, PCR, 16S Microbiota Profiling, and Serology

“…This method provides information on the overall composition of the bacterial community present in a sample and indicates potential (new) pathogens. This method is complex and involves many steps that can influence the results such as sample collection and storage, DNA extraction and amplification, sequencing, and analyses of obtained results, especially in low-biomass samples [46]. However, species-specific identification based on sequencing of the V4 region of the 16S rRNA gene is difficult and does not provide definitive confirmation that a particular pathogen species is also the cause of a disorder or disease.…”

Establishment of the uterine microbiome following artificial insemination in virgin heifers

“…In the postpartum dairy cow, for example, uterine infection (metritis) can have profound negative effects on reproductive efficiency, animal health, and reduce productivity after calving (Galvão et al, 2019 ; Owens et al, 2020 ; Moraes et al, 2021 ). A sterile uterus was previously thought to be a prerequisite for a healthy uterus and the establishment of pregnancy (Banchi et al, 2024 ). There was also the strongly held belief that the cervix created a barrier that prevented the vaginal microbiome from entering the uterus (Dong et al, 2023 ).…”