Humans and their microbiomes have coevolved as a physiologic community composed of distinct body site niches with metabolic and antigenic diversity. The placental microbiome has not been robustly interrogated, despite recent demonstrations of intracellular bacteria with diverse metabolic and immune regulatory functions. A population-based cohort of placental specimens collected under sterile conditions from 320 subjects with extensive clinical data was established for comparative 16S ribosomal DNA-based and whole-genome shotgun (WGS) metagenomic studies. Identified taxa and their gene carriage patterns were compared to other human body site niches, including the oral, skin, airway (nasal), vaginal, and gut microbiomes from nonpregnant controls. We characterized a unique placental microbiome niche, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most akin (Bray-Curtis dissimilarity <0.3) to the human oral microbiome. 16S-based operational taxonomic unit analyses revealed associations of the placental microbiome with a remote history of antenatal infection (permutational multivariate analysis of variance, P = 0.006), such as urinary tract infection in the first trimester, as well as with preterm birth <37 weeks (P = 0.001).

The Placenta Harbors a Unique Microbiome

The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and disease.

The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota

Placental immune response and its tropism for specific viruses and pathogens affect the outcome of the pregnant woman's susceptibility to and severity of certain infectious diseases. The generalization of pregnancy as a condition of immune suppression or increased risk is misleading and prevents the determination of adequate guidelines for treating pregnant women during pandemics. There is a need to evaluate the interaction of each specific pathogen with the fetal/placental unit and its responses to design the adequate prophylaxis or therapy. The complexity of the immunology of pregnancy and the focus, for many years, on the concept of immunology of pregnancy as an organ transplantation have complicated the field and delayed the development of new guidelines with clinical implications that could help to answer these and other relevant questions. Our challenge as scientists and clinicians interested in the field of reproductive immunology is to evaluate many of the 'classical concepts' to define new approaches for a better understanding of the immunology of pregnancy that will benefit mothers and fetuses in different clinical scenarios.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-0897.2010.00836.x

The Immune System in Pregnancy: A Unique Complexity

https://www.cell.com/trends/molecular-medicine/pdf/S1471-4914(14)00216-0.pdf

The infant microbiome development: mom matters

Problem
The role played by microbial invasion of the amniotic cavity (MIAC) in preterm prelabor rupture of membranes (pPROM) is inadequately characterized, in part because of reliance on cultivation-based methods.

/pdf/prevalence-and-diversity-of-microbes-in-the-amniotic-fluid-1yiycyy37f.pdf

Prevalence and Diversity of Microbes in the Amniotic Fluid, the Fetal Inflammatory Response, and Pregnancy Outcome in Women with Preterm Pre-Labor Rupture of Membranes

Intrauterine infection is a recognized cause of preterm birth. The infectious organisms are believed to originate primarily from the vaginal tract and secondarily from other parts of the body. It is plausible that microbes in the oral cavity can be transmitted to the pregnant uterus. However, direct evidence supporting such a transmission is lacking. In this study, amniotic fluids of 34 pregnant women were examined by PCR using 16S and 23S rRNA universally conserved primers. Bacterial DNA was amplified from the only patient with clinical intrauterine infection and histologic necrotizing acute and chronic chorioamnionitis. One strain, Bergeyella sp. clone AF14, was detected and was 99.7% identical to a previously reported uncultivated oral Bergeyella strain, clone AK152, at the 16S rRNA level. The same strain was detected in the subgingival plaque of the patient but not in her vaginal tract. The 16S-23S rRNA sequence of clone AF14 matched exactly with the sequences amplified from the patient's subgingival plaque. These observations suggest that the Bergeyella strain identified in the patient's intrauterine infection originated from the oral cavity. This is the first direct evidence of oral-utero microbial transmission. The patient's periodontal health during pregnancy was unclear. She did not have detectable periodontal disease during postpartum examination. Bergeyella spp. had not been previously associated with preterm birth and were detected in subgingival plaque of women without clinical levels of intrauterine infection. Uncultivated species may be overlooked opportunistic pathogens in preterm birth. This study sheds new light on the implication of oral bacteria in preterm birth.

Transmission of an Uncultivated Bergeyella Strain from the Oral Cavity to Amniotic Fluid in a Case of Preterm Birth

Evaluation of Fetal Renal Function: Unreliability of Fetal Urinary Electrolytes

Percutaneous umbilical blood sampling allows direct access to the fetal circulation We describe our experience with the procedure in the first 100 patients whose fetuses were at risk for hemolytic anemia, chromosomal abnormalities, coagulopathy, or intrauterine infection Hematologic indices, including hemoglobin, hematocrit, red blood cell count, white blood cell count, and platelet count, were analyzed from 50 of the fetuses who were normal at delivery Normal values and gestational age regression curves (from 17 to 37 weeks' gestation) are presented The technique and complications of the procedure are described Percutaneous umbilical blood sampling affords useful information in prenatal diagnosis and entails a low rate of complications

Percutaneous fetal umbilical blood sampling: procedure safety and normal fetal hematologic indices.

Fetal acardia is a rare but severe congenital anomaly. It involves malformations of the head and upper body and an absent or rudimentary nonfunctioning heart. Acardia occurs only in products of monozygotic splitting with an incidence of 1/35,000 deliveries. While the incidence in monozygotic twins is 1 %, the incidence in monozygotic triplets is thought to be three times higher. 1 The four main types of acardia are as follows: (1) Acardius anceps, with the most developed head and thorax; (2) Acardius acephalus, the most common form, with absent head and thorax; (3) Acardius acormus, the most unusual form, with a fetal head attached to the placenta; and (4) Acardius amorphus, a shapeless mass that cannot be recognized as a human form.' The acardiac fetus, however, may not fit any of the above classical types and usually shows other congenital anomalies. 3

https://onlinelibrary.wiley.com/doi/pdf/10.7863/jum.1991.10.6.341

Color-flow and Doppler velocimetry in prenatal diagnosis of acardiac triplet.

Bladder outlet obstruction secondary to ureterocele is well documented. 1 Fetal bladder obstruction due to ureterocele is usually monitored expectantly in utero and then treated in the neonatal period with endoscopic incision of the ureterocele. 2,3 Fetal bladder outlet obstruction due to ureterocele has also been treated with in utero vesicocentesis. 4 In utero surgery has been reported at 19 weeks with fetal cystoscopy (3.5-mm trocar) and laser incision of the ureterocele. 5 In utero incision of a ureterocele has been performed at 28 weeks with a laser inserted under sonographic guidance through a 19-gauge needle. 6 We present a case of fetal bladder outlet obstruction with a ureterocele relieved by in utero vesicocentesis and multiple colander punctures of the ureterocele by a single fetal insertion of a 20-gauge needle.

https://onlinelibrary.wiley.com/doi/pdf/10.7863/jum.2004.23.4.565

Graham G. Ashmead

Papers

Transmission of an Uncultivated Bergeyella Strain from the Oral Cavity to Amniotic Fluid in a Case of Preterm Birth

Evaluation of Fetal Renal Function: Unreliability of Fetal Urinary Electrolytes

Percutaneous fetal umbilical blood sampling: procedure safety and normal fetal hematologic indices.

Color-flow and Doppler velocimetry in prenatal diagnosis of acardiac triplet.

Fetal bladder outlet obstruction due to ureterocele: in utero "colander" therapy.