肠道菌群及其代谢物和ART妊娠结局的相关性研究
The Correlation Study of Gut Microbiota and Its Metabolites with ART Pregnancy Outcomes
DOI: 10.12677/md.2025.154054, PDF,   
作者: 任士威：济宁医学院临床医学院(附属医院)，山东 济宁；郭 焕*：济宁医学院附属医院临床检验科，山东 济宁
关键词: 辅助生殖技术(ART)；肠道菌群；妊娠结局；Assisted Reproductive Technology (ART)； Gut Microbiota； Pregnancy Outcomes
摘要: 这篇论文综述了辅助生殖技术(ART)的进展及其对妊娠结果和胎儿发育的影响。文中强调不孕症的日益普遍，各种ART技术的发展及其对胚胎和胎儿健康潜在的影响。文章还探讨了母体肠道菌群及其代谢物对胚胎发育和妊娠结果的作用，指出ART可能导致母体肠道菌群及其代谢产物的变化，从而影响胎盘功能和胚胎发育能力。进一步研究了ART与母体肠道菌群及其代谢物通过调控机制影响胎盘功能及胚胎发育能力之间关系的重要性，以及这些关系对妊娠结局和胎儿发育的影响，对于进一步提高辅助生殖技术的成功率和胎儿健康具有重要的意义。
Abstract: This paper reviews the advancements in Assisted Reproductive Technology (ART) and its impact on pregnancy outcomes and fetal development. The article emphasizes the increasing prevalence of infertility, the development of various ART techniques, and their potential effects on embryo and fetal health. It also explores the role of maternal gut microbiota and its metabolites in embryo development and pregnancy outcomes, pointing out that ART may lead to changes in maternal gut microbiota and its metabolites, thereby affecting placental function and embryo development. The paper further investigates the importance of the relationship between ART, maternal gut microbiota, and its metabolites in regulating placental function and embryo development, and how these relationships impact pregnancy outcomes and fetal development. These findings are crucial for improving the success rate of ART and ensuring fetal health.
文章引用：任士威, 郭焕. 肠道菌群及其代谢物和ART妊娠结局的相关性研究[J]. 医学诊断, 2025, 15(4): 403-410. https://doi.org/10.12677/md.2025.154054

参考文献

[1] 马黔红. 辅助生殖技术的新进展[J]. 中国计划生育和妇产科, 2017, 9(1): 4-7.
[2] 乔杰. 人类辅助生殖技术的新进展[J]. 中国实用妇科与产科杂志, 2008(1): 33-34.
[3] Hu, L., Bu, Z., Huang, G., Sun, H., Deng, C. and Sun, Y. (2020) Assisted Reproductive Technology in China: Results Generated from Data Reporting System by CSRM from 2013 to 2016. Frontiers in Endocrinology (Lausanne), 11, Article No. 458. [Google Scholar] [CrossRef] [PubMed]
[4] Bai, F., Wang, D.Y., Fan, Y.J., Qiu, J., Wang, L., Dai, Y., et al. (2020) Assisted Reproductive Technology Service Availability, Efficacy and Safety in Mainland China: 2016. Human Reproduction, 35, 446-452. [Google Scholar] [CrossRef] [PubMed]
[5] Fleming, T.P., Velazquez, M.A. and Eckert, J.J. (2015) Embryos, Dohad and David Barker. Journal of Developmental Origins of Health and Disease, 6, 377-383. [Google Scholar] [CrossRef] [PubMed]
[6] Barker, D.J.P. (1995) The Fetal and Infant Origins of Disease. European Journal of Clinical Investigation, 25, 457-463. [Google Scholar] [CrossRef] [PubMed]
[7] Berntsen, S., Söderström-Anttila, V., Wennerholm, U., Laivuori, H., Loft, A., Oldereid, N.B., et al. (2019) The Health of Children Conceived by ART: “The Chicken or the Egg?”. Human Reproduction Update, 25, 137-158. [Google Scholar] [CrossRef] [PubMed]
[8] Vrooman, L.A. and Bartolomei, M.S. (2017) Can Assisted Reproductive Technologies Cause Adult-Onset Disease? Evidence from Human and Mouse. Reproductive Toxicology, 68, 72-84. [Google Scholar] [CrossRef] [PubMed]
[9] Feuer, S.K., Camarano, L. and Rinaudo, P.F. (2012) ART and Health: Clinical Outcomes and Insights on Molecular Mechanisms from Rodent Studies. Molecular Human Reproduction, 19, 189-204. [Google Scholar] [CrossRef] [PubMed]
[10] Maroufizadeh, S., Navid, B., Alizadeh, A., Amini, P., Almasi-Hashiani, A., Mohammadi, M., et al. (2019) Risk of Gestational Diabetes Mellitus Following Assisted Reproductive Technology: Systematic Review and Meta-Analysis of 59 Cohort Studies. The Journal of Maternal-Fetal & Neonatal Medicine, 34, 2731-2740. [Google Scholar] [CrossRef] [PubMed]
[11] Zhao, J., Yan, Y., Huang, X. and Li, Y. (2018) Do the Children Born after Assisted Reproductive Technology Have an Increased Risk of Birth Defects? A Systematic Review and Meta-Analysis. The Journal of Maternal-Fetal & Neonatal Medicine, 33, 322-333. [Google Scholar] [CrossRef] [PubMed]
[12] Bloise, E., Feuer, S.K. and Rinaudo, P.F. (2014) Comparative Intrauterine Development and Placental Function of ART Concepti: Implications for Human Reproductive Medicine and Animal Breeding. Human Reproduction Update, 20, 822-839. [Google Scholar] [CrossRef] [PubMed]
[13] Sender, R., Fuchs, S. and Milo, R. (2016) Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLOS Biology, 14, e1002533. [Google Scholar] [CrossRef] [PubMed]
[14] Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K.S., Manichanh, C., et al. (2010) A Human Gut Microbial Gene Catalogue Established by Metagenomic Sequencing. Nature, 464, 59-65. [Google Scholar] [CrossRef] [PubMed]
[15] La Rosa, P.S., Warner, B.B., Zhou, Y., Weinstock, G.M., Sodergren, E., Hall-Moore, C.M., et al. (2014) Patterned Progression of Bacterial Populations in the Premature Infant Gut. Proceedings of the National Academy of Sciences, 111, 12522-12527. [Google Scholar] [CrossRef] [PubMed]
[16] Korpela, K., Blakstad, E.W., Moltu, S.J., Strømmen, K., Nakstad, B., Rønnestad, A.E., et al. (2018) Intestinal Microbiota Development and Gestational Age in Preterm Neonates. Scientific Reports, 8, Article No. 2453. [Google Scholar] [CrossRef] [PubMed]
[17] Pattaroni, C., Watzenboeck, M.L., Schneidegger, S., Kieser, S., Wong, N.C., Bernasconi, E., et al. (2018) Early-Life Formation of the Microbial and Immunological Environment of the Human Airways. Cell Host & Microbe, 24, 857-865.e4. [Google Scholar] [CrossRef] [PubMed]
[18] Bäckhed, F., Roswall, J., Peng, Y., Feng, Q., Jia, H., Kovatcheva-Datchary, P., et al. (2015) Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host & Microbe, 17, 690-703. [Google Scholar] [CrossRef] [PubMed]
[19] Qi, X., Yun, C., Pang, Y. and Qiao, J. (2021) The Impact of the Gut Microbiota on the Reproductive and Metabolic Endocrine System. Gut Microbes, 13, 1-21. [Google Scholar] [CrossRef] [PubMed]
[20] Fleming, T.P., Watkins, A.J., Velazquez, M.A., Mathers, J.C., Prentice, A.M., Stephenson, J., et al. (2018) Origins of Lifetime Health around the Time of Conception: Causes and Consequences. The Lancet, 391, 1842-1852. [Google Scholar] [CrossRef] [PubMed]
[21] Nuriel-Ohayon, M., Neuman, H., Ziv, O., Belogolovski, A., Barsheshet, Y., Bloch, N., et al. (2019) Progesterone Increases Bifidobacterium Relative Abundance during Late Pregnancy. Cell Reports, 27, 730-736.e3. [Google Scholar] [CrossRef] [PubMed]
[22] Hansen, M., Kurinczuk, J.J., Bower, C. and Webb, S. (2002) The Risk of Major Birth Defects after Intracytoplasmic Sperm Injection and in Vitro Fertilization. New England Journal of Medicine, 346, 725-730. [Google Scholar] [CrossRef] [PubMed]
[23] Koenig, J.E., Spor, A., Scalfone, N., Fricker, A.D., Stombaugh, J., Knight, R., et al. (2010) Succession of Microbial Consortia in the Developing Infant Gut Microbiome. Proceedings of the National Academy of Sciences, 108, 4578-4585. [Google Scholar] [CrossRef] [PubMed]
[24] Li, Y., Chang, Q. and Mai, Q. (2023) Pregnancy and Neonatal Outcomes of Monozygotic Twins Resulting from Assisted Reproductive Technology: A 10-Year Retrospective Study. Reproductive Biology and Endocrinology, 21, Article No. 51. [Google Scholar] [CrossRef] [PubMed]
[25] Pandey, S., Shetty, A., Hamilton, M., Bhattacharya, S. and Maheshwari, A. (2012) Obstetric and Perinatal Outcomes in Singleton Pregnancies Resulting from IVF/ICSI: A Systematic Review and Meta-Analysis. Human Reproduction Update, 18, 485-503. [Google Scholar] [CrossRef] [PubMed]
[26] De la Calle, M., Bartha, J.L., García, L., Cuerva, M.J. and Ramiro-Cortijo, D. (2021) Women Aged over 40 with Twin Pregnancies Have a Higher Risk of Adverse Obstetrical Outcomes. International Journal of Environmental Research and Public Health, 18, Article No. 13117. [Google Scholar] [CrossRef] [PubMed]
[27] Wang, Y., Shi, H., Chen, L., Zheng, D., Long, X., Zhang, Y., et al. (2021) Absolute Risk of Adverse Obstetric Outcomes among Twin Pregnancies after in Vitro Fertilization by Maternal Age. JAMA Network Open, 4, e2123634. [Google Scholar] [CrossRef] [PubMed]
[28] Birth Characteristics in England and Wales (2017)
https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/livebirths/bulletins/birthcharacteristicsinenglandandwales/2017
[29] Giorgione, V., Melchiorre, K., O’Driscoll, J., Khalil, A., Sharma, R. and Thilaganathan, B. (2022) Maternal Echocardiographic Changes in Twin Pregnancies with and without Pre‐Eclampsia. Ultrasound in Obstetrics & Gynecology, 59, 619-626. [Google Scholar] [CrossRef] [PubMed]
[30] Giorgione, V., Briffa, C., Di Fabrizio, C., Bhate, R. and Khalil, A. (2021) Perinatal Outcomes of Small for Gestational Age in Twin Pregnancies: Twin vs. Singleton Charts. Journal of Clinical Medicine, 10, Article No. 643. [Google Scholar] [CrossRef] [PubMed]
[31] Carter, E.B., Bishop, K.C., Goetzinger, K.R., Tuuli, M.G. and Cahill, A.G. (2015) The Impact of Chorionicity on Maternal Pregnancy Outcomes. American Journal of Obstetrics and Gynecology, 213, 390.e1-390.e7. [Google Scholar] [CrossRef] [PubMed]
[32] Kilby, M., Gibson, J. and Ville, Y. (2018) Falling Perinatal Mortality in Twins in the UK: Organisational Success or Chance? BJOG: An International Journal of Obstetrics & Gynaecology, 126, 341-347. [Google Scholar] [CrossRef] [PubMed]
[33] Gibson, J.L., Castleman, J.S., Meher, S. and Kilby, M.D. (2019) Updated Guidance for the Management of Twin and Triplet Pregnancies from the National Institute for Health and Care Excellence Guidance, UK: What’s New That May Improve Perinatal Outcomes? Acta Obstetricia et Gynecologica Scandinavica, 99, 147-152. [Google Scholar] [CrossRef] [PubMed]
[34] Whittaker, M., Greatholder, I., Kilby, M.D. and Heazell, A.E.P. (2023) Risk Factors for Adverse Outcomes in Twin Pregnancies: A Narrative Review. The Journal of Maternal-Fetal & Neonatal Medicine, 36, Article ID: 2240467. [Google Scholar] [CrossRef] [PubMed]
[35] Basak, S., Das, R.K., Banerjee, A., Paul, S., Pathak, S. and Duttaroy, A.K. (2022) Maternal Obesity and Gut Microbiota Are Associated with Fetal Brain Development. Nutrients, 14, Article No. 4515. [Google Scholar] [CrossRef] [PubMed]
[36] Sajdel-Sulkowska, E.M. (2023) The Impact of Maternal Gut Microbiota during Pregnancy on Fetal Gut-Brain Axis Development and Life-Long Health Outcomes. Microorganisms, 11, Article No. 2199. [Google Scholar] [CrossRef] [PubMed]
[37] Koren, O., Goodrich, J.K., Cullender, T.C., Spor, A., Laitinen, K., Kling Bäckhed, H., et al. (2012) Host Remodeling of the Gut Microbiome and Metabolic Changes during Pregnancy. Cell, 150, 470-480. [Google Scholar] [CrossRef] [PubMed]
[38] García-Gómez, E., González-Pedrajo, B. and Camacho-Arroyo, I. (2013) Role of Sex Steroid Hormones in Bacterial-Host Interactions. BioMed Research International, 2013, Article ID: 928290. [Google Scholar] [CrossRef] [PubMed]
[39] Khalili, H. (2015) Risk of Inflammatory Bowel Disease with Oral Contraceptives and Menopausal Hormone Therapy: Current Evidence and Future Directions. Drug Safety, 39, 193-197. [Google Scholar] [CrossRef] [PubMed]
[40] 王方, 郑剑兰, 汪文雁, 等. 辅助生殖技术与妊娠期糖尿病孕产妇肠道菌群的特异表达[J]. 发育医学电子杂志, 2021, 9(2): 114-121.
[41] Org, E., Mehrabian, M., Parks, B.W., Shipkova, P., Liu, X., Drake, T.A., et al. (2016) Sex Differences and Hormonal Effects on Gut Microbiota Composition in Mice. Gut Microbes, 7, 313-322. [Google Scholar] [CrossRef] [PubMed]
[42] Ng, K.Y.B., Mingels, R., Morgan, H., Macklon, N. and Cheong, Y. (2017) In Vivo Oxygen, Temperature and Ph Dynamics in the Female Reproductive Tract and Their Importance in Human Conception: A Systematic Review. Human Reproduction Update, 24, 15-34. [Google Scholar] [CrossRef] [PubMed]
[43] Lau, E., Lee, C., Li, B. and Pierro, A. (2021) Endoplasmic Reticulum Stress in the Acute Intestinal Epithelial Injury of Necrotizing Enterocolitis. Pediatric Surgery International, 37, 1151-1160. [Google Scholar] [CrossRef] [PubMed]
[44] Nakashima, A., Cheng, S., Kusabiraki, T., Motomura, K., Aoki, A., Ushijima, A., et al. (2019) Endoplasmic Reticulum Stress Disrupts Lysosomal Homeostasis and Induces Blockade of Autophagic Flux in Human Trophoblasts. Scientific Reports, 9, Article No. 11466. [Google Scholar] [CrossRef] [PubMed]
[45] Lopez-Tello, J., Schofield, Z., Kiu, R., Dalby, M.J., van Sinderen, D., Le Gall, G., et al. (2022) Maternal Gut Microbiota Bifidobacterium Promotes Placental Morphogenesis, Nutrient Transport and Fetal Growth in Mice. Cellular and Molecular Life Sciences, 79, Article No. 386. [Google Scholar] [CrossRef] [PubMed]
[46] Ke, X., You, K., Pichaud, M., Haiser, H.J., Graham, D.B., Vlamakis, H., et al. (2021) Gut Bacterial Metabolites Modulate Endoplasmic Reticulum Stress. Genome Biology, 22, Article No. 292. [Google Scholar] [CrossRef] [PubMed]
[47] Tao, Z., Chen, Y., He, F., Tang, J., Zhan, L., Hu, H., et al. (2023) Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction. Microbiology Spectrum, 11, e00076-23. [Google Scholar] [CrossRef] [PubMed]
[48] Li, A., Li, F., Song, W., Lei, Z., Sha, Q., Liu, S., et al. (2023) Gut Microbiota-Bile Acid‐Vitamin D Axis Plays an Important Role in Determining Oocyte Quality and Embryonic Development. Clinical and Translational Medicine, 13, e1236. [Google Scholar] [CrossRef] [PubMed]