Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction
ABSTRACT 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 intes...
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2023-06-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00076-23 |
| _version_ | 1797803475378110464 |
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| author | Zixin Tao Yun Chen Fang He Jiawei Tang Limei Zhan Haoyue Hu Ziling Ding Shenghang Ruan Yutao Chen Beier Chen Yan Wang Xiaoling Guo Liwei Xie Mei Zhong Qitao Huang |
| author_facet | Zixin Tao Yun Chen Fang He Jiawei Tang Limei Zhan Haoyue Hu Ziling Ding Shenghang Ruan Yutao Chen Beier Chen Yan Wang Xiaoling Guo Liwei Xie Mei Zhong Qitao Huang |
| author_sort | Zixin Tao |
| collection | DOAJ |
| description | ABSTRACT 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. |
| first_indexed | 2024-03-13T05:21:29Z |
| format | Article |
| id | doaj.art-90a0adbbe6c74695a4714ad6806285c6 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-13T05:21:29Z |
| publishDate | 2023-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-90a0adbbe6c74695a4714ad6806285c62023-06-15T13:18:31ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-06-0111310.1128/spectrum.00076-23Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth RestrictionZixin Tao0Yun Chen1Fang He2Jiawei Tang3Limei Zhan4Haoyue Hu5Ziling Ding6Shenghang Ruan7Yutao Chen8Beier Chen9Yan Wang10Xiaoling Guo11Liwei Xie12Mei Zhong13Qitao Huang14Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaFoshan Women and Children Hospital Affiliated to Southern Medical University, Foshan, Guangdong, ChinaDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaThe First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaFoshan Women and Children Hospital Affiliated to Southern Medical University, Foshan, Guangdong, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, Guangdong, ChinaDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Obstetrics and Gynecology, The First People’s Hospital of Foshan, Foshan, Guangdong, ChinaABSTRACT 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.https://journals.asm.org/doi/10.1128/spectrum.00076-23fetal growth restrictiongut microbiotametabolismmulti-omicsplacenta |
| spellingShingle | Zixin Tao Yun Chen Fang He Jiawei Tang Limei Zhan Haoyue Hu Ziling Ding Shenghang Ruan Yutao Chen Beier Chen Yan Wang Xiaoling Guo Liwei Xie Mei Zhong Qitao Huang Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction Microbiology Spectrum fetal growth restriction gut microbiota metabolism multi-omics placenta |
| 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 | fetal growth restriction gut microbiota metabolism multi-omics placenta |
| url | https://journals.asm.org/doi/10.1128/spectrum.00076-23 |
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