**1. Introduction**

The human body is inhabited by numerous microorganisms that constitute a kind of microbiome. The importance of microorganisms inhabiting various parts of the human body is not fully understood. Little is known about their impact on human growth, development and health. There is particularly little data on the impact of bacteria and viruses on the development of the placenta in normal and complicated pregnancies, e.g., with fetal growth disorders.

Fetal growth retardation, observed in approximately 3–10% of pregnancies, is one of the problems of perinatology, whose etiology and pathogenesis are not fully understood [1,2]. FGR is most commonly defined as the estimated fetal weight below the 10th percentile for gestational age based on prenatal ultrasound assessment [3]. This condition is associated with a number of short-term and long-term complications that can seriously affect the quality of life [4].

About 40% of FGR cases are idiopathic with no identifiable cause. In the remaining 60% of cases, 1/3 of intrauterine growth retardation is caused by genetic abnormalities and 2/3 is induced by environmental factors [5]. Factors affecting the development of intrauterine growth retardation can be divided into four groups: maternal factors, placental factors, fetal factors and infectious factors [6–8].

So far, cases of FGR have been documented with bacterial infections such as mycoplasma, listeria and mycobacteria, tuberculosis, and infection with a virulent, pathogenic *E. coli* strain. There are also indications that the composition of the vaginal flora may increase the likelihood of FGR. Studies have shown that the simultaneous presence of *Bacteroides*, *Prevotella*, *Porphyromonas* spp., *M. hominis*, *U. urealyticum* and *T. vaginalis* doubles the likelihood of FGR [9]. The presence of bacterial and viral infections causes overproduction of pro-inflammatory cytokines in the mother's body, such as interferon, tumor necrosis factor (TNF) or interleukins [10]. This causes widespread inflammation and necrosis, which in the case of the placenta can lead to abnormal distribution of nutrients and oxygen.

The state of the microenvironment of the maternal-fetal unit and its impact on the course of pregnancy, delivery and further health of the child and adult has been controversial for many years. They resulted from technical difficulties related to sampling and their analysis (biomass samples with a low content of microorganisms could be dominated by contamination during sampling or DNA isolation). On the other hand, in the studies carried out so far, we observe a very high methodological heterogeneity of the methods used to detect bacteria and viruses in placental tissues. This applies, for example, to the selection of a sequencing platform, DNA isolation kits and the selection of variable regions of the 16sRNA gene, which affects the ambiguity of the analyzed results. The introduction of new generation sequencing (NGS), mass spectrophotometry, proteomics and bioinformatics analysis of the obtained results enabled new diagnostic possibilities, primarily high sensitivity of biomass diagnostics of the tested material, e.g., bearing.

The presence of microorganisms in the placenta, amniotic fluid, fetal membranes and umbilical cord blood in studies using next-generation DNA sequencing technology undermines the sterility of the intrauterine environment during pregnancy and at the same time refutes the "sterile uterus" hypothesis, which was considered formulated in the early 20th century. The consequences of the presence of bacteria in the uterus are far-reaching in medicine and basic sciences and shed new light on the antibiotic treatment of pregnant women. It has been shown that the state of the biomass of the uterine environment later affects the development of atopy, asthma, allergies and obesity [11–13].

There are two working definitions of the "microbiome". The first definition given by *Nature* defines the "microbiome" as "*all the genetic material it contains*" (*microbiota—the entire collection of microorganisms in a specific niche, such as the human gut*). This can also be called the metagenomic microbiome [14]. The second definition proposed by Whipps et al. defines "microbiome" as "*a distinctive microbial community occupying a fairly well-defined habitat that has distinct physicochemical properties*" [15]. So, the term doesn't just refer to the microorganisms involved, it also covers their mechanisms of action. Both definitions are linked by emphasizing the functional capacity of the microbiome and the resulting activity [16].

The best-known microbiome is the microbiome of the digestive system, in which, apart from potentially pathogenic organisms, bacteria beneficial to metabolism and human health have been identified [17–19]. The microbiome is also called our "second genome" because it is the genome of the microorganisms that inhabit our bodies.

Since 2007 the human microbiome has been studied by the *Human Microbiome Project* (*HMP*) [20]. These studies made it possible to characterize the normal flora of the female genital organ [21]. The results of HMP and Sirota show a low diversity of genital micropopulations with a predominance of *Lactobacillus bacteria cillus* with a slight predominance of *Provotella*, *Grdnerella* and *Atopobium* [20–22]. These species form a "physiological flora" and by their presence prepare the endometrium from embryo implantation to the ability to carry a fetus to term [23].

It is now believed that the baby's microbiome is influenced by both the mother's microbiome and the immediate external environment. Given the important role of the microbiome, it is crucial to know and understand the mechanisms of colonization of the newborn. It has been suggested that the first colonization of the fetus occurs via the placental microbiome, but there is no clear evidence for this [24,25]. Hemochorial placentas found in humans are characterized by high permeability to lipophilic substances, contain a protein-mediated transport system for glucose and amino acids, exhibit exocytosis and endocytosis, and are permeable to hydrophilic substances through pores that can be used for bacterial migration [24,26].
