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Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction

Fetuses diagnosed with fetal growth restriction (FGR) are at an elevated risk of stillbirth and adulthood morbidity. Gut dysbiosis has emerged as one of the impacts of placental insufficiency, which is the main cause of FGR. This study aimed to characterize the relationships among the intestinal mic...

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Autores principales: Tao, Zixin, Chen, Yun, He, Fang, Tang, Jiawei, Zhan, Limei, Hu, Haoyue, Ding, Ziling, Ruan, Shenghang, Chen, Yutao, Chen, Beier, Wang, Yan, Guo, Xiaoling, Xie, Liwei, Zhong, Mei, Huang, Qitao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10269609/
https://www.ncbi.nlm.nih.gov/pubmed/37199635
http://dx.doi.org/10.1128/spectrum.00076-23
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author Tao, Zixin
Chen, Yun
He, Fang
Tang, Jiawei
Zhan, Limei
Hu, Haoyue
Ding, Ziling
Ruan, Shenghang
Chen, Yutao
Chen, Beier
Wang, Yan
Guo, Xiaoling
Xie, Liwei
Zhong, Mei
Huang, Qitao
author_facet Tao, Zixin
Chen, Yun
He, Fang
Tang, Jiawei
Zhan, Limei
Hu, Haoyue
Ding, Ziling
Ruan, Shenghang
Chen, Yutao
Chen, Beier
Wang, Yan
Guo, Xiaoling
Xie, Liwei
Zhong, Mei
Huang, Qitao
author_sort Tao, Zixin
collection PubMed
description Fetuses diagnosed with fetal growth restriction (FGR) are at an elevated risk of stillbirth and adulthood morbidity. Gut dysbiosis has emerged as one of the impacts of placental insufficiency, which is the main cause of FGR. This study aimed to characterize the relationships among the intestinal microbiome, metabolites, and FGR. Characterization was conducted on the gut microbiome, fecal metabolome, and human phenotypes in a cohort of 35 patients with FGR and 35 normal pregnancies (NP). The serum metabolome was analyzed in 19 patients with FGR and 31 normal pregnant women. Multidimensional data was integrated to reveal the links between data sets. A fecal microbiota transplantation mouse model was used to determine the effects of the intestinal microbiome on fetal growth and placental phenotypes. The diversity and composition of the gut microbiota were altered in patients with FGR. A group of microbial species altered in FGR closely correlated with fetal measurements and maternal clinical variables. Fecal and serum metabolism profiles were distinct in FGR patients compared to those in the NP group. Altered metabolites were identified and associated with clinical phenotypes. Integrated multi-omics analysis revealed the interactions among gut microbiota, metabolites, and clinical measurements. Microbiota from FGR gravida transplanted to mice progestationally induced FGR and placental dysfunction, including impaired spiral artery remodeling and insufficient trophoblast cell invasion. Taken together, the integration of microbiome and metabolite profiles from the human cohort indicates that patients with FGR endure gut dysbiosis and metabolic disorders, which contribute to disease pathogenesis. IMPORTANCE Downstream of the primary cause of fetal growth restriction are placental insufficiency and fetal malnutrition. Gut microbiota and metabolites appear to play an important role in the progression of gestation, while dysbiosis induces maternal and fetal complications. Our study elaborates the significant differences in microbiota profiles and metabolome characteristics between women with FGR and normal pregnancies. This is the first attempt so far that reveals the mechanistic links in multi-omics in FGR, providing a novel insight into host-microbe interaction in placenta-derived diseases.
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spelling pubmed-102696092023-06-16 Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction Tao, Zixin Chen, Yun He, Fang Tang, Jiawei Zhan, Limei Hu, Haoyue Ding, Ziling Ruan, Shenghang Chen, Yutao Chen, Beier Wang, Yan Guo, Xiaoling Xie, Liwei Zhong, Mei Huang, Qitao Microbiol Spectr Research Article Fetuses diagnosed with fetal growth restriction (FGR) are at an elevated risk of stillbirth and adulthood morbidity. Gut dysbiosis has emerged as one of the impacts of placental insufficiency, which is the main cause of FGR. This study aimed to characterize the relationships among the intestinal microbiome, metabolites, and FGR. Characterization was conducted on the gut microbiome, fecal metabolome, and human phenotypes in a cohort of 35 patients with FGR and 35 normal pregnancies (NP). The serum metabolome was analyzed in 19 patients with FGR and 31 normal pregnant women. Multidimensional data was integrated to reveal the links between data sets. A fecal microbiota transplantation mouse model was used to determine the effects of the intestinal microbiome on fetal growth and placental phenotypes. The diversity and composition of the gut microbiota were altered in patients with FGR. A group of microbial species altered in FGR closely correlated with fetal measurements and maternal clinical variables. Fecal and serum metabolism profiles were distinct in FGR patients compared to those in the NP group. Altered metabolites were identified and associated with clinical phenotypes. Integrated multi-omics analysis revealed the interactions among gut microbiota, metabolites, and clinical measurements. Microbiota from FGR gravida transplanted to mice progestationally induced FGR and placental dysfunction, including impaired spiral artery remodeling and insufficient trophoblast cell invasion. Taken together, the integration of microbiome and metabolite profiles from the human cohort indicates that patients with FGR endure gut dysbiosis and metabolic disorders, which contribute to disease pathogenesis. IMPORTANCE Downstream of the primary cause of fetal growth restriction are placental insufficiency and fetal malnutrition. Gut microbiota and metabolites appear to play an important role in the progression of gestation, while dysbiosis induces maternal and fetal complications. Our study elaborates the significant differences in microbiota profiles and metabolome characteristics between women with FGR and normal pregnancies. This is the first attempt so far that reveals the mechanistic links in multi-omics in FGR, providing a novel insight into host-microbe interaction in placenta-derived diseases. American Society for Microbiology 2023-05-18 /pmc/articles/PMC10269609/ /pubmed/37199635 http://dx.doi.org/10.1128/spectrum.00076-23 Text en Copyright © 2023 Tao et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Tao, Zixin
Chen, Yun
He, Fang
Tang, Jiawei
Zhan, Limei
Hu, Haoyue
Ding, Ziling
Ruan, Shenghang
Chen, Yutao
Chen, Beier
Wang, Yan
Guo, Xiaoling
Xie, Liwei
Zhong, Mei
Huang, Qitao
Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction
title Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction
title_full Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction
title_fullStr Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction
title_full_unstemmed Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction
title_short Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction
title_sort alterations in the gut microbiome and metabolisms in pregnancies with fetal growth restriction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10269609/
https://www.ncbi.nlm.nih.gov/pubmed/37199635
http://dx.doi.org/10.1128/spectrum.00076-23
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