Marilen Benner

CHAPTER 6 168 spread to other body sites. This sampling of luminal bacteria by DCs has been shown for the gut (219). A similar way of harvesting might already take place before pregnancy to prepare the uterus for placentation. If and how microbiota of gut and uterus might interact remains to be established. The study by Jimenez et al. (2008) fits with the “in utero colonization hypothesis”, which in itself is heavily debated. Recently, Perez-Muños and colleagues have pointed out the shortcomings of published data surrounding the theory that newborns acquire first microbial colonization in utero (2). Studies on in utero colonization and microbial colonization of the non- pregnant uterus share the same methodological and technical limitations that have not been addressed sufficiently to allow any conclusions to be drawn about a core uterine microbiome. We wish to point that even though possibly not determining colonization of the pup in utero, as highlighted by the authors, maternal fertility or uterine health might have still have been affected by the microbial status. Importantly, a role in establishing protection against pathogenic invasion can be envisioned, a threat that mice in protected breeding facilities are a lot less exposed to than humans. Therefore, the fact that germ-free mice are fertile does not rule out a possible impact of uterine microbiota on normal physiology of the human endometrium. CONCLUSION Microbiota might be another piece in the complex mechanism contributing to the cogwheels of hormones, immune cells and physiological adaptations that are needed for successful pregnancy. As described in this review, a vast number of possible physiological contributions of the uterine microbiota can be inferred from other body sites. We highlight that the assessment of uterine microbiota still suffers from many limitations. Nevertheless, the available evidence shows that the presence of uterine 16S rRNA is not solely the result of sampling or analysis errors and deserves to be acknowledged. We conclude that the concept of the sterile endometrium, and the uterine compartment in general, is outworn, although the true core uterine microbiome still needs to be assessed. Functional studies are needed to elucidate the physiological importance of the microbiome in fertility. The challenge of studying reproductive immunology and the microbiota involved is that research on all of the different aspects is still in its infancy; microbiome, immunity, endocrinology in pregnancy, and placental and fetal development need to be studied together to obtain a more comprehensive overview. Thus, experts in various fields, such as microbiology and immunology, need to co-operate. Without this, such a basal process as pregnancy, needed for healthy offspring, will continue to be a mystery.