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Zhu T, Shen D, Cai X, Jin Y, Tu H, Wang S, Pan Q. The causal relationship between gut microbiota and preterm birth: a two-sample Mendelian randomization study. J Matern Fetal Neonatal Med 2025; 38:2432528. [PMID: 39721770 DOI: 10.1080/14767058.2024.2432528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 11/07/2024] [Accepted: 11/14/2024] [Indexed: 12/28/2024]
Abstract
BACKGROUND Preterm birth, a significant global health concern, has been associated with alterations in the gut microbiota. However, the causal nature of this relationship remains uncertain due to the limitations inherent in observational studies. PURPOSE To investigate the potential causal relationship between gut microbiota imbalances and preterm birth. METHODS We conducted a two-sample Mendelian randomization (MR) study using genome-wide association study (GWAS) data from the MiBioGen consortium focusing on microbiota and preterm birth. Single nucleotide polymorphisms (SNPs) associated with the microbiota were selected as instrumental variables. The inverse variance weighting (IVW) method was used to estimate causality. We confirmed pleiotropy and identified and excluded outlier SNPs using MR-PRESSO and MR-Egger regression. Cochran's Q test was applied to assess heterogeneity among SNPs, and a leave-one-out analysis was performed to evaluate the influence of individual SNPs on overall estimates. RESULTS Our findings provide evidence for a causal link between specific components of the gut microbiota and preterm birth, with the identification of relevant metabolites. CONCLUSION This study highlights the causal role of gut microbiota imbalances in preterm birth, offering novel insights into the development of preterm birth and potential targets for prevention strategies.
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Affiliation(s)
- Tao Zhu
- Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Dandan Shen
- Department of Laboratory Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiao Cai
- Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yuanling Jin
- Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Haixia Tu
- Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Shouxing Wang
- Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qianglong Pan
- Department of Clinical Laboratory, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
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Zhang Y, Yang X, Dong C, Zhang M, Guan Q, Chang H, Hang B, Mao JH, Snijders AM, Xia Y. Trace Element Exposure during Pregnancy Has a Persistent Influence on Perinatal Gut Microbiota in Mother-Infant Dyads. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2025; 59:7820-7834. [PMID: 40145873 DOI: 10.1021/acs.est.4c11640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/28/2025]
Abstract
Trace elements have been recognized as the modifiers of the gut microbiota. However, population-based evidence about their effects on maternal gut microbiota dynamics, as well as the intergenerational impacts on neonatal gut microbiota, has been lacking. We examined the longitudinal microbiota data from mother-infant dyads and demonstrated that maternal trace element exposure played a pivotal role in shaping the composition and similarity of the mother-infant gut microbiota. Specifically, serum levels of cobalt (Co), molybdenum (Mo), and rubidium (Rb) were identified to cause further fluctuation in the shift of the maternal gut microbiota. Antibiotic usage shortly before or on the delivery day, as well as maternal zinc (Zn) exposure, affected the gut microbiota similarity within mother-infant dyads. Rb demonstrated an intergenerational effect on meconium Bifidobacterium abundance by altering its abundance in the maternal gut. Notably, this effect was strengthened in the vaginal delivery group without antibiotic usage, while it was attenuated in the c-section delivery group. Our results suggest that maternal trace element exposure has a persistent influence on perinatal gut microbiota, which offers novel insights into promoting mother and infant health.
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Affiliation(s)
- Yuqing Zhang
- Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing 210004, China
| | - Xu Yang
- State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, Nanjing Medical University, Nanjing 211166, China
- Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Chao Dong
- State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, Nanjing Medical University, Nanjing 211166, China
- Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Mingzhi Zhang
- State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, Nanjing Medical University, Nanjing 211166, China
- Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Quanquan Guan
- State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, Nanjing Medical University, Nanjing 211166, China
- Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Hang Chang
- Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Bo Hang
- Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Jian-Hua Mao
- Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Antoine M Snijders
- Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Yankai Xia
- State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, Nanjing Medical University, Nanjing 211166, China
- Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
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3
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Xie Y, Chen Q, Shan D, Pan X, Hu Y. Unraveling the role of the gut microbiome in pregnancy disorders: insights and implications. Front Cell Infect Microbiol 2025; 15:1521754. [PMID: 40125520 PMCID: PMC11925892 DOI: 10.3389/fcimb.2025.1521754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 02/20/2025] [Indexed: 03/25/2025] Open
Abstract
The gut microbiota is the collective term for the microorganisms that reside in the human gut. In recent years, advances in sequencing technology and bioinformatics gradually revealed the role of gut microbiota in human health. Dramatic changes in the gut microbiota occur during pregnancy due to hormonal and dietary changes, and these changes have been associated with certain gestational diseases such as preeclampsia (PE) and gestational diabetes mellitus (GDM). Modulation of gut microbiota has also been proposed as a potential treatment for these gestational diseases. The present article aims to review current reports on the association between gut microbiota and gestational diseases, explore possible mechanisms, and discuss the potential of probiotics in gestational diseases. Uncovering the link between gut microbiota and gestational diseases could lead to a new therapeutic approach.
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Affiliation(s)
- Yupei Xie
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
- Department of Obstetrics and Gynecology, Qingbaijiang Maternal and Child Health Hospital, Chengdu, China
| | - Qian Chen
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
- Department of Obstetrics and Gynecology, Qingbaijiang Maternal and Child Health Hospital, Chengdu, China
| | - Dan Shan
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
- Department of Obstetrics and Gynecology, Qingbaijiang Maternal and Child Health Hospital, Chengdu, China
| | - Xiongfei Pan
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
- West China Second University Hospital, Sichuan University, Shuangliu Institute of Women’s and Children’s Health, Shuangliu Maternal and Child Health Hospital, Chengdu, China
| | - Yayi Hu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
- Department of Obstetrics and Gynecology, Qingbaijiang Maternal and Child Health Hospital, Chengdu, China
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Zhang J, Li L, Zhang M, Fang J, Xu Z, Zheng Y, Lin Z, Pan M. Distinct vaginal microbiome and metabolome profiles in women with preterm delivery following cervical cerclage. Front Cell Infect Microbiol 2025; 15:1444028. [PMID: 40007613 PMCID: PMC11850995 DOI: 10.3389/fcimb.2025.1444028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 01/07/2025] [Indexed: 02/27/2025] Open
Abstract
Preterm birth (PTB) is a major cause of infant morbidity and mortality. The aim of this study was to investigate the effect of vaginal microbiota and metabolites on the outcome of pregnant women. In this study, a total of 127 pregnant women provided written informed consent prior to enrollment in accordance with the approved institutional guidelines, but only 45 pregnancies met the experimental requirements, and then blood and cervical vaginal fluid (CVF) samples were collected before delivery (at the second week after cervical cerclage). Pregnant women with PTB exhibited high white blood cell and neutrophil contents, high neutrophil-to-lymphocyte ratio (NLR), and high systemic inflammation response index (SIRI) in the blood. Vaginal microbiome revealed that the proportion of beneficial bacteria (including Lactobacillus, [Ruminococcus] gnavus group, and Megamonas) significantly decreased in the PTB group, and the proportion of harmful bacteria (including Desulfovibrionaceae, Helicobacter, and Gardnerella) significantly increased, which is strongly related to the biochemical parameters of blood (white blood cells, neutrophils, NLR, and SIRI). In addition, vaginal metabolomics-based liquid chromatography-Orbitrap-tandem mass spectrometry (LC-Orbitrap-MS/MS) found that the alteration in vaginal metabolites in pregnant women with PTB is involved in starch and sucrose metabolism; arginine and praline metabolism; galactose metabolism; purine metabolism; arginine metabolism; tryptophan metabolism and N-glycan biosynthesis; cysteine and methionine metabolism; taurine and hypotaurine metabolism; amino acid metabolism; propanoate metabolism; valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and steroid hormone biosynthesis. These results elaborated that distinct vaginal microbiome and metabolome profiles in women with preterm delivery following cervical cerclage provide valuable information for establishing the prediction models for PTB.
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Affiliation(s)
| | | | | | | | | | | | - Zhi Lin
- Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China
| | - Mian Pan
- Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China
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Enache RM, Roşu OA, Profir M, Pavelescu LA, Creţoiu SM, Gaspar BS. Correlations Between Gut Microbiota Composition, Medical Nutrition Therapy, and Insulin Resistance in Pregnancy-A Narrative Review. Int J Mol Sci 2025; 26:1372. [PMID: 39941139 PMCID: PMC11818759 DOI: 10.3390/ijms26031372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/31/2025] [Accepted: 02/04/2025] [Indexed: 02/16/2025] Open
Abstract
Many physiological changes accompany pregnancy, most of them involving metabolic perturbations. Alterations in microbiota composition occur both before and during pregnancy and have recently been correlated with an important role in the development of metabolic complications, such as insulin resistance and gestational diabetes mellitus (GDM). These changes may be influenced by physiological adaptations to pregnancy itself, as well as by dietary modifications during gestation. Medical nutritional therapy (MNT) applied to pregnant women at risk stands out as one of the most important factors in increasing the microbiota's diversity at both the species and genus levels. In this review, we discuss the physiological changes during pregnancy and their impact on the composition of the intestinal microbiota, which may contribute to GDM. We also discuss findings from previous studies regarding the effectiveness of MNT in reducing insulin resistance. In the future, additional studies should aim to identify specific gut microbial profiles that serve as early indicators of insulin resistance during gestation. Early diagnosis, achievable through stool analysis or metabolite profiling, may facilitate the timely implementation of dietary or pharmaceutical modifications, thereby mitigating the development of insulin resistance and its associated sequelae.
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Affiliation(s)
- Robert-Mihai Enache
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Oana Alexandra Roşu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (O.A.R.); (M.P.); (L.A.P.)
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Monica Profir
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (O.A.R.); (M.P.); (L.A.P.)
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Luciana Alexandra Pavelescu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (O.A.R.); (M.P.); (L.A.P.)
| | - Sanda Maria Creţoiu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (O.A.R.); (M.P.); (L.A.P.)
| | - Bogdan Severus Gaspar
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Surgery Clinic, Bucharest Emergency Clinical Hospital, 014461 Bucharest, Romania
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Dera N, Kosińska-Kaczyńska K, Żeber-Lubecka N, Brawura-Biskupski-Samaha R, Massalska D, Szymusik I, Dera K, Ciebiera M. Impact of Early-Life Microbiota on Immune System Development and Allergic Disorders. Biomedicines 2025; 13:121. [PMID: 39857705 PMCID: PMC11762082 DOI: 10.3390/biomedicines13010121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 12/26/2024] [Accepted: 01/02/2025] [Indexed: 01/27/2025] Open
Abstract
Introduction: The shaping of the human intestinal microbiota starts during the intrauterine period and continues through the subsequent stages of extrauterine life. The microbiota plays a significant role in the predisposition and development of immune diseases, as well as various inflammatory processes. Importantly, the proper colonization of the fetal digestive system is influenced by maternal microbiota, the method of pregnancy completion and the further formation of the microbiota. In the subsequent stages of a child's life, breastfeeding, diet and the use of antibiotics influence the state of eubiosis, which determines proper growth and development from the neonatal period to adulthood. The literature data suggest that there is evidence to confirm that the intestinal microbiota of the infant plays an important role in regulating the immune response associated with the development of allergic diseases. However, the identification of specific bacterial species in relation to specific types of reactions in allergic diseases is the basic problem. Background: The main aim of the review was to demonstrate the influence of the microbiota of the mother, fetus and newborn on the functioning of the immune system in the context of allergies and asthma. Methods: We reviewed and thoroughly analyzed the content of over 1000 articles and abstracts between the beginning of June and the end of August 2024. Over 150 articles were selected for the detailed study. Results: The selection was based on the PubMed National Library of Medicine search engine, using selected keywords: "the impact of intestinal microbiota on the development of immune diseases and asthma", "intestinal microbiota and allergic diseases", "the impact of intrauterine microbiota on the development of asthma", "intrauterine microbiota and immune diseases", "intrauterine microbiota and atopic dermatitis", "intrauterine microbiota and food allergies", "maternal microbiota", "fetal microbiota" and "neonatal microbiota". The above relationships constituted the main criteria for including articles in the analysis. Conclusions: In the present review, we showed a relationship between the proper maternal microbiota and the normal functioning of the fetal and neonatal immune system. The state of eubiosis with an adequate amount and diversity of microbiota is essential in preventing the development of immune and allergic diseases. The way the microbiota is shaped, resulting from the health-promoting behavior of pregnant women, the rational conduct of the medical staff and the proper performance of the diagnostic and therapeutic process, is necessary to maintain the health of the mother and the child. Therefore, an appropriate lifestyle, rational antibiotic therapy as well as the way of completing the pregnancy are indispensable in the prevention of the above conditions. At the same time, considering the intestinal microbiota of the newborn in relation to the genera and phyla of bacteria that have a potentially protective effect, it is worth noting that the use of suitable probiotics and prebiotics seems to contribute to the protective effect.
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Affiliation(s)
- Norbert Dera
- Department of Obstetrics, Perinatology and Neonatology, Center of Postgraduate Medical Education, 01-809 Warsaw, Poland; (N.D.); (K.K.-K.); (R.B.-B.-S.); (I.S.)
- Warsaw Institute of Women’s Health, 00-189 Warsaw, Poland; (D.M.); (M.C.)
| | - Katarzyna Kosińska-Kaczyńska
- Department of Obstetrics, Perinatology and Neonatology, Center of Postgraduate Medical Education, 01-809 Warsaw, Poland; (N.D.); (K.K.-K.); (R.B.-B.-S.); (I.S.)
| | - Natalia Żeber-Lubecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Center of Postgraduate Medical Education, 02-781 Warsaw, Poland;
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Robert Brawura-Biskupski-Samaha
- Department of Obstetrics, Perinatology and Neonatology, Center of Postgraduate Medical Education, 01-809 Warsaw, Poland; (N.D.); (K.K.-K.); (R.B.-B.-S.); (I.S.)
| | - Diana Massalska
- Warsaw Institute of Women’s Health, 00-189 Warsaw, Poland; (D.M.); (M.C.)
- Second Department of Obstetrics and Gynecology, Center of Postgraduate Medical Education, 00-189 Warsaw, Poland
| | - Iwona Szymusik
- Department of Obstetrics, Perinatology and Neonatology, Center of Postgraduate Medical Education, 01-809 Warsaw, Poland; (N.D.); (K.K.-K.); (R.B.-B.-S.); (I.S.)
| | - Kacper Dera
- Pediatric Ward, Department of Pediatrics, Center of Postgraduate Medical Education, Bielański Hospital, 01-809 Warsaw, Poland
| | - Michał Ciebiera
- Warsaw Institute of Women’s Health, 00-189 Warsaw, Poland; (D.M.); (M.C.)
- Second Department of Obstetrics and Gynecology, Center of Postgraduate Medical Education, 00-189 Warsaw, Poland
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Xu Z, Li J, Hong L, Zhang Y, Wang C, Yang H, Zhao L, Qiu P, Du Z, Wang H. Characteristics of the effects of Polygonati Rhizoma on gut microbiota and metabolites in vitro associated with poor dietary habits in pregnant women. PLoS One 2024; 19:e0314335. [PMID: 39637062 PMCID: PMC11620700 DOI: 10.1371/journal.pone.0314335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 11/08/2024] [Indexed: 12/07/2024] Open
Abstract
Poor dietary habits have been associated with dysbiosis and microbial imbalance in pregnant women. Such imbalances can pose health risks during pregnancy. This study aimed to explore the impact of Polygonati Rhizoma on the gut microbiota of pregnant women through In vitro simulated fermentation. Interestingly, significant differences in microbial community richness and structure were found between the control and the treatment with Polygonati Rhizoma. Analysis of composition and variability indicated that the treatment with Polygonati Rhizoma group showed higher levels of Lactobacillus and Bifidobacterium, but lower levels of Parabacteroides and Lachnoclostridium. The study also investigated specific genera differences between groups using the co-occurrence network analysis and their correlations with microbial metabolites by the redundancy analysis (RDA), Mantel-test network heatmap, and heatmap highlighting the relationships among gut microbiota, short-chain fatty acids (SCFAs), and gases in the absence or presence of Polygonati Rhizoma supplementation. Functional predictions from BugBase phenotype prediction indicated changes in potentially pathogenic and aerobic bacteria in Polygonati Rhizoma supplementation. Overall, the findings provide valuable insights into the influence of Polygonati Rhizoma on the gut microbiota in pregnant women associated with poor dietary habits.
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Affiliation(s)
- Zhiwei Xu
- Jinhua Academy, Zhejiang Chinese Medical University, Jinhua, China
- Second Clinical Medical School, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiabin Li
- Department of Pharmacy, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China
| | - Lue Hong
- First Clinical Medical School, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yangli Zhang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Chunyu Wang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Hailong Yang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Lisha Zhao
- Analysis and Testing Center, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Ping Qiu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhi Du
- Department of Pharmacy, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China
| | - Hui Wang
- Jinhua Academy, Zhejiang Chinese Medical University, Jinhua, China
- Second Clinical Medical School, Zhejiang Chinese Medical University, Hangzhou, China
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
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Xiao Y, Li M, Zheng S, Pan X, Peng Y, Ning P, Zhu G, Wan D, Hu D, Yang F, Xu C. Alterations in maternal-fetal gut and amniotic fluid microbiota associated with fetal growth restriction. BMC Pregnancy Childbirth 2024; 24:728. [PMID: 39516719 PMCID: PMC11546114 DOI: 10.1186/s12884-024-06930-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 10/25/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Fetal growth restriction (FGR) is typically characterised as the fetus' inability to reach its inherent growth potential. A growing body of evidence points to the important role of the maternal gut microbiota in FGR development. However, comprehensive research on changes in maternal-fetal gut and intrauterine microbiota related to FGR is lacking. METHODS In this case-control study, we sequenced bacterial 16S rRNA from 35 maternal faecal, 35 meconium, and 31 amniotic fluid samples collected from 19 pregnant women diagnosed with FGR and 16 healthy controls. We identified putative bacterial taxonomic and functional characteristics associated with FGR by comparing these to control samples. RESULTS We identified 34 differential operational taxonomic units (OTUs) in amniotic fluid, seven differential OTUs in maternal faecal matter, and two differential OTUs in meconium. Compared to controls, FGR subjects exhibited enriched bacterial OTUs of the genus Bacteroides in the maternal gut. They also had depleted OTUs of the order Enterobacterales and genus Pseudomonas in the amniotic fluid and genus Stenotrophomonas in the fetal gut. These altered bacterial OTUs showed a significant correlation with neonatal weight and fetal ultrasonographic indexes. Additionally, we identified differential microbial functional pathways related to glycan and lipid metabolism in the maternal gut. We developed diagnostic biomarkers for FGR based on the maternal-fetal gut and amniotic fluid microbiota. CONCLUSIONS This study offers a comprehensive overview of the shifts in microbial composition and functional pathways in the maternal-fetal gut and amniotic fluid microbiota related to FGR, and present novel insights into the development and screening of FGR. However, the assessment of contamination's impact on meconium and amniotic fluid remains inconclusive, necessitating further rigorous experimentation to address this scientific inquiry in future studies.
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Affiliation(s)
- Yuanling Xiao
- Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Meng Li
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital of Southern Medical University, Foshan, China
| | - Shaoping Zheng
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xiuqin Pan
- Department of Obstetrics and Gynecology, The Second People's Hospital of Qingyuan City, Qingyuan, China
| | - Yan Peng
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital of Southern Medical University, Foshan, China
| | - Peipei Ning
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital of Southern Medical University, Foshan, China
| | - Guangyan Zhu
- Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Defeng Wan
- Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Dongmei Hu
- Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
| | - Fang Yang
- Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
| | - Cailing Xu
- Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
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9
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Cheng T, Wen P, Yu R, Zhang F, Li H, Xu X, Zhao D, Liu F, Su W, Zheng Z, Yang H, Yao J, Jin L. Integrative microbiome and metabolome profiles reveal the impacts of periodontitis via oral-gut axis in first-trimester pregnant women. J Transl Med 2024; 22:819. [PMID: 39227984 PMCID: PMC11370083 DOI: 10.1186/s12967-024-05579-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 08/04/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND Periodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials. METHODS We collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women. RESULTS We demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride. CONCLUSIONS The current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing.
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Affiliation(s)
- Tianfan Cheng
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
| | - Ping Wen
- Institute of Maternal and Child Medicine & Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Rong Yu
- Institute of Maternal and Child Medicine & Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Feng Zhang
- Division of Stomatology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Huijun Li
- Division of Stomatology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Xiaoyi Xu
- Institute of Maternal and Child Medicine & Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
- Center for Disease Control and Prevention, Shenzhen, China
| | - Dan Zhao
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
- Department of Implant Dentistry, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
| | - Fang Liu
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Weilan Su
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Zheng Zheng
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Hong Yang
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Jilong Yao
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Lijian Jin
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
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10
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Han X, Wu TQ, Yao R, Liu C, Chen L, Feng X. Gastroesophageal Reflux Disease and Preterm Birth: Univariate and Multivariate Mendelian Randomization. Int J Womens Health 2024; 16:1389-1399. [PMID: 39157004 PMCID: PMC11330254 DOI: 10.2147/ijwh.s467056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 08/03/2024] [Indexed: 08/20/2024] Open
Abstract
Background Observational studies have established a connection between Gastroesophageal reflux disease (GERD) and preterm birth (PTB). Nevertheless, these correlations can be affected by residual confounding or reverse causality, resulting in ambiguity regarding the connection. The objective of this study was to assess the relationship between genetically predicted GERD and PTB. Methods Initially, we performed bidirectional univariate Mendelian randomization (UVMR) analysis utilizing publicly accessible genome-wide association studies (GWAS) data. The primary analytical approach employed to determine the causal impact between GERD and PTB is the inverse variance weighted technique (IVW). Subsequently, we utilized multivariate Mendelian randomization (MVMR) to adjust for potential factors that could influence the results, such as body mass index (BMI), maternal smoking around birth, educational attainment, household income, and Townsend deprivation index (TDI). Furthermore, we performed a sequence of comprehensive sensitivity analyses to assess the reliability of our MR findings. Results The UVMR analysis results showed a significant correlation between GERD and PTB (odds ratio [OR]: 1.810; 95% confidence interval [CI]: 1.344-2.439; P=9.60E-05) in the IVW model, and the Weighted median method (OR=1.591, 95% CI=1.094-2.315, P=0.015) revealed consistent results. The inverse MR findings suggest no causal link between PTB and the incidence of GERD. In addition, the sensitivity analysis did not detect heterogeneity or horizontal pleiotropy, and the "leave-one-out" examination confirmed that the causal estimation is unlikely to be influenced by the single nucleotide polymorphisms (SNPs) effect. The MVMR analysis demonstrated that the causal association between GERD and PTB still existed after considering BMI, maternal smoking around birth, educational attainment, household income, and TDI (OR=1.921, 95% CI=1.401-2.634, P=5.08E-05). Conclusion This study presents evidence indicating that genetically predicted GERD can heighten the risk of PTB. Therefore, it is advisable to perform focused screening for pregnant women with GERD in order to find the initial signs of PTB and promptly apply intervention strategies to extend the duration of pregnancy.
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Affiliation(s)
- Xinyu Han
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China
| | - Tian Qiang Wu
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China
| | - Ruiting Yao
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China
| | - Chang Liu
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China
| | - Lu Chen
- Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China
| | - Xiaoling Feng
- Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China
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11
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Han M, Wang N, Han W, Liu X, Sun T, Xu J. Specific vaginal and gut microbiome and the anti-tumor effect of butyrate in cervical cancer women. Transl Oncol 2024; 44:101902. [PMID: 38507924 PMCID: PMC10965493 DOI: 10.1016/j.tranon.2024.101902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 09/27/2023] [Accepted: 01/31/2024] [Indexed: 03/22/2024] Open
Abstract
OBJECTIVE To investigate the vaginal and gut microbes changes during the carcinogenesis of cervical and the auxiliary diagnostic value. To investigate the effect of microbiome-specific metabolites butyric on cervical cancer cells. METHODS We studied 416 vaginal 16S rRNA sequencing data and 116 gut sequencing data. Reads were processed using VSEARCH. We used Shannon index, Chao1 index, Simpson diversity index, β diversity index, Linear discriminant analysis Effect Size (LEfSe), co-abundance network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore microbiome differences between groups. We constructed random forest models based on genus and verified its discriminant effect. Finally, we used the cell counting kit-8 (CCK-8) method to detect cell proliferation capacity and flow cytometry to detect apoptosis and induction of cell cycle progression. RESULTS Compared to the non-cancerous population, patients with cervical cancer had unique microbial community characteristics in both vaginal and gut ecological niches. Our predictive model based on genus in two ecological regions achieved high accuracy in the diagnosis of cervical cancer (vaginal model AUC=91.58 %; gut model AUC=99.95 %). Butyric inhibited cervical cancer cell proliferation in a concentration-dependent manner and promoted apoptosis of cancer cells. CONCLUSION Significant differences were found in vaginal and gut microbes in patients with cervical cancer compared to the non-cancerous population. The prediction models constructed at the genus level in both ecological sites have good diagnostic value. Microorganisms may be involved in cervical cancer progression in a metabolite-dependent way, and targeting butyric may provide therapeutic options for cervical cancer.
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Affiliation(s)
- Mengzhen Han
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang 110000, China
| | - Na Wang
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang 110000, China
| | - Wenjie Han
- Department of Breast Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang 110000, China
| | - Xiaolin Liu
- Liaoning Microhealth Biotechnology Co., Ltd, Shanlin Road, Dadong District, Shenyang 110000, China
| | - Tao Sun
- Department of Breast Medicine, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital, Shenyang 110000, China
| | - Junnan Xu
- Department of Breast Medicine, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital, Shenyang 110000, China.
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12
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Powell AM, Khan FZA, Ravel J, Elovitz MA. Untangling Associations of Microbiomes of Pregnancy and Preterm Birth. Clin Perinatol 2024; 51:425-439. [PMID: 38705650 PMCID: PMC11070640 DOI: 10.1016/j.clp.2024.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2024]
Abstract
This review illuminates the complex interplay between various maternal microbiomes and their influence on preterm birth (PTB), a driving and persistent contributor to neonatal morbidity and mortality. Here, we examine the dynamics of oral, gastrointestinal (gut), placental, and vaginal microbiomes, dissecting their roles in the pathogenesis of PTB. Importantly, focusing on the vaginal microbiome and PTB, the review highlights (1) a protective role of Lactobacillus species; (2) an increased risk with select anaerobes; and (3) the influence of social health determinants on the composition of vaginal microbial communities.
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Affiliation(s)
- Anna Maya Powell
- Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Phipps 249, Baltimore, MD 21287, USA
| | - Fouzia Zahid Ali Khan
- Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Phipps 249, Baltimore, MD 21287, USA
| | - Jacques Ravel
- Department of Microbiology and Immunology, Institute for Genome Sciences, 670 West Baltimore Street, 3rd Floor, Room 3173, Baltimore, MD 21201, USA
| | - Michal A Elovitz
- Department of Obstetrics and Gynecology, Women's Health Research, Icahn School of Medicine at Mount Sinai, Women's Biomedical Research Institute, 1468 Madison Avenue, New York, NY 10029, USA.
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13
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Yu HR, Yeh YT, Tzeng HT, Dai HY, Lee WC, Wu KLH, Chan JYH, Tain YL, Hsu CN. Carbohydrate-Mediated Pregnancy Gut Microbiota and Neonatal Low Birth Weight. Nutrients 2024; 16:1326. [PMID: 38732572 PMCID: PMC11085476 DOI: 10.3390/nu16091326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 04/19/2024] [Accepted: 04/26/2024] [Indexed: 05/13/2024] Open
Abstract
The effects of gut microbiota on the association between carbohydrate intake during pregnancy and neonatal low birth weight (LBW) were investigated. A prospective cohort study was conducted with 257 singleton-born mother-child pairs in Taiwan, and maternal dietary intake was estimated using a questionnaire, with each macronutrient being classified as low, medium, or high. Maternal fecal samples were collected between 24 and 28 weeks of gestation, and gut microbiota composition and diversity were profiled using 16S rRNA amplicon gene sequencing. Carbohydrates were the major source of total energy (56.61%), followed by fat (27.92%) and protein (15.46%). The rate of infant LBW was 7.8%, which was positively correlated with maternal carbohydrate intake. In the pregnancy gut microbiota, Bacteroides ovatus and Dorea spp. were indirectly and directly negatively associated with fetal growth, respectively; Rosenburia faecis was directly positively associated with neonatal birth weight. Maternal hypertension during pregnancy altered the microbiota features and was associated with poor fetal growth. Microbiota-accessible carbohydrates can modify the composition and function of the pregnancy gut microbiota, thus providing a potential marker to modulate deviations from dietary patterns, particularly in women at risk of hypertension during pregnancy, to prevent neonatal LBW.
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Affiliation(s)
- Hong-Ren Yu
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Yao-Tsung Yeh
- Aging and Disease Prevention Research Center, Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 831, Taiwan
| | - Hong-Tai Tzeng
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Hong-Ying Dai
- Aging and Disease Prevention Research Center, Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 831, Taiwan
| | - Wei-Chia Lee
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Kay L. H. Wu
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Julie Y. H. Chan
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - You-Lin Tain
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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14
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Tian Z, Zhang X, Yao G, Jin J, Zhang T, Sun C, Wang Z, Zhang Q. Intestinal flora and pregnancy complications: Current insights and future prospects. IMETA 2024; 3:e167. [PMID: 38882493 PMCID: PMC11170975 DOI: 10.1002/imt2.167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 11/27/2023] [Accepted: 12/22/2023] [Indexed: 06/18/2024]
Abstract
Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a unique period in a woman's lifespan, pregnancy is characterized by changes in hormones, immunity, and metabolism. The gut microbiota also changes during this period and plays a crucial role in maintaining a healthy pregnancy. Consequently, anomalies in the composition and function of the gut microbiota, namely, gut microbiota dysbiosis, can predispose individuals to various pregnancy complications, posing substantial risks to both maternal and neonatal health. However, there are still many controversies in this field, such as "sterile womb" versus "in utero colonization." Therefore, a thorough understanding of the roles and mechanisms of gut microbiota in pregnancy and its complications is essential to safeguard the health of both mother and child. This review provides a comprehensive overview of the changes in gut microbiota during pregnancy, its abnormalities in common pregnancy complications, and potential etiological implications. It also explores the potential of gut microbiota in diagnosing and treating pregnancy complications and examines the possibility of gut-derived bacteria residing in the uterus/placenta. Our aim is to expand knowledge in maternal and infant health from the gut microbiota perspective, aiding in developing new preventive and therapeutic strategies for pregnancy complications based on intestinal microecology.
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Affiliation(s)
- Zhenyu Tian
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
| | - Xinjie Zhang
- Department of Biology University College London London UK
| | - Guixiang Yao
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
| | - Jiajia Jin
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
| | - Tongxue Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
| | - Chunhua Sun
- Department of Health Management Center, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan China
| | - Zhe Wang
- Department of Geriatrics Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China
| | - Qunye Zhang
- National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
- Cardiovascular Disease Research Center of Shandong First Medical University Central Hospital Affiliated to Shandong First Medical University Jinan China
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15
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Lu X, Shi Z, Jiang L, Zhang S. Maternal gut microbiota in the health of mothers and offspring: from the perspective of immunology. Front Immunol 2024; 15:1362784. [PMID: 38545107 PMCID: PMC10965710 DOI: 10.3389/fimmu.2024.1362784] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 02/28/2024] [Indexed: 04/17/2024] Open
Abstract
Due to the physiological alteration during pregnancy, maternal gut microbiota changes following the metabolic processes. Recent studies have revealed that maternal gut microbiota is closely associated with the immune microenvironment in utero during pregnancy and plays a vital role in specific pregnancy complications, including preeclampsia, gestational diabetes, preterm birth and recurrent miscarriages. Some other evidence has also shown that aberrant maternal gut microbiota increases the risk of various diseases in the offspring, such as allergic and neurodevelopmental disorders, through the immune alignment between mother and fetus and the possible intrauterine microbiota. Probiotics and the high-fiber diet are effective inventions to prevent mothers and fetuses from diseases. In this review, we summarize the role of maternal gut microbiota in the development of pregnancy complications and the health condition of future generations from the perspective of immunology, which may provide new therapeutic strategies for the health management of mothers and offspring.
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Affiliation(s)
- Xiaowen Lu
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, Hangzhou, China
| | - Zhan Shi
- Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, China
| | - Lingling Jiang
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, Hangzhou, China
| | - Songying Zhang
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, Hangzhou, China
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16
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Hadley M, Oppong AY, Coleman J, Powell AM. Structural Racism and Adverse Pregnancy Outcomes Through the Lens of the Maternal Microbiome. Obstet Gynecol 2023; 142:911-919. [PMID: 37678901 PMCID: PMC10510805 DOI: 10.1097/aog.0000000000005345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 04/22/2023] [Accepted: 05/04/2023] [Indexed: 09/09/2023]
Abstract
Microbiome science offers a glimpse into personalized medicine by characterizing health and disease states according to an individual's microbial signatures. Without a critical examination of the use of race as a variable, microbiome studies may be susceptible to the same pitfalls as other areas of science grounded in racist biology. We will examine the use of race as a biological variable in pregnancy-related microbiome research. Emerging data from studies that investigate the intestinal microbiome in pregnancy suggest strong influence of a poor diet on adverse pregnancy outcomes. Differences in the vaginal microbiome implicated in adverse pregnancy outcomes are frequently attributed to race. We review evidence that links systemic racism to pregnancy health outcome differences with a focus on the vaginal and intestinal microbiomes as well as diet. We also review how structural racism ultimately contributes to inequitable access to healthy food and higher risk environmental exposures among pregnant people of lower socioeconomic status and exacerbates common pregnancy comorbidities.
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Affiliation(s)
- Megan Hadley
- Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; and the University of Chicago School of Medicine, Chicago, Illinois
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17
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Cooper K, Clarke M, Clayton JB. Informatics for your Gut: at the Interface of Nutrition, the Microbiome, and Technology. Yearb Med Inform 2023; 32:89-98. [PMID: 37414029 PMCID: PMC10751132 DOI: 10.1055/s-0043-1768723] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/08/2023] Open
Abstract
BACKGROUND A significant portion of individuals in the United States and worldwide experience diseases related to or driven by diet. As research surrounding user-centered design and the microbiome grows, movement of the spectrum of translational science from bench to bedside for improvement of human health through nutrition becomes more accessible. In this literature survey, we examined recent literature examining informatics research at the interface of nutrition and the microbiome. OBJECTIVES The objective of this survey was to synthesize recent literature describing how technology is being applied to understand health at the interface of nutrition and the microbiome focusing on the perspective of the consumer. METHODS A survey of the literature published between January 1, 2021 and October 10, 2022 was performed using the PubMed database and resulting literature was evaluated against inclusion and exclusion criteria. RESULTS A total of 139 papers were retrieved and evaluated against inclusion and exclusion criteria. After evaluation, 45 papers were reviewed in depth revealing four major themes: (1) microbiome and diet, (2) usability,(3) reproducibility and rigor, and (4) precision medicine and precision nutrition. CONCLUSIONS A review of the relationships between current literature on technology, nutrition and the microbiome, and self-management of dietary patterns was performed. Major themes that emerged from this survey revealed exciting new horizons for consumer management of diet and disease, as well as progress towards elucidating the relationship between diet, the microbiome, and health outcomes. The survey revealed continuing interest in the study of diet-related disease and the microbiome and acknowledgement of needs for data re-use, sharing, and unbiased and rigorous measurement of the microbiome. The literature also showed trends toward enhancing the usability of digital interventions to support consumer health and home management, and consensus building around how precision medicine and precision nutrition may be applied in the future to improve human health outcomes and prevent diet-related disease.
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Affiliation(s)
- Kate Cooper
- School of Interdisciplinary Informatics, College of Information Science and Technology, University of Nebraska at Omaha, Omaha, NE, USA
| | - Martina Clarke
- School of Interdisciplinary Informatics, College of Information Science and Technology, University of Nebraska at Omaha, Omaha, NE, USA
| | - Jonathan B. Clayton
- Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
- Department of Food Science and Technology, University of Nebraska—Lincoln, Lincoln, NE, USA
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
- Nebraska Food for Health Center, University of Nebraska—Lincoln, Lincoln, NE, USA
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18
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Abouzaid M, Howidi N, Badran Z, Mohammed G, Mousa NA. The potential role of the gingival crevicular fluid biomarkers in the prediction of pregnancy complications. Front Med (Lausanne) 2023; 10:1168625. [PMID: 37342498 PMCID: PMC10277493 DOI: 10.3389/fmed.2023.1168625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 05/18/2023] [Indexed: 06/23/2023] Open
Abstract
Early and minimally invasive methods are required to predict the risk of multiple adverse pregnancy outcomes. A potential technique with growing interest utilizes the gingival crevicular fluid (GCF), a physiological serum exudate found in the healthy gingival sulcus and in the periodontal pocket in inflammatory conditions. Analysis of biomarkers in the GCF is a minimally invasive method that can be feasible and cost-effective. The potential use of GCF biomarkers along with other clinical indicators in early pregnancy may provide reliable predictors of several adverse pregnancy outcomes, therefore, reducing both maternal and fetal morbidities. Various studies have reported that increased or decreased concentrations of different biomarkers in GCF are associated with a high risk of developing pregnancy complications. In particular, such associations have been commonly demonstrated with gestational diabetes, pre-eclampsia, and pre-term birth. However, limited evidence is available regarding other pregnancy complications such as preterm premature rupture of membranes, recurrent miscarriage, small for gestational age, and hyperemesis gravidarum. In this review, we discuss the reported association between individual GCF biomarkers and common pregnancy complications. Future research is required to provide more solid evidence of the predictive value of those biomarkers in estimating women's risk for each disorder.
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Affiliation(s)
- Maryam Abouzaid
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Nourhan Howidi
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Zahi Badran
- Periodontology Unit, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Ghada Mohammed
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Noha A. Mousa
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
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19
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Yu HR, Tsai CC, Chan JYH, Lee WC, Wu KLH, Tain YL, Hsu TY, Cheng HH, Huang HC, Huang CH, Pan WH, Yeh YT. A Higher Abundance of Actinomyces spp. in the Gut Is Associated with Spontaneous Preterm Birth. Microorganisms 2023; 11:1171. [PMID: 37317145 DOI: 10.3390/microorganisms11051171] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 04/24/2023] [Accepted: 04/26/2023] [Indexed: 06/16/2023] Open
Abstract
Preterm birth is a major challenge in pregnancy worldwide. Prematurity is the leading cause of death in infants and may result in severe complications. Nearly half of preterm births are spontaneous, but do not have recognizable causes. This study investigated whether the maternal gut microbiome and associated functional pathways might play a key role in spontaneous preterm birth (sPTB). Two hundred eleven women carrying singleton pregnancies were enrolled in this mother-child cohort study. Fecal samples were freshly collected at 24-28 weeks of gestation before delivery, and the 16S ribosomal RNA gene was sequenced. Microbial diversity and composition, core microbiome, and associated functional pathways were then statistically analyzed. Demographic characteristics were collected using records from the Medical Birth Registry and questionnaires. The result showed that the gut microbiome of mothers with over-weight (BMI ≥ 24) before pregnancy have lower alpha diversity than those with normal BMI before pregnancy. A higher abundance of Actinomyces spp. was filtered out from the Linear discriminant analysis (LDA) effect size (LEfSe), Spearman correlation, and random forest model, and was inversely correlated with gestational age in sPTB. The multivariate regression model showed that the odds ratio of premature delivery was 3.274 [95% confidence interval (CI): 1.349; p = 0.010] in the group with over-weight before pregnancy with a cutoff Hit% > 0.022 for Actinomyces spp. The enrichment of Actinomyces spp. was negatively correlated with glycan biosynthesis and metabolism in sPTB by prediction from the Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) platform. Maternal gut microbiota showing a lower alpha diversity, increased abundance of Actinomyces spp., and dysregulated glycan metabolism may be associated with sPTB risk.
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Affiliation(s)
- Hong-Ren Yu
- Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Ching-Chang Tsai
- Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - Julie Y H Chan
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - Wei-Chia Lee
- Division of Urology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Kay L H Wu
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - You-Lin Tain
- Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Te-Yao Hsu
- Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - Hsin-Hsin Cheng
- Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - Hsin-Chun Huang
- Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Cheng-Hsieh Huang
- Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung 83130, Taiwan
- Aging and Disease Prevention Research Center, Fooyin University, Kaohsiung 83130, Taiwan
- BioMed Analysis Center, Fooyin University Hospital, Pingtung 92847, Taiwan
- Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 83130, Taiwan
| | - Wen-Harn Pan
- Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
| | - Yao-Tsung Yeh
- Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung 83130, Taiwan
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Yu Y, Groth SW. Risk factors of lower birth weight, small-for-gestational-age infants, and preterm birth in pregnancies following bariatric surgery: a scoping review. Arch Gynecol Obstet 2023; 307:343-378. [PMID: 35332360 DOI: 10.1007/s00404-022-06480-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 02/17/2022] [Indexed: 12/14/2022]
Abstract
PURPOSE Bariatric surgery increases the risk of lower birth weight, small-for-gestational-age (SGA) infants, and preterm birth in a subsequent pregnancy. However, the factors that contribute to these adverse birth outcomes are unclear. This review aimed to collate available information about risk factors of lower birth weight, SGA, and preterm birth following bariatric surgery. METHODS A literature search was conducted using five databases (PubMed, PsycINFO, EMBASE, Web of Science, and Cochrane Library) to obtain relevant studies. RESULTS A total number of 85 studies were included. Studies generally excluded surgery-to-conception interval, pregnancy complications, cigarette use, and maternal age as influencing factors of birth weight, SGA, or preterm birth. In contrast, most studies found that malabsorptive procedures, lower gestational weight gain, lower glucose levels, abdominal pain, and insufficient prenatal care were associated with an elevated risk of adverse birth outcomes. Findings were mixed regarding the effects of surgery-to-conception weight loss, pre-pregnancy body mass index, micronutrient deficiency, and lipid levels on birth outcomes. The examination of maternal microbiome profiles, placental function, alcohol use, and exercise was limited to one study; therefore, no conclusions could be made. CONCLUSION This review identified factors that appear to be associated (e.g., surgery type) or not associated (e.g., surgery-to-conception interval) with birth outcomes following bariatric surgery. The mixed findings and the limited number of studies on several variables (e.g., micronutrients, exercise) highlight the need for further investigation. Additionally, future studies may benefit from exploring interactions among risk factors and expanding to assess additional exposures such as maternal mental health.
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Affiliation(s)
- Yang Yu
- School of Nursing, University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
| | - Susan W Groth
- School of Nursing, University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA
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21
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He X, Li Z, Li X, Zhao H, Hu Y, Han W, Wang C, Yin C, Chen Y. The fecal microbiota of gravidas with fetal growth restriction newborns characterized by metagenomic sequencing. Curr Res Transl Med 2023; 71:103354. [PMID: 36434943 DOI: 10.1016/j.retram.2022.103354] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 03/25/2022] [Accepted: 05/30/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Fetal growth restriction (FGR) is a complex obstetric complication with various causes and of great harm. However, the specific pathogenesis of FGR is unclear, which limits its effective treatment. Gut microbiota dysbiosis was found to be important in pathogenesis of various diseases. However, its role in FGR development remains unclear and needs to be clarified. METHODS In our case-control study, we recruited eight FGR and eight control female participants and collected their fecal samples in third trimester before delivery. We performed metagenomic sequencing and bioinformatic analysis to compare the gut microbiota composition and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the two groups. RESULTS Our results showed that totally 20 gut microbes were significantly different between two groups (p<0•05), and the correlation analysis found that g__Roseomonas and g__unclassified_f__Propionibacteriaceae were significantly positive correlated with both maternal body mass index (BMI) before delivery, placental weight, and neonatal birth weight (BW) percentile (all p<0•05), while g__Marinisporobacter and g__Sphingomonas were significantly negative correlated with both neonatal BMI and neonatal BW percentile (all p<0•05). Through KEGG pathway analysis, we found that the abundance of the Nitrogen metabolism pathway decreased significantly (p<0•05) whereas the abundance of the Amoebiasis pathway increased significantly in the FGR group (p<0•05). CONCLUSION In this study, we demonstrated that the occurrence of FGR is associated with the change of gut microbiota of pregnant women.
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Affiliation(s)
- Xin He
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing 100026, China
| | - Zhengpeng Li
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100039, China
| | - Xiaohui Li
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing 100026, China
| | - Huanying Zhao
- Genomics Research Platform, Core Facilities Center, Capital Medical University, Beijing 100069, China
| | - Yanan Hu
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing 100026, China
| | - Wenli Han
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing 100026, China
| | - Chen Wang
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing 100026, China
| | - Chenghong Yin
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing 100026, China.
| | - Yi Chen
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing 100026, China.
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22
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Effects of Additional Dietary Fiber Supplements on Pregnant Women with Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Studies. Nutrients 2022; 14:nu14214626. [PMID: 36364883 PMCID: PMC9658588 DOI: 10.3390/nu14214626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/20/2022] [Accepted: 10/26/2022] [Indexed: 11/06/2022] Open
Abstract
The efficacy of different types and doses of dietary fiber supplementation in the treatment of gestational diabetes (GDM) remains controversial. The purpose of this study is to investigate the effect of dietary fiber on blood glucose control in pregnant women with gestational diabetes mellitus, and further observe the effect on their blood lipids and pregnancy outcomes. We searched on Web of Science, PubMed, Embase, Scopus, and Cochrane, and included several articles on additional fortification with dietary fiber for gestational diabetes interventions. This meta-analysis included 8 trials. We found that additional dietary fiber supplements significantly reduced fasting glucose (Hedges’g = −0.3; 95% CI [−0.49, −0.1]), two-hour postprandial glucose (Hedges’g = −0.69; 95% CI [−0.88, −0.51]), glycated hemoglobin (Hedges’g = −0.5; 95% CI [−0.68, −0.31]), TC (Hedges’g = −0.44; 95% CI [−0.69, −0.19]), TG (Hedges’g = −0.3; 95% CI [−0.4, −0.2]) and LDL-C (Hedges’g = −0.48; 95% CI [−0.63, −0.33]). It also significantly reduced preterm delivery (Hedges’g = 0.4, 95% CI [0.19~0.84]), cesarean delivery (Hedges’g = 0.6; 95% CI [0.37~0.97]), fetal distress (Hedges’g = 0.51; 95% CI [0.22~1.19]), and neonatal weight (Hedges’g = −0.17; 95% CI [−0.27~−0.07]). In a subgroup analysis comparing dietary fiber type and dose, insoluble dietary fiber was more effective than soluble dietary fiber in reducing fasting glucose (Hedges’g = −0.44; 95% CI [−0.52, −0.35]). ≥12 g fiber per day may be more effective in improving glycemic lipid and pregnancy outcomes than <12 g/day, but the difference was not statistically significant. In conclusion, our meta-analysis showed that dietary fiber supplementation significantly improved glycolipid metabolism and pregnancy outcomes in gestational diabetes. Dietary fiber may be considered adjunctive therapy for gestational diabetes, and an additional supplement with insoluble dietary fiber is more recommended for those with poor fasting glucose. However, more high-quality studies are needed on the further effect of fiber type and the dose-effect relationship.
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Mao X, Peng X, Pan Q, Zhao X, Yu Z, Xu D. Uterine Fibroid Patients Reveal Alterations in the Gut Microbiome. Front Cell Infect Microbiol 2022; 12:863594. [PMID: 35646718 PMCID: PMC9131877 DOI: 10.3389/fcimb.2022.863594] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 03/29/2022] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota is associated with reproductive disorders in multiple ways. This research investigated possible differences in gut microbiome compositions between patients with uterine fibroids (UFs) and healthy control subjects in order to further provide new insight into its etiology. Stool samples were collected from 85 participants, including 42 UF patients (case group) and 43 control subjects (control group). The gut microbiota was examined with 16S rRNA quantitative arrays and bioinformatics analysis. The α-diversity in patients with UFs was significantly lower than that of healthy controls and negatively correlated with the number of tumorigeneses. The microbial composition of the UF patients deviated from the cluster of healthy controls. Stool samples from patients with UFs exhibited significant alterations in terms of multiple bacterial phyla, such as Firmicutes, Proteobacteria, Actinobacteria, and Verrucomicrobia. In differential abundance analysis, some bacteria species were shown to be downregulated (e.g., Bifidobacteria scardovii, Ligilactobacillus saerimneri, and Lactococcus raffinolactis) and upregulated (e.g., Pseudomonas stutzeri and Prevotella amnii). Furthermore, the microbial interactions and networks in UFs exhibited lower connectivity and complexity as well as higher clustering property compared to the controls. Taken together, it is possible that gut microbiota dysbiosis has the potential as a risk factor. This study found that UFs are associated with alterations of the gut microbiome diversity and community network connectivity. It provides a new direction to further explore the host–gut microbiota interplay and to develop management and prevention in UF pathogenesis.
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Affiliation(s)
- Xuetao Mao
- Department of Gynecology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Xuan Peng
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
| | - Qiong Pan
- Department of Gynecology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Xingping Zhao
- Department of Gynecology, The Third Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Zheng Yu, ; Dabao Xu, ; Xingping Zhao,
| | - Zheng Yu
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- *Correspondence: Zheng Yu, ; Dabao Xu, ; Xingping Zhao,
| | - Dabao Xu
- Department of Gynecology, The Third Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Zheng Yu, ; Dabao Xu, ; Xingping Zhao,
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24
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Liu ZZ, Sun JH, Wang WJ. Gut microbiota in gastrointestinal diseases during pregnancy. World J Clin Cases 2022; 10:2976-2989. [PMID: 35647135 PMCID: PMC9082698 DOI: 10.12998/wjcc.v10.i10.2976] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 07/18/2021] [Accepted: 03/07/2022] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota (GM) is a micro-ecosystem composed of all microorganisms in the human intestine. The interaction between GM and the host plays an important role in maintaining normal physiological functions in the host. Dysbiosis of the GM may cause various diseases. GM has been demonstrated to be associated with human health and disease, and changes during individual development and disease. Pregnancy is a complicated physiological process. Hormones, the immune system, metabolism, and GM undergo drastic changes during pregnancy. Gastrointestinal diseases during pregnancy, such as hepatitis, intrahepatic cholestasis of pregnancy, and pre-eclampsia, can affect both maternal and fetal health. The dysregulation of GM during pregnancy may lead to a variety of diseases, including gastrointestinal diseases. Herein, we review recent research articles on GM in pregnancy-related gastrointestinal diseases, discuss the interaction of the GM with the host under normal physiological conditions, gastrointestinal diseases, and pregnancy-specific disorders. As more attention is paid to reproductive health, the pathogenic mechanism of GM in gastrointestinal diseases during pregnancy will be further studied to provide a theoretical basis for the use of probiotics to treat these diseases.
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Affiliation(s)
- Zhong-Zhen Liu
- BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China
| | - Jing-Hua Sun
- BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Wen-Jing Wang
- BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China
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25
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Liu H, Li X, Zhu Y, Huang Y, Zhang Q, Lin S, Fang C, Li L, Lv Y, Mei W, Peng X, Yin J, Liu L. Effect of Plant-Derived n-3 Polyunsaturated Fatty Acids on Blood Lipids and Gut Microbiota: A Double-Blind Randomized Controlled Trial. Front Nutr 2022; 9:830960. [PMID: 35223959 PMCID: PMC8873928 DOI: 10.3389/fnut.2022.830960] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 01/21/2022] [Indexed: 12/29/2022] Open
Abstract
Background Several cardioprotective mechanisms attributed to n-3 polyunsaturated fatty acids (PUFAs) have been widely documented. Significant interest has recently focused on the role of human gut microbiota in metabolic disorders. However, the role of plant-derived n-3 PUFAs on blood lipid profiles is controversial and the effect on gut microbiota is still unclear. Objectives We aimed to perform a double-blind randomized controlled trial to test the effect of plant-derived n-3 PUFAs on the blood lipids and gut microbiota of patients with marginal hyperlipidemia. Methods According to the inclusion and exclusion criteria, 75 participants with marginal hyperlipidemia were randomly assigned to the intervention group (supplied with n-3 PUFA-enriched plant oil) or control group (supplied with corn oil), respectively, for a 3-month treatment. Participants and assessors were blinded to the allocation. The primary outcomes of the trial were the changes in serum lipid levels. Secondary outcomes were changes in gut microbiota and metabolites. For the primary outcomes, we conducted both an intent-to-treat (ITT) analysis and a per protocol (PP) analysis. For the secondary outcomes, we only conducted the PP analysis among the participants who provided fecal sample. Results Fifty-one participants completed the trial. Relative to the control group, the n-3 PUFA supplementation resulted in significant reduction in total cholesterol (TC) levels (−0.43 mmol/L, 95% CI−0.84 to−0.01 mmol/L, P < 0.05). The n-3 PUFA supplementation was also associated with significantly increased relative abundance of Bacteroidetes in phylum level (P < 0.01; false discovery rate (FDR) corrected p = 0.11), and decreased the ratio between Firmicutes and Bacteroidetes (P < 0.05; FDR corrected p = 0.16). At genus level, the intervention of plant derived n-3 PUFAs resulted in a significant decrease in relative abundance of Phascolarctobacterium (P < 0.01; FDR corrected p = 0.18) and Veillonella (P < 0.01; FDR corrected p = 0.18) after the intervention. Conclusions Our results demonstrated that plant-derived n-3 PUFAs beneficially affected the serum levels of TC and decreased the ratio between Firmicutes and Bacteroidetes during the 12-week intervention period, which might confer advantageous consequences for lipid metabolism and intestinal health.
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Affiliation(s)
- Hongjie Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoqin Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yalun Zhu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yue Huang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qin Zhang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shan Lin
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Can Fang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Linyan Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanling Lv
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenhua Mei
- Zhuhai Center for Disease Control and Prevention, Zhuhai, China
| | - Xiaolin Peng
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Shenzhen Nanshan Centre for Chronic Disease Control, Shenzhen, China
| | - Jiawei Yin
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Jiawei Yin
| | - Liegang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Liegang Liu
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26
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Preterm Labor, a Syndrome Attributed to the Combination of External and Internal Factors. MATERNAL-FETAL MEDICINE 2022. [DOI: 10.1097/fm9.0000000000000136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Yao Y, Cai X, Ye Y, Wang F, Chen F, Zheng C. The Role of Microbiota in Infant Health: From Early Life to Adulthood. Front Immunol 2021; 12:708472. [PMID: 34691021 PMCID: PMC8529064 DOI: 10.3389/fimmu.2021.708472] [Citation(s) in RCA: 130] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 09/17/2021] [Indexed: 12/11/2022] Open
Abstract
From early life to adulthood, the microbiota play a crucial role in the health of the infant. The microbiota in early life are not only a key regulator of infant health but also associated with long-term health. Pregnancy to early life is the golden time for the establishment of the infant microbiota, which is affected by both environmental and genetic factors. Recently, there is an explosion of the studies on the role of microbiota in human diseases, but the application to disease or health is relatively limited because many aspects of human microbiota remain controversial, especially about the infant microbiota. Therefore, a critical and conclusive review is necessary to understand fully the relationship between the microbiota and the health of infant. In this article, we introduce in detail the role of microbiota in the infant from pregnancy to early life to long-term health. The main contents of this article include the relationship between the maternal microbiota and adverse pregnancy outcomes, the establishment of the neonatal microbiota during perinatal period and early life, the composition of the infant gut microbiota, the prediction of the microbiota for long-term health, and the future study directions of microbiota.
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Affiliation(s)
- Yao Yao
- Department of Pharmacy, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China
| | - Xiaoyu Cai
- Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou, China
| | - Yiqing Ye
- Department of Pharmacy, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China
| | - Fengmei Wang
- Department of Pharmacy, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China
| | - Fengying Chen
- Department of Pharmacy, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China
| | - Caihong Zheng
- Department of Pharmacy, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China
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29
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Ansari A, Bose S, You Y, Park S, Kim Y. Molecular Mechanism of Microbiota Metabolites in Preterm Birth: Pathological and Therapeutic Insights. Int J Mol Sci 2021; 22:8145. [PMID: 34360908 PMCID: PMC8347546 DOI: 10.3390/ijms22158145] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/24/2021] [Accepted: 07/26/2021] [Indexed: 12/11/2022] Open
Abstract
Preterm birth (PTB) refers to the birth of infants before 37 weeks of gestation and is a challenging issue worldwide. Evidence reveals that PTB is a multifactorial dysregulation mediated by a complex molecular mechanism. Thus, a better understanding of the complex molecular mechanisms underlying PTB is a prerequisite to explore effective therapeutic approaches. During early pregnancy, various physiological and metabolic changes occur as a result of endocrine and immune metabolism. The microbiota controls the physiological and metabolic mechanism of the host homeostasis, and dysbiosis of maternal microbial homeostasis dysregulates the mechanistic of fetal developmental processes and directly affects the birth outcome. Accumulating evidence indicates that metabolic dysregulation in the maternal or fetal membranes stimulates the inflammatory cytokines, which may positively progress the PTB. Although labour is regarded as an inflammatory process, it is still unclear how microbial dysbiosis could regulate the molecular mechanism of PTB. In this review based on recent research, we focused on both the pathological and therapeutic contribution of microbiota-generated metabolites to PTB and the possible molecular mechanisms.
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Affiliation(s)
- AbuZar Ansari
- Department of Obstetrics and Gynecology, Ewha Medical Research Institute, College of Medicine, Ewha Womans University, Mokdong Hospital, Seoul 07985, Korea; (A.A.); (Y.Y.); (S.P.)
| | - Shambhunath Bose
- Department of Bioscience, Sri Sathya Sai University for Human Excellence, Navanihal, Okali Post, Kamalapur, Kalaburagi, Karnataka 585313, India;
| | - Youngah You
- Department of Obstetrics and Gynecology, Ewha Medical Research Institute, College of Medicine, Ewha Womans University, Mokdong Hospital, Seoul 07985, Korea; (A.A.); (Y.Y.); (S.P.)
| | - Sunwha Park
- Department of Obstetrics and Gynecology, Ewha Medical Research Institute, College of Medicine, Ewha Womans University, Mokdong Hospital, Seoul 07985, Korea; (A.A.); (Y.Y.); (S.P.)
| | - Youngju Kim
- Department of Obstetrics and Gynecology, Ewha Medical Research Institute, College of Medicine, Ewha Womans University, Mokdong Hospital, Seoul 07985, Korea; (A.A.); (Y.Y.); (S.P.)
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Ronde E, Reiss IKM, Hankemeier T, De Meij TG, Frerichs N, Schoenmakers S. The Potential of Metabolomic Analyses as Predictive Biomarkers of Preterm Delivery: A Systematic Review. Front Endocrinol (Lausanne) 2021; 12:668417. [PMID: 34552554 PMCID: PMC8451156 DOI: 10.3389/fendo.2021.668417] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 07/08/2021] [Indexed: 11/27/2022] Open
Abstract
SCOPE as the leading cause of perinatal mortality and morbidity worldwide, the impact of premature delivery is undisputable. Thus far, non-invasive, cost-efficient and accurate biochemical markers to predict preterm delivery are scarce. The aim of this systematic review is to investigate the potential of non-invasive metabolomic biomarkers for the prediction of preterm delivery. METHODS AND RESULTS Databases were systematically searched from March 2019 up to May 2020 resulting in 4062 articles, of which 45 were retrieved for full-text assessment. The resulting metabolites used for further analyses, such as ferritin, prostaglandin and different vitamins were obtained from different human anatomical compartments or sources (vaginal fluid, serum, urine and umbilical cord) and compared between groups of women with preterm and term delivery. None of the reported metabolites showed uniform results, however, a combination of metabolomics biomarkers may have potential to predict preterm delivery and need to be evaluated in future studies.
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Affiliation(s)
- Emma Ronde
- Division of Obstetrics and Prenatal Diagnosis, Erasmus University Medical Centre, Rotterdam, Netherlands
- *Correspondence: Emma Ronde,
| | - Irwin K. M. Reiss
- Department of Pediatrics, Division of Neonatology, Erasmus University Medical Centre, Rotterdam, Netherlands
| | - Thomas Hankemeier
- Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands
| | - Tim G. De Meij
- Department of Pediatric Gastroenterology, Amsterdam University Medical Centre, Amsterdam, Netherlands
| | - Nina Frerichs
- Department of Pediatric Gastroenterology, Amsterdam University Medical Centre, Amsterdam, Netherlands
| | - Sam Schoenmakers
- Division of Obstetrics and Prenatal Diagnosis, Erasmus University Medical Centre, Rotterdam, Netherlands
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Gao B, Zhao X, Liu X, Yang X, Zhang A, Huang H, Liou YL, Xu D. Imbalance of the Gut Microbiota May Be Associated with Missed Abortions: A Perspective Study from a General Hospital of Hunan Province. J Immunol Res 2021; 2021:5571894. [PMID: 34966824 PMCID: PMC8712186 DOI: 10.1155/2021/5571894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 09/17/2021] [Accepted: 10/30/2021] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVE To conduct a preliminary investigation that shows the possible correlation between the change of gut microbiota and missed abortions (MAs), which further provides a new potential insight for the prevention and therapy of MAs. METHOD One hundred women, including 50 patients with MAs (case group) and 50 normal pregnant women (control group), were enrolled in the study. Fecal specimens were collected in the first trimester. Bacterial DNA was extracted, hybridized with primers of specific genes, and then detected by bacterial chip. The composition and the relative abundance of the gut microbiota were compared and analyzed. Furthermore, Kyoto Encyclopedia of Genes and Genomes enrichment analysis was used to explore the relative pathways. RESULTS (1) The α-diversity and β-diversity of the gut microbiota in patients with MAs were significantly lower than that those in normal pregnant women (P < 0.05). At the phylum level, Firmicutes, Proteobacteria, Actinomycetes, and Bacteroidetes accounted for the main proportion of intestinal flora in the 2 groups. Only Actinobacteria was high in the case group. Significant differences were found between the two groups at the phylum level (P < 0.05). Prevotella, Lactobacillus, and Paracoccus were significantly more abundant in the control group than in the case group at the genus level (P < 0.05). (2) KEGG pathway enrichment analysis found significant differences in 27 signaling pathways and metabolic pathways between the two groups of differentially expressed genes (all adjusted P < 0.05). (3) The positive rate of M. hominins (MH) detection in the control group was significantly higher in the MA group (χ 2 = 7.853, P = 0.004). CONCLUSION The high abundance of Actinobacteria in the MA group was the first time found and reported in the study. The dysbiosis of the gut microbiota correlates with MAs. This study provided insights into the potential change of gut microbiota of MAs and the potential underlying mechanisms through certain impaired lipid metabolism and aroused inflammation pathways. Comprehensive insights regarding gut microbiota may facilitate improved understanding and the development of novel therapeutic and preventive strategies for MAs.
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Affiliation(s)
- Bingsi Gao
- Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Rd, Changsha, 410013 Hunan, China
| | - Xingping Zhao
- Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Rd, Changsha, 410013 Hunan, China
| | - Xinyi Liu
- Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Rd, Changsha, 410013 Hunan, China
- Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Hospital, 53 Xiangchun Rd, Changsha, 410008 Hunan, China
| | - Xuan Yang
- Central South University, Xiangya School of Medicine, 172 Tongzipo Rd, Changsha, 410013 Hunan, China
| | - Aiqian Zhang
- Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Rd, Changsha, 410013 Hunan, China
| | - Huan Huang
- Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Rd, Changsha, 410013 Hunan, China
| | - Yu-ligh Liou
- Xiangya Medical Laboratory, Central South University, Changsha, Hunan 410078, China
- The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Dabao Xu
- Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Rd, Changsha, 410013 Hunan, China
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