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Microbiome and pregnancy complications
Published in Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos, New Technologies and Perinatal Medicine, 2019
Maria Carmen Collado, Omry Koren
In recent years, the presence of a placental microbiome has been a subject of intensive debate. In 1900 Henry Tissier, a French pediatrician, articulated the sterile-womb dogma, which stated that the fetoplacental unit is germ free, and our first encounter with bacteria occurs upon birth (23). This dogma was subsequently challenged, especially in the last decade, due to the implementation of highly sensitive culture-dependent and culture-independent (next-generation sequencing) approaches to identifying bacteria. In 2014, Aagaard et al. described a unique placental microbiome dominated by the phylum Proteobacteria, and most similar in composition to the oral microbiota, suggesting an oral-placenta transmission route (24). Nevertheless, the descriptions of a true placental microbiome by Aagaard and others have been questioned, especially based on the fact that culture-independent techniques identify DNA and not viable bacterial cells (25). Another problem that has been raised is bacterial contamination of the DNA extraction kits, which is problematic when working with low biomass samples (26). Several consortia are currently engaged in large-scale efforts to determine whether the placental microbiome exists and to ascertain the potential biological role.
Antenatal Care—Nutrition and Lifestyle to Improve Conception and Pregnancy Outcomes
Published in James M. Rippe, Lifestyle Medicine, 2019
Targeting maternal inflammation and oxidative stress appears to be the key to prevention of these disorders. Some of these inflammatory responses are being mediated by the intestinal flora, which is selected for based on diet. By eating a plant-based diet, humans select for more favorable bacterial species that actually improve risk factors for a variety of metabolic diseases.100–103 Maternal diet and the maternal microbiome play crucial roles in what happens to the fetus and infant. A recent study revealed that an infant’s first meeting with microbes and its first intestinal colonization happens in the womb. It is now known that there is a placental microbiome consistent with the maternal oral microbial community. The next meeting with microbes is during birth and then with breastfeeding. From the moment the placenta starts supplying the infant with nutrients, the microbiome is being developed, and that microbiome will determine the health status of the infant.104 Another recent study revealed that a high-fat diet in pregnancy and during breastfeeding causes a microbial dysbiosis in the infant. This dysbiosis can only partially be corrected by a low-fat diet after weaning. The authors provide evidence to support the theory that the maternal diet contributes to establishment of the fetal microbiota, which, in turn, affects intestinal maintenance and metabolic health.104 This underscores the importance of maternal periconceptional, prenatal, and postnatal nutrition.
The Role of the Microbiome on Human Health
Published in Aruna Bakhru, Nutrition and Integrative Medicine, 2018
Rodney R. Dietert, Janice M. Dietert
In utero exposure of the fetus to microbes occurs via the placental microbiome (Aagaard et al. 2014). Interactions between the trophoblast layer, the outer layer of the blastocyst, and the microbiome (Mor and Kwon 2015) affect both fetal immune development and immunoregulation in the mother that is needed to maintain the pregnancy to term (Zheng et al. 2015). Management of the pregnancy needs to include management of the mother's microbiome including that of the placenta. Researchers have suggested that the placental microbiome profile is a driver of both pregnancy outcome and the future destiny for the fetus (Cao et al. 2014; Fox and Eichelberger 2015).
The meconium microbiota shares more features with the amniotic fluid microbiota than the maternal fecal and vaginal microbiota
Published in Gut Microbes, 2020
Qiuwen He, Lai-Yu Kwok, Xiaoxia Xi, Zhi Zhong, Teng Ma, Haiyan Xu, Haixia Meng, Fangqing Zhao, Heping Zhang
The accuracy of profiling microbial communities in low microbial biomass samples (e.g., placenta, amniotic fluid, meconium) has been hindered by our ability to distinguish the authentic signals beyond the level of background contamination. The placental microbiome was firstly characterized metagenomically by Aagaard et al. (2014) using whole-genome shotgun sequencing and 454 pyrosequencing technologies.17 The 454 pyrosequencing technology produced sequences of medium read length (~450 bp).28 By analyzing samples collected from multiple human body sites of pregnant and nonpregnant subjects, Aagaard et al. found that the placental microbiome comprised nonpathogenic commensals most akin to the oral microbiome.17 In contrast, de Goffau et al. (2019) failed to identify distinguishable signals between the placental samples and contaminant controls by sequencing relatively short reads covering the V1-V2 hypervariable regions of the 16S rRNA (~260 bp).27 The conflicting inferences could be resulted from the chosen technologies that relied on different sub-regions and read lengths of 16S rRNA genes, resulting in different power of taxonomic resolution. Moreover, the long-read sequencing technology was potentially advantageous in reducing the contamination risk for metagenomic profiling of low microbial biomass samples, and employing thoughtful filtering settings and vigorous contaminant controls might further ‘decontaminate’ the putative contaminant amplicon sequence variants.22
The impact of the gut microbiota on the reproductive and metabolic endocrine system
Published in Gut Microbes, 2021
Xinyu Qi, Chuyu Yun, Yanli Pang, Jie Qiao
Establishment and maintenance of placental integrity and function are critical for fetal growth, development, and survival. Whether the placenta has its own colonized flora remains controversial. A recent report demonstrated that there was no evidence of the presence of bacteria in the large majority of placental samples from both complicated and uncomplicated pregnancies. However, in approximately 5% of pregnant women, there is an important pathogen, S. agalactiae, in the placenta before the onset of labor.115 Another study indicated that the placenta harbors a low-abundance but metabolically rich microbiome, and variations in the placental microbiome are associated with a remote history of antenatal infection, which may have a profound influence on intrauterine infection and preterm birth.103 According to one recent study of new-borns, the genus Escherichia has a high abundance in meconium and is a strong contributor to early-onset sepsis among extremely low-birth-weight neonates, and the placenta is a likely source of Escherichia in the new-born meconium.116 In a recent study, SCFAs in the bloodstream were able to pass from a non-germ-free mother’s gut microbiota across the placenta and into developing embryos. Embryonic insulin regulation was impaired in embryos from germ-free (GF) mothers, and insulin levels were significantly elevated in the adult stage, providing evidence for the crucial contribution of the maternal gut environment to the metabolic programming of offspring.117 Patients with preeclampsia showed reduced bacterial diversity with obvious dysbiosis. In the placenta of both patients and mice with preeclampsia, the total bacteria, Fusobacterium genus, and inflammatory cytokine levels were significantly increased, suggesting that the gut microbiome is symbiotic and contributes to disease pathogenesis.118
The early life education of the immune system: Moms, microbes and (missed) opportunities
Published in Gut Microbes, 2020
The maternal microbiota in the gut and reproductive tract undergoes significant changes during pregnancy that is influenced by a combination of hormonal, metabolic, and immunological factors as well as by maternal diet, supplement intake, and antibiotics use.28 Alterations in the vaginal microbiota have been linked to preterm birth, a major cause of worldwide neonatal morbidity and mortality.29 Activation of maternal immunity leading to preterm birth has been well documented;30 however, an impact on the developing fetal immune system and subsequent long-term health consequences in offspring cannot be ruled out. Maternal gut microbes metabolize dietary components that is passed to the developing fetus across the placenta. The placenta is the highly adapted primary interface between the mother and the developing fetus that facilitates the exchange of nutrients, gases, xenobiotics, and waste products while protecting the fetus from rejection by the maternal immune system. It is also the focus of a controversial and debated topic about the existence of an intra-uterine microbiome in a healthy pregnancy. The long-held premise that the fetus develops in a sterile environment in utero is being challenged.31 Some studies have demonstrated the presence of low abundance commensal bacteria in the healthy placenta,32,33 while others refute this premise of a placental microbiome.34,35 Distinct bacterial profiles were also reported in gestational week 20 fetal intestines, findings that need to be corroborated in other independent cohorts.36 While exposure of the fetus to live bacteria in utero remains to be confirmed, the fetal tissues are likely exposed to numerous microbial metabolites and microbial fragments of maternal origin that are transferred across the placenta from the maternal serum. Gut microbes can induce an IgG antibody response in hosts that protect from systemic infections.37 Importantly, these commensal-specific IgG antibodies can be transferred across the placenta to the offspring where they regulate mucosal CD4+T cell responses to commensal antigens early after birth.38 Maternal IgG antibodies can also facilitate transfer of bacterial compounds themselves across the placenta.39 In a mouse model where bacteria were only present during pregnancy, maternal antibodies enhanced transfer of bacterial compounds, including ligands for the aryl hydrocarbon receptor (AhR), from the mother to the offspring where they primed the developing immune system. Maternal enteric microbes also ferment dietary fibers to the short-chain fatty acid (SCFA) acetate, that suppresses allergic airway disease, a mouse model for human asthma, by enhancing Treg cell numbers and function in adult offspring.40 In the context of a maternal infection, bacterial peptidoglycan, which is a ligand for Toll-like Receptor 2 (TLR2), traversed the placenta to influence fetal neuro-proliferation.41 Passage of other microbial TLR ligands across the placenta that influence fetal immune development remains a formal possibility.