Impacts of maternal microbiota and microbial metabolites on fetal intestine, brain, and placenta.

Autor: Husso A; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland., Pessa-Morikawa T; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland., Koistinen VM; Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland.; Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland.; Afekta Technologies Ltd., Kuopio, Finland., Kärkkäinen O; Afekta Technologies Ltd., Kuopio, Finland.; School of Pharmacy, University of Eastern Finland, Kuopio, Finland., Kwon HN; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.; School of Biological Sciences and Basic-Clinical Convergence Research Institute, University of Ulsan, Ulsan, 44610, South Korea., Lahti L; Department of Computing, University of Turku, Turku, Finland., Iivanainen A; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland., Hanhineva K; Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland.; Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland.; Afekta Technologies Ltd., Kuopio, Finland., Niku M; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland. mikael.niku@helsinki.fi.
Jazyk: angličtina
Zdroj: BMC biology [BMC Biol] 2023 Oct 04; Vol. 21 (1), pp. 207. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1186/s12915-023-01709-9
Abstrakt: Background: The maternal microbiota modulates fetal development, but the mechanisms of these earliest host-microbe interactions are unclear. To investigate the developmental impacts of maternal microbial metabolites, we compared full-term fetuses from germ-free and specific pathogen-free mouse dams by gene expression profiling and non-targeted metabolomics.
Results: In the fetal intestine, critical genes mediating host-microbe interactions, innate immunity, and epithelial barrier were differentially expressed. Interferon and inflammatory signaling genes were downregulated in the intestines and brains of the fetuses from germ-free dams. The expression of genes related to neural system development and function, translation and RNA metabolism, and regulation of energy metabolism were significantly affected. The gene coding for the insulin-degrading enzyme (Ide) was most significantly downregulated in all tissues. In the placenta, genes coding for prolactin and other essential regulators of pregnancy were downregulated in germ-free dams. These impacts on gene expression were strongly associated with microbially modulated metabolite concentrations in the fetal tissues. Aryl sulfates and other aryl hydrocarbon receptor ligands, the trimethylated compounds TMAO and 5-AVAB, Glu-Trp and other dipeptides, fatty acid derivatives, and the tRNA nucleobase queuine were among the compounds strongly associated with gene expression differences. A sex difference was observed in the fetal responses to maternal microbial status: more genes were differentially regulated in male fetuses than in females.
Conclusions: The maternal microbiota has a major impact on the developing fetus, with male fetuses potentially more susceptible to microbial modulation. The expression of genes important for the immune system, neurophysiology, translation, and energy metabolism are strongly affected by the maternal microbial status already before birth. These impacts are associated with microbially modulated metabolites. We identified several microbial metabolites which have not been previously observed in this context. Many of the potentially important metabolites remain to be identified.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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