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Review
. 2023 Dec 15:14:1304727.
doi: 10.3389/fendo.2023.1304727. eCollection 2023.

From gut to placenta: understanding how the maternal microbiome models life-long conditions

Jonathan Ruiz-Triviño  1   2 , Daniel Álvarez  1   2 , Ángela P Cadavid J  1   2   3 , Angela M Alvarez  1   4
Affiliations
Review

From gut to placenta: understanding how the maternal microbiome models life-long conditions

Jonathan Ruiz-Triviño et al. Front Endocrinol (Lausanne). .

Abstract

The microbiome -defined as the microbiota (bacteria, archaea, lower and higher eukaryotes), their genomes, and the surrounding environmental conditions- has a well-described range of physiological functions. Thus, an imbalance of the microbiota composition -dysbiosis- has been associated with pregnancy complications or adverse fetal outcomes. Although there is controversy about the existence or absence of a microbiome in the placenta and fetus during healthy pregnancy, it is known that gut microbiota can produce bioactive metabolites that can enter the maternal circulation and may be actively or passively transferred through the placenta. Furthermore, the evidence suggests that such metabolites have some effect on the fetus. Since the microbiome can influence the epigenome, and modifications of the epigenome could be responsible for fetal programming, it can be experimentally supported that the maternal microbiome and its metabolites could be involved in fetal programming. The developmental origin of health and disease (DOHaD) approach looks to understand how exposure to environmental factors during periods of high plasticity in the early stages of life (e.g., gestational period) influences the program for disease risk in the progeny. Therefore, according to the DOHaD approach, the influence of maternal microbiota in disease development must be explored. Here, we described some of the diseases of adulthood that could be related to alterations in the maternal microbiota. In summary, this review aims to highlight the influence of maternal microbiota on both fetal development and postnatal life, suggesting that dysbiosis on this microbiota could be related to adulthood morbidity.

Keywords: dysbiosis; epigenome; fetal development; microbial metabolites; microbiota; pregnancy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Potential pathways by which the maternal microbiota or its by-products could pass the feto-placental barrier and potentially impact fetal development and postnatal life. 1) Substrates of gut microbiome metabolism such as polyphenols and vitamin A are obtained through the diet. 2) In the gut, the maternal microbiome produces short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and participates in the metabolism of polyphenols into other metabolites such as sterols, catechol, and hippuric acid. These molecules, derived from the metabolism of the gut microbiome, are passively and actively transferred to the bloodstream. In murine models, bacteria of the Clostridia class inhibit the Rdh7 enzyme, responsible for the metabolism of vitamin A in its active form, retinoic acid. 3) At the maternal-fetal interface, ATP-binding cassettes on the apical surface of the syncytiotrophoblast are responsible for the bidirectional transport of metabolites produced by the gut microbiome. SCFAs contribute to placental integrity and development, while TMAO is associated with preeclampsia. 4) Evidence from murine models shows that the absence of the maternal microbiome has a deleterious impact on processes such as microglial development through epigenetic mechanisms. Thus, microbiome-specific differentially accessible regions have been identified. For example, mouse embryos with a normal microbiome experience increased accessibility of key loci for microglial function such as Ly86 and Fosb, during development. This process does not occur in embryos from germ-free (GF) mice. Rdh7, Retinol dehydrogenase 7; Fap2, Fibroblast Activation Protein-2; SCFAs, short chain fatty acids; TMAO, Trimethylamine N-oxide; ABC, ATP binding cassette; SLC, Solute Carrier family.
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References

    1. Berg G, Rybakova D, Fischer D, Cernava T, Vergès MCC, Charles T, et al. . Microbiome definition re-visited: old concepts and new challenges. Microbiome. (2020) 8(1):103. doi: 10.1186/s40168-020-00875-0 - DOI - PMC - PubMed
    1. Gomaa EZ. Human gut microbiota/microbiome in health and diseases: a review. Antonie Van Leeuwenhoek. (2020) 113(12):2019–40. doi: 10.1007/s10482-020-01474-7 - DOI - PubMed
    1. Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C, et al. . Microbiota in health and diseases. Signal Transduct Target Ther (2022) 7(1):135. doi: 10.1038/s41392-022-00974-4 - DOI - PMC - PubMed
    1. Perez-Muñoz ME, Arrieta MC, Ramer-Tait AE, Walter J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome. (2017) 5(1):1–19. doi: 10.1186/s40168-017-0268-4 - DOI - PMC - PubMed
    1. Rehbinder EM, Lødrup Carlsen KC, Staff AC, Angell IL, Landrø L, Hilde K, et al. . Is amniotic fluid of women with uncomplicated term pregnancies free of bacteria. Am J Obstet Gynecol. (2018) 219(3):289.e1–289.e12. doi: 10.1016/j.ajog.2018.05.028 - DOI - PubMed

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The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Estrategia de Sostenibilidad Grupo Reproducción, Universidad de Antioquia UdeA, 2021.

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