Ecology, Evolution, Behavior and Systematics; Health Professions (miscellaneous); Agricultural and Biological Sciences (miscellaneous)
Abstract :
[en] Maternal obesity constitutes a risk factor for gestational complications and adverse pregnancy outcomes. While insulin resistance, metabolic syndrome, and inflammation are recognized contributors, the clinical heterogeneity among these disorders suggests the involvement of systemic, cross-organ interactions. Among these, the gut-placenta axis has become a mechanistic bridge linking maternal metabolism with placental development and fetal health. This review examines the evolution of the gut-placenta axis over the past 50 years and looks forward to its clinical translation in the next 50 years. The obesity-related gut microbiota alterations and their associations with placental dysfunction are summarized. We propose that obesity-induced gut dysbiosis establishes a shared pathophysiological foundation, or “common soil”, characterized by microbial translocation, inflammation at the maternal-fetal interface, and abnormal placental vascularization. From this shared foundation emerge diseases including gestational diabetes mellitus (GDM), preeclampsia (PE), and fetal growth restriction (FGR). Current microbiota-targeted interventions have demonstrated partial metabolic improvements but limited clinical efficacy, highlighting the need for better experimental models, optimal timing, and targeted delivery. Ultimately, targeting this common soil may enable a transition from association to prevention, and transform obesity-related pregnancy complications from adverse outcomes into preventable conditions.
Precision for document type :
Review article
Disciplines :
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Wo, Yeqianli ; Université de Liège - ULiège > TERRA Research Centre > Animal Sciences (AS) ; State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
Zhong, Ruqing; State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
Wang, Leli; Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
He, Jianhua; College of Animal Science and Technology, Hunan Agricultural University, Changsha, China
Schroyen, Martine ; Université de Liège - ULiège > TERRA Research Centre > Animal Sciences (AS)
O'Reilly, Sharleen; School of Agriculture and Food Science, University College Dublin, Belfield, Ireland
Chen, Liang; State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
Zhang, Hongfu; State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
Language :
English
Title :
From gut dysbiosis to placental dysfunction in maternal obesity: A common soil for gestational complications
Publication date :
19 January 2026
Journal title :
The Innovation Life
eISSN :
2959-8761
Publisher :
Innovation Press
Volume :
4
Issue :
1
Pages :
100185
Peer reviewed :
Peer Reviewed verified by ORBi
Funding text :
This study was supported by the National Natural Science Foundation of China (U22A20515, 32573254), Basal Research Fund for State Key Laboratory of Animal Nutrition and Feeding (2004DA125184G2402), and Agricultural Science and Technology Innovation Program (ASTIPIAS07). The funders had no role in study design, data collection andanalysis, decision to publish, or preparation of the manuscript.
Johansson K., Bodnar L. M., Stephansson O., et al. (2024). Safety of low weight gain or weight loss in pregnancies with class 1, 2, and 3 obesity: A population-based cohort study. Lancet. 403:1472−1481. DOI:10.1016/S0140-6736(24)00255-1
Collaborators G. A. B. (2025). Global, regional, and national prevalence of adult overweight and obesity, 1990-2021, with forecasts to 2050: A forecasting study for the global burden of disease study 2021. Lancet. 405:813−838. DOI:10.1016/S0140-6736(25)00355-1
Shirvanifar M., Ahlqvist V. H., Lundberg M., et al. (2024). Adverse pregnancy outcomes attributable to overweight and obesity across maternal birth regions: A Swedish population-based cohort study. Lancet Public Health 9:e776−e786. DOI:10. 1016/s2468-2667(24)00188-9
Voerman E., Santos S., Inskip H., et al. (2019). Association of gestational weight gain with adverse maternal and infant outcomes. JAMA 321:1702−1715. DOI:10.1001/ jama.2019.3820
Weir T. L., Majumder M. and Glastras S. J. (2024). A systematic review of the effects of maternal obesity on neonatal outcomes in women with gestational diabetes. Obes. Rev. 25:e13747. DOI:10.1111/obr.13747
Atta N., Ezeoke A., Petry C. J., et al. (2024). Associations of high bmi and excessive gestational weight gain with pregnancy outcomes in women with type 1 diabetes: A systematic review and meta-analysis. Diabetes Care 47:1855−1868. DOI:10.2337/ dc24-0725
Brombach C., Tong W. and Giussani D. A. (2022). Maternal obesity: New placental paradigms unfolded. Trends Mol. Med. 28:823−835. DOI:10.1016/j.molmed.2022.05. 013
Catalano P. M. and Shankar K. (2017). Obesity and pregnancy: Mechanisms of short term and long term adverse consequences for mother and child. BMJ 356:j1. DOI:10. 1136/bmj.j1
Hampton T. (2020). Do gut bacteria play a role in preeclampsia. JAMA 323:2120−2121. DOI:10.1001/jama.2020.4755
Pronovost G. N., Yu K. B., Coley-O'Rourke E. J. L., et al. (2023). The maternal microbiome promotes placental development in mice. Sci. Adv. 9:eadk1887. DOI:10. 1126/sciadv.adk1887
Wu J., Zheng X., Wu C., et al. (2025). Melatonin alleviates high temperature exposure induced fetal growth restriction via the gut-placenta-fetus axis in pregnant mice. J. Adv. Res. 68:131−146. DOI:10.1016/j.jare.2024.02.014
Fisman E. Z., Westermeier F. and Santulli G. (2025). A new kid in town: Cardiovascular diabetology-endocrinology reports. Cardiovasc. Diabetol. 24:30. DOI:10.1186/s12933-025-02602-1
Hibler E. A. and Lloyd-Jones D. M. (2021). Addressing the "common soil" of risk factors for cardiovascular disease and cancer. JACC CardioOncol. 3:59−61. DOI:10. 1016/j.jaccao.2021.02.003
Tian Z., Zhang X., Yao G., et al. (2024). Intestinal flora and pregnancy complications: Current insights and future prospects. Imeta 3:e167. DOI:10.1002/imt2.167
Miller J. K. and Burns J. (1970). Histopathology of Listeria monocytogenes after oral feeding to mice. Appl. Microbiol. 19:772−775. DOI:10.1128/am.19.5.772-775.1970
Wetli C. V., Roldan E. O. and Fojaco R. M. (1983). Listeriosis as a cause of maternal death: An obstetric complication of the acquired immunodeficiency syndrome (AIDS). Am. J. Obstet. Gynecol. 147:7−9. DOI:10.1016/0002-9378(83)90074-1
Anderson G. D. (1975). Listeria monocytogenes septicemia in pregnancy. Obstet. Gynecol. 46:102−104. DOI:10.1097/00006250-197507000-00021
Li Y., Shibata Y., Zhang L., et al. (2011). Periodontal pathogen Aggregatibacter actinomycetemcomitans LPS induces mitochondria-dependent-apoptosis in human placental trophoblasts. Placenta 32:11−19. DOI:10.1016/j.placenta.2010.10. 007
Equils O., Uh A., Blue C., et al. (2007). 100: Lipopolysaccharide (LPS) stimulation induces corticotropin releasing hormone (CRH) expression through MyD88 in trophoblast cells. Am. J. Obstet. Gynecol. 197:S42. DOI:10.1016/j.ajog.2007.10.111
Aagaard K., Ma J., Antony K. M., et al. (2014). The placenta harbors a unique microbiome. Sci. Transl. Med. 6:237ra265. DOI:10.1126/scitranslmed.3008599
Kennedy K. M., de Goffau M. C., Perez-Muñoz M. E., et al. (2023). Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies. Nature 613:639−649. DOI:10.1038/s41586-022-05546-8
Morffy Smith C. D., Gong M., Andrew A. K., et al. (2019). Composition of the gut microbiota transcends genetic determinants of malaria infection severity and influences pregnancy outcome. EBioMedicine 44:639−655. DOI:10.1016/j.ebiom. 2019.05.052
Chen X., Li P., Liu M., et al. (2020). Gut dysbiosis induces the development of preeclampsia through bacterial translocation. Gut 69:513−522. DOI:10.1136/gutjnl-2019-319101
Jin J., Gao L., Zou X., et al. (2022). Gut dysbiosis promotes preeclampsia by regulating macrophages and trophoblasts. Circ. Res. 131:492−506. DOI:10.1161/ CIRCRESAHA.122.320771
Huang S., Chen J., Cui Z., et al. (2023). Lachnospiraceae-derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus. Sci. Adv. 9:eadi7337. DOI:10.1126/sciadv.adi7337
Argaw-Denboba A., Schmidt T. S. B., Di Giacomo M., et al. (2024). Paternal microbiome perturbations impact offspring fitness. Nature 629:652−659. DOI:10. 1038/s41586-024-07336-w
Gray T. K., Lowe W. and Lester G. E. (1981). Vitamin D and pregnancy: The maternal-fetal metabolism of vitamin D. Endocr. Rev. 2:264−274. DOI:10.1210/edrv-2-3-264
Yaron Y., Lessing J. B. and Peyser M. R. (1992). Abruptio placentae associated with perforated appendicitis and generalized peritonitis. Am. J. Obstet. Gynecol. 166:14−15. DOI:10.1016/0002-9378(92)91818-u
Disson O., Grayo S., Huillet E., et al. (2008). Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis. Nature 455:1114−1118. DOI:10.1038/nature07303
Lecuit M., Nelson D. M., Smith S. D., et al. (2004). Targeting and crossing of the human maternofetal barrier by Listeria monocytogenes: Role of internalin interaction with trophoblast E-cadherin. Proc. Natl. Acad. Sci. USA 101:6152−6157. DOI:10.1073/pnas.0401434101
Yeganegi M., Watson C. S., Martins A., et al. (2009). Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: Implications for treatment of bacterial vaginosis and prevention of preterm labor. Am. J. Obstet. Gynecol. 200:532.e531−532.e538. DOI:10.1016/j.ajog.2008.12.032
Yang S., Li W., Challis J. R. G., et al. (2014). Probiotic Lactobacillus rhamnosus GR-1 supernatant prevents lipopolysaccharide-induced preterm birth and reduces inflammation in pregnant CD-1 mice. Am. J. Obstet. Gynecol. 211:44.e41−44.e12. DOI:10.1016/j.ajog.2014.01.029
Gomez-Arango L. F., Barrett H. L., McIntyre H. D., et al. (2017). Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant women. Sci. Rep. 7:2860. DOI:10.1038/s41598-017-03066-4
Gil A., Rueda R., Ozanne S. E., et al. (2020). Is there evidence for bacterial transfer via the placenta and any role in the colonization of the infant gut. - A systematic review. Crit. Rev. Microbiol. 46:493−507. DOI:10.1080/1040841x.2020.1800587
Chen Y., Ou Z., Pang M., et al. (2023). Extracellular vesicles derived from Akkermansia muciniphila promote placentation and mitigate preeclampsia in a mouse model. J. Extracell. Vesicles 12:e12328. DOI:10.1002/jev2.12328
Xie Y., Zhao F., Wang Y., et al. (2024). Fetal growth restriction induced by maternal gal-3 deficiency is associated with altered gut-placenta axis. Cell Death Dis. 15:575. DOI:10.1038/s41419-024-06962-6
Zhang H., Zha X., Zhang B., et al. (2024). Gut microbiota contributes to bisphenol A-induced maternal intestinal and placental apoptosis, oxidative stress, and fetal growth restriction in pregnant ewe model by regulating gut-placental axis. Microbiome 12:28. DOI:10.1186/s40168-024-01749-5
Wang J., Gao Y., Ren S., et al. (2024). Gut microbiota-derived trimethylamine N-Oxide: A novel target for the treatment of preeclampsia. Gut Microbes 16:2311888. DOI:10.1080/19490976.2024.2311888
Feng C., Wu Y., Zhang X., et al. (2025). Maternal milk fat globule membrane enriched gut L. murinus and circulating SCFAs to improve placental efficiency and fetal development in intrauterine growth restricted mice model. Gut Microbes 17:2449095. DOI:10.1080/19490976.2024.2449095
Karvas R. M., Zemke J. E., Ali S. S., et al. (2023). 3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages. Cell Stem Cell 30:1148−1165.e1147. DOI:10.1016/j.stem.2023.08.005
Deng Z., Dai F., Wang R., et al. (2024). Organ-on-a-chip: Future of female reproductive pathophysiological models. J. Nanobiotechnology. 22:455. DOI:10. 1186/s12951-024-02651-w
Mao Q., Ye Q., Xu Y., et al. (2023). Murine trophoblast organoids as a model for trophoblast development and CRISPR-Cas9 screening. Dev. Cell. 58:2992−3008.e2997. DOI:10.1016/j.devcel.2023.11.007
Hori T., Okae H., Shibata S., et al. (2024). Trophoblast stem cell-based organoid models of the human placental barrier. Nat. Commun. 15:962. DOI:10.1038/s41467-024-45279-y
Wollert T., Pasche B., Rochon M., et al. (2007). Extending the host range of Listeria monocytogenes by rational protein design. Cell 129:891−902. DOI:10.1016/j.cell. 2007.03.049
Arutyunyan A., Roberts K., Troulé K., et al. (2023). Spatial multiomics map of trophoblast development in early pregnancy. Nature 616:143−151. DOI:10.1038/ s41586-023-05869-0
Abbas Y., Turco M. Y., Burton G. J., et al. (2020). Investigation of human trophoblast invasion in vitro. Hum. Reprod. Update 26:501−513. DOI:10.1093/humupd/dmaa017
Ma T., Yang S. T. and Kniss D. A. (1999). Development of an in vitro human placenta model by the cultivation of human trophoblasts in a fiber-based bioreactor system. Tissue Eng. 5:91−102. DOI:10.1089/ten.1999.5.91
Vento-Tormo R., Efremova M., Botting R. A., et al. (2018). Single-cell reconstruction of the early maternal-fetal interface in humans. Nature 563:347−353. DOI:10.1038/ s41586-018-0698-6
Turco M. Y., Gardner L., Kay R. G., et al. (2018). Trophoblast organoids as a model for maternal-fetal interactions during human placentation. Nature 564:263−267. DOI:10.1038/s41586-018-0753-3
Sheridan M. A., Fernando R. C., Gardner L., et al. (2020). Establishment and differentiation of long-term trophoblast organoid cultures from the human placenta. Nat. Protoc. 15:3441−3463. DOI:10.1038/s41596-020-0381-x
Greenbaum S., Averbukh I., Soon E., et al. (2023). A spatially resolved timeline of the human maternal-fetal interface. Nature 619:595−605. DOI:10.1038/s41586-023-06298-9
Wang S., Liu Y., Qin S., et al. (2022). Composition of maternal circulating short-chain fatty acids in gestational diabetes mellitus and their associations with placental metabolism. Nutrients 14:3727. DOI:10.3390/nu14183727
Tao Z., Chen Y., He F., et al. (2023). Alterations in the gut microbiome and metabolisms in pregnancies with fetal growth restriction. Microbiol. Spectr. 11:e0007623. DOI:10.1128/spectrum.00076-23
Xiong L., Azad M. A. K., Liu Y., et al. (2024). Intrauterine growth restriction affects colonic barrier function via regulating the Nrf2/Keap1 and TLR4-NF-κB/ERK pathways and altering colonic microbiome and metabolome homeostasis in growing-finishing pigs. Antioxidants 13:283. DOI:10.3390/antiox13030283
Liu B., Zhu X., Cui Y., et al. (2021). Consumption of dietary fiber from different sources during pregnancy alters sow gut microbiota and improves performance and reduces inflammation in sows and piglets. mSystems 6:e00591−00520. DOI:10. 1128/mSystems.00591-20
Brantsaeter A. L., Myhre R., Haugen M., et al. (2011). Intake of probiotic food and risk of preeclampsia in primiparous women: The Norwegian mother and child cohort study. Am. J. Epidemiol. 174:807−815. DOI:10.1093/aje/kwr168
Nordqvist M., Jacobsson B., Brantsæter A., et al. (2018). Timing of probiotic milk consumption during pregnancy and effects on the incidence of preeclampsia and preterm delivery: A prospective observational cohort study in Norway. BMJ Open 8:e018021. DOI:10.1136/bmjopen-2017-018021
Davidson S. J., Barrett H. L., Price S. A., et al. (2021). Probiotics for preventing gestational diabetes. Cochrane Database. Syst. Rev. 4:CD009951. DOI:10.1002/ 14651858.CD009951.pub3
Nachum Z., Perlitz Y., Shavit L. Y., et al. (2024). The effect of oral probiotics on glycemic control of women with gestational diabetes mellitus-a multicenter, randomized, double-blind, placebo-controlled trial. Am. J. Obstet. Gynecol. MFM 6:101224. DOI:10.1016/j.ajogmf.2023.101224
Pellonperä O., Mokkala K., Houttu N., et al. (2019). Efficacy of fish oil and/or probiotic intervention on the incidence of gestational diabetes mellitus in an at-risk group of overweight and obese women: A randomized, placebo-controlled, double-blind clinical trial. Diabetes Care 42:1009−1017. DOI:10.2337/dc18-2591
Rautava S., Collado M. C., Salminen S., et al. (2012). Probiotics modulate host-microbe interaction in the placenta and fetal gut: A randomized, double-blind, placebo-controlled trial. Neonatology 102:178−184. DOI:10.1159/000339182
Callaway L. K., McIntyre H. D., Barrett H. L., et al. (2019). Probiotics for the prevention of gestational diabetes mellitus in overweight and obese women: Findings from the SPRING double-blind randomized controlled trial. Diabetes Care 42:364−371. DOI:10. 2337/dc18-2248
Mokkala K., Paulin N., Houttu N., et al. (2021). Metagenomics analysis of gut microbiota in response to diet intervention and gestational diabetes in overweight and obese women: A randomised, double-blind, placebo-controlled clinical trial. Gut 70:309−318. DOI:10.1136/gutjnl-2020-321643
Cui Z., Wang S., Niu J., et al. (2024). Bifidobacterium species serve as key gut microbiome regulators after intervention in gestational diabetes mellitus. BMC Microbiol. 24:520. DOI:10.1186/s12866-024-03680-z
Vanda R., Dastani T., Taghavi S. A., et al. (2024). Pregnancy outcomes in pregnant women taking oral probiotic undergoing cerclage compared to placebo: Two blinded randomized controlled trial. BMC Pregnancy and Childb. 24:311. DOI:10.1186/ s12884-024-06496-x
Movaghar R., Abbasalizadeh S., Vazifekhah S., et al. (2024). The effects of synbiotic supplementation on blood pressure and other maternal outcomes in pregnant mothers with mild preeclampsia: A triple-blinded randomized controlled trial. BMC Womens Health 24:80. DOI:10.1186/s12905-024-02922-6
Wan J., An L., Ren Z., et al. (2023). Effects of galactooligosaccharides on maternal gut microbiota, glucose metabolism, lipid metabolism and inflammation in pregnancy: A randomized controlled pilot study. Front. Endocrinol. 14:1034266. DOI:10.3389/fendo.2023.1034266
Phipps E. A., Thadhani R., Benzing T., et al. (2019). Pre-eclampsia: Pathogenesis, novel diagnostics and therapies. Nat. Rev. Nephrol. 15:275−289. DOI:10.1038/ s41581-019-0119-6
Qin X., Zhang M., Chen S., et al. (2024). Short-chain fatty acids in fetal development and metabolism. Trends Mol. Med. 31:625−639. DOI:10.1016/j.molmed.2024.11.014
Swingle K. L., Hamilton A. G., Safford H. C., et al. (2025). Placenta-tropic VEGF mRNA lipid nanoparticles ameliorate murine pre-eclampsia. Nature 637:412−421. DOI:10.1038/s41586-024-08291-2
Guo P., Wang W., Xiang Q., et al. (2024). Engineered probiotic ameliorates ulcerative colitis by restoring gut microbiota and redox homeostasis. Cell Host Microbe 32:1502. DOI:10.1016/j.chom.2024.07.028
Wang L., Liu Q., Chen Y., et al. (2022). Antioxidant potential of Pediococcus pentosaceus strains from the sow milk bacterial collection in weaned piglets. Microbiome 10:83. DOI:10.1186/s40168-022-01278-z
Stringer J. S. A., Pokaprakarn T., Prieto J. C., et al. (2024). Diagnostic accuracy of an integrated ai tool to estimate gestational age from blind ultrasound sweeps. JAMA 332:649−657. DOI:10.1001/jama.2024.10770
Bolatai A., He Y. and Wu N. (2022). Vascular endothelial growth factor and its receptors regulation in gestational diabetes mellitus and eclampsia. J. Transl. Med. 20:400. DOI:10.1186/s12967-022-03603-4
Zhang C. X. W., Candia A. A. and Sferruzzi-Perri A. N. (2024). Placental inflammation, oxidative stress, and fetal outcomes in maternal obesity. Trends Endocrin. Met. 35:638−647. DOI:10.1016/j.tem.2024.02.002
Sweeting A., Hannah W., Backman H., et al. (2024). Epidemiology and management of gestational diabetes. Lancet. 404:175−192. DOI:10.1016/S0140-6736(24)00825-0
Olmos-Ortiz A., Flores-Espinosa P., Díaz L., et al. (2021). Immunoendocrine dysregulation during gestational diabetes mellitus: The central role of the placenta. Int. J. Mol. Sci. 22:8087. DOI:10.3390/ijms22158087
Wang S., Cui Z. and Yang H. (2024). Interactions between host and gut microbiota in gestational diabetes mellitus and their impacts on offspring. BMC Microbiol. 24:161. DOI:10.1186/s12866-024-03255-y
Sun Z., Pan X.-F., Li X., et al. (2023). The gut microbiome dynamically associates with host glucose metabolism throughout pregnancy: Longitudinal findings from a matched case-control study of gestational diabetes mellitus. Adv. Sci. 10:e2205289. DOI:10.1002/advs.202205289
Wang S., Liu Y., Tam W. H., et al. (2024). Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring. Cell Host Microbe 32:1192−1206.e1195. DOI:10. 1016/j.chom.2024.06.005
Crusell M. K. W., Hansen T. H., Nielsen T., et al. (2018). Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum. Microbiome 6:89. DOI:10.1186/s40168-018-0472-x
Hu P., Chen X., Chu X., et al. (2021). Association of gut microbiota during early pregnancy with risk of incident gestational diabetes mellitus. J. Clin. Endocrin. Metab. 106:e4128−e4141. DOI:10.1210/clinem/dgab346
Pinto Y., Frishman S., Turjeman S., et al. (2023). Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis. Gut 72:918−928. DOI:10. 1136/gutjnl-2022-328406
Frishman S., Nuriel-Ohayon M., Turjeman S., et al. (2024). Positive effects of diet-induced microbiome modification on GDM in mice following human faecal transfer. Gut 73:e17. DOI:10.1136/gutjnl-2023-331456
Ye D., Huang J., Wu J., et al. (2023). Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans. Gut Microbes 15:2154552. DOI:10.1080/ 19490976.2022.2154552
Dimitriadis E., Rolnik D. L., Zhou W., et al. (2023). Pre-eclampsia. Nat. Rev. Dis. Primers 9:8. DOI:10.1038/s41572-023-00417-6
Paquin A., Werlang A. and Coutinho T. (2022). Arterial health abnormalities in women with pre-eclampsia: Contributing role of central obesity. Eur. Heart J. 43:ehac544.2502. DOI:10.1093/eurheartj/ehac544.2502
Ray J. G., Abdulaziz K. E., Berger H., et al. (2022). Aspirin use for preeclampsia prevention among women with prepregnancy diabetes, obesity, and hypertension. JAMA 327:388−390. DOI:10.1001/jama.2021.22749
Venkatesh S. S., Ferreira T., Benonisdottir S., et al. (2022). Obesity and risk of female reproductive conditions: A Mendelian randomisation study. PLoS Med 19:e1003679. DOI:10.1371/journal.pmed.1003679
Tyrmi J. S., Kaartokallio T., Lokki A. I., et al. (2023). Genetic risk factors associated with preeclampsia and hypertensive sisorders of pregnancy. JAMA Cardiol. 8:674−683. DOI:10.1001/jamacardio.2023.1312
Ahmadian E., Rahbar Saadat Y., Hosseiniyan Khatibi S. M., et al. (2020). Preeclampsia: Microbiota possibly playing a role. Pharmacol. Res. 155:104692. DOI:10. 1016/j.phrs.2020.104692
Colonetti T., Limas Carmo Teixeira D., Grande A. J., et al. (2023). The role of intestinal microbiota on pre-eclampsia: Systematic review and meta-analysis. Eur. J. Obstet. Gynecol. Reprod. Biol. 291:49−58. DOI:10.1016/j.ejogrb.2023.10.003
Liu X., Zeng X., Li X., et al. (2024). Landscapes of gut bacterial and fecal metabolic signatures and their relationship in severe preeclampsia. J. Transl. Med. 22:360. DOI:10.1186/s12967-024-05143-5
Chang Y., Chen Y., Zhou Q., et al. (2020). Short-chain fatty acids accompanying changes in the gut microbiome contribute to the development of hypertension in patients with preeclampsia. Clin. Sci. 134:289−302. DOI:10.1042/CS20191253
Hemberger M., Hanna C. W. and Dean W. (2020). Mechanisms of early placental development in mouse and humans. Nat. Rev. Gene 21:27−43. DOI:10.1038/s41576-019-0169-4
Meijer S., Pasquinelli E., Renzi S., et al. (2023). Gut micro- and mycobiota in preeclampsia: Bacterial composition differences suggest role in pathophysiology. Biomolecules 13:346. DOI:10.3390/biom13020346
Spencer R., Maksym K., Hecher K., et al. (2023). Maternal PlGF and umbilical Dopplers predict pregnancy outcomes at diagnosis of early-onset fetal growth restriction. J. Clin. Invest. 133:e169199. DOI:10.1172/JCI169199
Martins J. G., Biggio J. R. and Abuhamad A. (2020). Society for maternal-fetal medicine consult series #52: Diagnosis and management of fetal growth restriction: (replaces clinical guideline number 3, April 2012). Am. J. Obstet. Gynecol. 223:B2−B17. DOI:10.1016/j.ajog.2020.05.010
Lawn J. E., Ohuma E. O., Bradley E., et al. (2023). Small babies, big risks: Global estimates of prevalence and mortality for vulnerable newborns to accelerate change andimprovecounting.Lancet.401:1707−1719.DOI:10.1016/S0140-6736(23)00522-6
Conde-Agudelo A., Villar J., Risso M., et al. (2024). Metabolomic signatures associated with fetal growth restriction and small for gestational age: A systematic review. Nat. Commun. 15:9752. DOI:10.1038/s41467-024-53597-4
Garcia-Manau P., Bonacina E., Martin-Alonso R., et al. (2025). Angiogenic factors versus fetomaternal Doppler for fetal growth restriction at term: An open-label, randomized controlled trial. Nat. Med. 31:1008−1015. DOI:10.1038/s41591-024-03421-9
Arenas G. A. and Lorca R. A. (2024). Effects of hypoxia on uteroplacental and fetoplacental vascular function during pregnancy. Front. Physiol. 15:1490154. DOI:10.3389/fphys.2024.1490154
Hurtado I., Bonacina E., Garcia-Manau P., et al. (2023). Usefulness of angiogenic factors in prenatal counseling of late-onset fetal growth-restricted and small-for-gestational-age gestations: A prospective observational study. Arch. Gynecol. Obstet. 308:1485−1495. DOI:10.1007/s00404-022-06833-5
Carbillon L. (2024). Fetal growth decline may reflect placental dysfunction and high stillbirth risk in mothers with obesity. Am. J. Obstet. Gynecol. 230:101−102. DOI:10. 1016/j.ajog.2023.09.010
Gardosi J. and Hugh O. (2023). Stillbirth risk and smallness for gestational age according to Hadlock, INTERGROWTH-21st, WHO, and grow fetal weight standards: Analysis by maternal ethnicity and body mass index. Am. J. Obstet. Gynecol. MFM 229:547.e541−547.e513. DOI:10.1016/j.ajog.2023.05.026
Pritchard N. L., Hiscock R., Walker S. P., et al. (2023). Defining poor growth and stillbirth risk in pregnancy for infants of mothers with overweight and obesity. Am. J. Obstet. Gynecol. 229:59.e51−59.e12. DOI:10.1016/j.ajog.2022.12.322
Cömert T. K., Akpinar F., Erkaya S., et al. (2022). The effect of pre-pregnancy obesity on gut and meconium microbiome and relationship with fetal growth. J. Matern. Fetal Neona. 35:10629−10637. DOI:10.1080/14767058.2022.2148098
Tu X., Duan C., Lin B., et al. (2022). Characteristics of the gut microbiota in pregnant women with fetal growth restriction. BMC Pregnancy and Childb. 22:297. DOI:10. 1186/s12884-022-04635-w
Kosińska-Kaczyńska K., Krawczyk D., Bednorz M., et al. (2025). Maternal and placental microbiome and immune crosstalk in pregnancies with small-for-gestational-age fetuses-a pilot case-control study. Front. Cell Infect. Microbiol. 15:1596588. DOI:10.3389/fcimb.2025.1596588
He X., Li Z., Li X., et al. (2023). The fecal microbiota of gravidas with fetal growth restriction newborns characterized by metagenomic sequencing. Curr. Res. Transl. Med. 71:103354. DOI:10.1016/j.retram.2022.103354
Coskun R., Chang Z. L., Marcial Rodríguez A., et al. (2025). Effects of the gut microbiota on placental angiogenesis and intrauterine growth in gnotobiotic mice. Proc. Natl. Acad. Sci. USA 122:e2426341122. DOI. DOI:10.1073/pnas.2426341122
Ruebel M. L., Gilley S. P., Yeruva L., et al. (2024). Associations between maternal microbiome, metabolome and incidence of low-birth weight in Guatemalan participants from the Women First Trial. Front. Microbiol. 15:1456087. DOI:10.3389/ fmicb.2024.1456087
Ziętek M., Celewicz Z. and Szczuko M. (2021). Short-chain fatty acids, maternal microbiota and metabolism in pregnancy. Nutrients 13:1244. DOI:10.3390/ nu13041244
Wallace J. G., Bellissimo C. J., Yeo E., et al. (2019). Obesity during pregnancy results in maternal intestinal inflammation, placental hypoxia, and alters fetal glucose metabolism at mid-gestation. Sci. Rep. 9:17621. DOI:10.1038/s41598-019-54098-x
Koren O., Konnikova L., Brodin P., et al. (2024). The maternal gut microbiome in pregnancy: Implications for the developing immune system. Nat. Rev. Gastroenterol. Hepatol. 21:35−45. DOI:10.1038/s41575-023-00864-2
Enache R.-M., Profir M., Roşu O. A., et al. (2024). The role of gut microbiota in the onset and progression of obesity and associated comorbidities. Int. J. Mol. Sci. 25:12321. DOI:10.3390/ijms252212321
Stanislawski M. A., Dabelea D., Wagner B. D., et al. (2017). Pre-pregnancy weight, gestational weight gain, and the gut microbiota of mothers and their infants. Microbiome 5:113. DOI:10.1186/s40168-017-0332-0
Yang X., Zhang M., Zhang Y., et al. (2023). Ecological change of the gut microbiota during pregnancy and progression to dyslipidemia. npj Biofilms and Microbiomes 9:14. DOI:10.1038/s41522-023-00383-7
Sugino K. Y., Paneth N. and Comstock S. S. (2019). Michigan cohorts to determine associations of maternal pre-pregnancy body mass index with pregnancy and infant gastrointestinal microbial communities: Late pregnancy and early infancy. PLoS One 14:e0213733. DOI:10.1371/journal.pone.0213733
Abdullah B., Daud S., Aazmi M. S., et al. (2022). Gut microbiota in pregnant Malaysian women: A comparison between trimesters, body mass index and gestational diabetes status. BMC Pregnancy and Childb. 22:152. DOI:10.1186/ s12884-022-04472-x
Zacarías M. F., Collado M. C., Gómez-Gallego C., et al. (2018). Pregestational overweight and obesity are associated with differences in gut microbiota composition and systemic inflammation in the third trimester. PLoS One 13:e0200305. DOI:10.1371/journal.pone.0200305
Santacruz A., Collado M. C., García-Valdés L., et al. (2010). Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br. J. Nutr. 104:83−92. DOI:10.1017/ S0007114510000176
Yi D., Li T., Xiao Y., et al. (2025). Hydroxytyrosol improved insulin resistance in male offspring born to high-fat diet dams by remodeling gut microbiota. J. Nutr. Biochem. 146:110041. DOI:10.1016/j.jnutbio.2025.110041
Marousez L., Verce M., Dubernat L., et al. (2025). Maternal high-fat diet during lactation reduces sialylated milk oligosaccharides and shapes early-life microbiota in rat offspring. Food Funct. 16:5123−5132. DOI:10.1039/d5fo00559k
Gohir W., Kennedy K. M., Wallace J. G., et al. (2019). High-fat diet intake modulates maternal intestinal adaptations to pregnancy and results in placental hypoxia, as well as altered fetal gut barrier proteins and immune markers. J. Physiol. 597:3029−3051. DOI:10.1113/JP277353
Guo Y., Wang Z., Chen L., et al. (2018). Diet induced maternal obesity affects offspring gut microbiota and persists into young adulthood. Food Funct. 9:4317−4327. DOI:10.1039/c8fo00444g
Gomez-Arango L. F., Barrett H. L., McIntyre H. D., et al. (2016). Connections between the gut microbiome and metabolic hormones in early pregnancy in overweight and obese women. Diabetes 65:2214−2223. DOI:10.2337/db16-0278
Gomez-Arango L. F., Barrett H. L., McIntyre H. D., et al. (2016). Increased systolic and diastolic blood pressure is associated with altered gut microbiota composition and butyrate production in early pregnancy. Hypertension 68:974−981. DOI:10.1161/ HYPERTENSIONAHA.116.07910
Han H., Yi B., Zhong R., et al. (2021). From gut microbiota to host appetite: Gut microbiota-derived metabolites as key regulators. Microbiome 9:162. DOI:10.1186/ s40168-021-01093-y
Wu W., Lo Y., Chiu J., et al. (2024). Gut microbes with the GBU genes determine TMAO production from L-carnitine intake and serve as a biomarker for precision nutrition. Gut Microbes 17:2446374. DOI:10.1080/19490976.2024.2446374
York A. (2021). A muciniphila boosts metabolic health. Nat. Rev. Micro. 19:343−343. DOI:10.1038/s41579-021-00556-1
Yoon H. S., Cho C. H., Yun M. S., et al. (2021). Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat. Microbiol. 6:563−573. DOI:10.1038/ s41564-021-00880-5
Chanda D. and De D. (2024). Meta-analysis reveals obesity associated gut microbial alteration patterns and reproducible contributors of functional shift. Gut Microbes 16:2304900. DOI:10.1080/19490976.2024.2304900
Ziętek M., Celewicz Z., Kikut J., et al. (2021). Implications of SCFAs on the parameters of the lipid and hepatic profile in pregnant women. Nutrients 13:1749. DOI:10.3390/nu13061749
Molan K., Ambrožič Avguštin J., Likar M., et al. (2025). Fecal short-chain fatty acids are associated with obesity in gestational diabetes. Biomedicines 13:387. DOI:10. 3390/biomedicines13020387
Kim K. N., Yao Y. and Ju S. Y. (2019). Short chain fatty acids and fecal microbiota abundance in humans with obesity: A systematic review and meta-analysis. Nutrients 11:2512. DOI:10.3390/nu11102512
Mokkala K., Pellonperä O., Röytiö H., et al. (2017). Increased intestinal permeability, measured by serum zonulin, is associated with metabolic risk markers in overweight pregnant women. Metabolism 69:43−50. DOI:10.1016/j.metabol.2016.12. 015
Mishra S. P., Wang B., Jain S., et al. (2023). A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut. Gut 72:1848−1865. DOI:10.1136/gutjnl-2022-327365
Tang R., Xiao G., Jian Y., et al. (2022). The gut microbiota dysbiosis in preeclampsia contributed to trophoblast cell proliferation, invasion, and migration via lncRNA BC030099/NF-κB pathway. Mediators Inflamm. 2022:6367264. DOI:10.1155/2022/ 6367264
Feng H., Su R., Song Y., et al. (2016). Positive correlation between enhanced expression of TLR4/MyD88/NF-κB with insulin resistance in placentae of gestational diabetes mellitus. PLoS One 11:e0157185. DOI:10.1371/journal.pone. 0157185
Cheng S.-B., Nakashima A., Huber W. J., et al. (2019). Pyroptosis is a critical inflammatory pathway in the placenta from early onset preeclampsia and in human trophoblasts exposed to hypoxia and endoplasmic reticulum stressors. Cell Death Dis. 10:927. DOI:10.1038/s41419-019-2162-4
Fan M., Li X., Gao X., et al. (2019). LPS induces preeclampsia-like phenotype in rats and htr8/svneo cells dysfunction through TLR4/p38 MAPK pathway. Front. Physiol. 10:1030. DOI:10.3389/fphys.2019.01030
Wang J., Gu X., Yang J., et al. (2019). Gut microbiota dysbiosis and increased plasma LPS and TMAO levels in patients with preeclampsia. Front. Cell. Infect. Microbiol. 9:409. DOI:10.3389/fcimb.2019.00409
Li H., Liu S., Chen H., et al. (2024). Gut dysbiosis contributes to SCFAs reduction-associated adipose tissue macrophage polarization in gestational diabetes mellitus. Life Sci. 350:122744. DOI:10.1016/j.lfs.2024.122744
Tang H., Li H., Li D., et al. (2023). The gut microbiota of pregnant rats alleviates fetal growth restriction by inhibiting the TLR9/MyD88 pathway. J. Microbiol. Biotechnol. 33:1213−1227. DOI:10.4014/jmb.2304.04020
Yong W., Zhao Y., Jiang X., et al. (2022). Sodium butyrate alleviates pre-eclampsia in pregnant rats by improving the gut microbiota and short-chain fatty acid metabolites production. J. Appl. Microbiol. 132:1370−1383. DOI:10.1111/jam.15279
Tilves C., Yeh H., Maruthur N., et al. (2022). Increases in circulating and fecal butyrate are associated with reduced blood pressure and hypertension: Results from the SPIRIT trial. J. Am. Heart. Assoc. 11:e024763. DOI:10.1161/JAHA.121. 024763
Cui J., Wang J. and Wang Y. (2023). The role of short-chain fatty acids produced by gut microbiota in the regulation of pre-eclampsia onset. Front. Cell Infect. Microbiol. 13:1177768. DOI:10.3389/fcimb.2023.1177768
Kimura I., Miyamoto J., Ohue-Kitano R., et al. (2020). Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice. Science 367:eaaw8429. DOI:10.1126/science.aaw8429
Han W., Wang J., Yan X., et al. (2024). Butyrate and iso-butyrate: A new perspective on nutrition prevention of gestational diabetes mellitus. Nutrition & Diabetes 14:24. DOI:10.1038/s41387-024-00276-4
Grzeszczak K., Łanocha-Arendarczyk N., Malinowski W., et al. (2023). Oxidative stress in pregnancy. Biomolecules 13:1768. DOI:10.3390/biom13121768
Haidery F., Lambertini L., Tse I., et al. (2025). NRF2 deficiency leads to inadequate beta cell adaptation during pregnancy and gestational diabetes. Redox Biol. 81:103566. DOI:10.1016/j.redox.2025.103566
Shi L., Wang Z., Xiao J., et al. (2025). Folic acid alleviates hydrogen peroxide-induced oxidative stress in bovine placental trophoblast cells by regulating the NRF2/mTOR signaling pathway. Int. J. Mol. Sci. 26:2818. DOI:10.3390/ijms26062818
Xie G., Zhang Q., Dong J., et al. (2024). Maternal vitamin D3 supplementation in an oxidized-oil diet protects fetus from developmental impairment and ameliorates oxidative stress in mouse placenta and fetus. J. Nutr. 154:2920−2931. DOI:10.1016/j. tjnut.2024.07.025
Zakeri S., Rahimi Z., Rezvani N., et al. (2024). The influence of Nrf2 gene promoter methylation on gene expression and oxidative stress parameters in preeclampsia. BMC Med. Genomics 17:64. DOI:10.1186/s12920-023-01791-6
Yanagisawa M., Nagamatsu T., Kurano M., et al. (2023). Upregulation of autotaxin by oxidative stress via Nrf2 activation: A novel insight into the compensation mechanism in preeclamptic placenta. J. Reprod. Immunol. 160:104153. DOI:10. 1016/j.jri.2023.104153
Duan Y., Sun F., Que S., et al. (2018). Prepregnancy maternal diabetes combined with obesity impairs placental mitochondrial function involving Nrf2/ARE pathway and detrimentally alters metabolism of offspring. Obes. Res. Clin. Pract. 12:90−100. DOI:10.1016/j.orcp.2017.01.002
Shandilya S., Kumar S., Kumar Jha N., et al. (2022). Interplay of gut microbiota and oxidative stress: Perspective on neurodegeneration and neuroprotection. J. Adv. Res. 38:223−244. DOI:10.1016/j.jare.2021.09.005
Kim S. Y., Chae C. W., Lee H. J., et al. (2020). Sodium butyrate inhibits high cholesterol-induced neuronal amyloidogenesis by modulating NRF2 stabilization-mediated ROS levels: Involvement of NOX2 and SOD1. Cell Death Dis. 11:469. DOI:10.1038/s41419-020-2663-1
Zhang Y., Cheng Y., Liu J., et al. (2022). Tauroursodeoxycholic acid functions as a critical effector mediating insulin sensitization of metformin in obese mice. Redox Biol. 57:102481. DOI:10.1016/j.redox.2022.102481
Zhang D. D. (2025). Thirty years of NRF2: Advances and therapeutic challenges. Nat. Rev. Drug. Discov. 24:421−444. DOI:10.1038/s41573-025-01145-0
Pérez-Gutiérrez L. and Ferrara N. (2023). Biology and therapeutic targeting of vascular endothelial growth factor A. Nat. Rev. Mol. Cell Biol. 24:816−834. DOI:10. 1038/s41580-023-00631-w
Liu J., Quan L., Wang J., et al. (2025). Knockdown of VEGF-B improves HFD-induced insulin resistance by enhancing glucose uptake in vascular endothelial cells via the PI3K/Akt pathway. Int. J. Biol. Macromol. 285:138279. DOI:10.1016/j.ijbiomac.2024. 138279
Umapathy A., Chamley L. W. and James J. L. (2020). Reconciling the distinct roles of angiogenic/anti-angiogenic factors in the placenta and maternal circulation of normal and pathological pregnancies. Angiogenesis 23:105−117. DOI:10.1007/ s10456-019-09694-w
Biwer L. A., Lu Q., Ibarrola J., et al. (2023). Smooth muscle mineralocorticoid receptor promotes hypertension after preeclampsia. Circ. Res. 132:674−689. DOI:10. 1161/CIRCRESAHA.122.321228
Di Martino D. D., Soldavini C. M., Rossi G., et al. (2023). The sFlt-1/PlGF ratio in patients affected by gestational diabetes and SARS-CoV-2 Infection. Metabolites 13:54. DOI:10.3390/metabo13010054
Kinugawa M., Kumasawa K., Nemoto K., et al. (2025). Impact of parity and prepregnancy BMI on second-trimester sFlt-1 and PlGF levels in normotensive pregnancies. Hypertens Pregnancy 44:2534022. DOI:10.1080/10641955.2025. 2534022
Lim J. H., Kim Y., Kim M. Y., et al. (2024). Placental growth factor deficiency initiates obesity- and aging-associated metabolic syndrome. Metabolism 161:156002. DOI:10.1016/j.metabol.2024.156002
Lin X., Zhang Y., He X., et al. (2021). The choline metabolite TMAO inhibits netosis and promotes placental development in GDM of humans and mice. Diabetes 70:2250−2263. DOI:10.2337/db21-0188
Wen Y., Peng L., Xu R., et al. (2019). Maternal serum trimethylamine-N-oxide is significantly increased in cases with established preeclampsia. Pregnancy Hypertens 15:114−117. DOI:10.1016/j.preghy.2018.12.001
Zhou T., Heianza Y., Chen Y., et al. (2019). Circulating gut microbiota metabolite Trimethylamine N-Oxide (TMAO) and changes in bone density in response to weight loss diets: The POUNDS lost trial. Diabetes Care 42:1365−1371. DOI:10.2337/dc19-0134
Chang Q.-X., Chen X., Ming-Xin Y., et al. (2021). Trimethylamine N-oxide increases soluble fms-like tyrosine Kinase-1 in human placenta via NADPH oxidase dependent ROS accumulation. Placenta 103:134−140. DOI:10.1016/j.placenta.2020. 10.021
Zhou S., Xue J., Shan J., et al. (2022). Gut-flora-dependent metabolite trimethylamine-n-oxide promotes atherosclerosis-associated inflammation responses by indirect ros stimulation and signaling involving AMPK and SIRT1. Nutrients 14:3338. DOI:10.3390/nu14163338
Ma Y., Yang Y., Lv M., et al. (2022). 1,25(OH)2D3 alleviates LPS-induced preeclampsia-like rats impairment in the protective effect by TLR4/NF-kB pathway. Placenta 130:34−41. DOI:10.1016/j.placenta.2022.10.012
Albers R. E., Kaufman M. R., Natale B. V., et al. (2019). Trophoblast-specific expression of Hif-1α results in preeclampsia-Like symptoms and fetal growth restriction. Sci. Rep. 9:2742. DOI:10.1038/s41598-019-39426-5
Desoye G. and Carter A. M. (2022). Fetoplacental oxygen homeostasis in pregnancies with maternal diabetes mellitus and obesity. Nat. Rev. Endocrinol. 18:593−607. DOI:10.1038/s41574-022-00717-z
Bellissimo C. J., Ribeiro T. A., Yeo E., et al. (2025). Maternal high-fat, high-sucrose diet-induced excess adiposity is linked to placental hypoxia and disruption of fetoplacental immune homeostasis in late gestation. Biol. Reprod. 7:ioaf143. DOI:10. 1093/biolre/ioaf143
Adams D., Beckers K., Gomes V., et al. (2021). Abstract P224: Obesity is associated with hypoxia at the maternal-fetal interface in a mouse model of superimposed preeclampsia, BPH/5. Hypertension 78:AP224−AP224. DOI:10.1161/hyp.78.suppl_1. P224
Yuan X., Ruan W., Bobrow B., et al. (2023). Targeting hypoxia-inducible factors: Therapeutic opportunities and challenges. Nat. Rev. Drug Discov. 23:175−200. DOI:10.1038/s41573-023-00848-6
Deng F., Yin C., Luo C., et al. (2025). Lactobacillus reuteri-mediated dietary xylooligosaccharides enhance jejunal cell survival via suppression of oxygen-dependent apoptotic processes in a pig model. Imeta 4:e70080. DOI:10.1002/imt2. 70080
Xu J., Yang Y., Li X., et al. (2023). Pleiotropic activities of succinate: The interplay between gut microbiota and cardiovascular diseases. Imeta 2:e124. DOI:10.1002/ imt2.124
Wang X., Xu S., Zhou X., et al. (2021). Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk. Nat. Commun. 12:3428. DOI:10. 1038/s41467-021-23827-0
Huber-Ruano I., Calvo E., Mayneris-Perxachs J., et al. (2022). Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate. Microbiome 10:135. DOI:10.1186/s40168-022-01306-y
Serena C., Ceperuelo-Mallafré V., Keiran N., et al. (2018). Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota. ISME J. 12:1642−1657. DOI:10.1038/s41396-018-0068-2
de Goffau, M.C., Lager, S., Sovio, U., et al. (2019). Human placenta has no microbiome but can contain potential pathogens. Nature 572:329−334. DOI:10.1038 /s41586-019-1451-5
Gaccioli F., Stephens K., Sovio U., et al. (2023). Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and foetal pro-inflammatory cytokines in term infants. Nat. Microbiol. 8:2338−2348. DOI:10.1038/s41564-023-01528-2
Benny P. A., Al-Akwaa F. M., Dirkx C., et al. (2021). Placentas delivered by prepregnant obese women have reduced abundance and diversity in the microbiome. FASEB J. 35:e21524. DOI:10.1096/fj.202002184RR
Tanz L. J., Stuart J. J., Rimm E. B., et al. (2017). Abstract P314: Higher c-reactive protein levels among women with a history of hypertensive disorders of pregnancy. Circulation 135:AP314−AP314. DOI:10.1161/circ.135.suppl_1.p314
Ye C., Katagiri S., Miyasaka N., et al. (2020). The periodontopathic bacteria in placenta, saliva and subgingival plaque of threatened preterm labor and preterm low birth weight cases: A longitudinal study in Japanese pregnant women. Clin. Oral Investig. 24:4261−4270. DOI:10.1007/s00784-020-03287-4
Parhi L., Abed J., Shhadeh A., et al. (2022). Placental colonization by Fusobacterium nucleatum is mediated by binding of the Fap2 lectin to placentally displayed Gal-GalNAc. Cell Rep. 38:110537. DOI:10.1016/j.celrep.2022.110537
Stockham S., Stamford J. E., Roberts C. T., et al. (2015). Abnormal pregnancy outcomes in mice using an induced periodontitis model and the haematogenous migration of Fusobacterium nucleatum sub-species to the murine placenta. PLoS One 10:e0120050. DOI:10.1371/journal.pone.0120050
Wu C., Chen Y., Scheible M., et al. (2021). Genetic and molecular determinants of polymicrobial interactions in Fusobacterium nucleatum. Proc. Natl. Acad. Sci. USA 118:e2006482118. DOI:10.1073/pnas.2006482118
Kotzur R., Kahlon S., Isaacson B., et al. (2024). Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection. PLoS Pathog. 20:e1011923. DOI:10.1371/journal.ppat.1011923
Einenkel R., Ehrhardt J., Zygmunt M., et al. (2024). Less is more! Low amount of Fusobacterium nucleatum supports macrophage-mediated trophoblast functions in vitro. Front. Immunol. 15:1447190. DOI:10.3389/fimmu.2024.1447190
Zakis D. R., Paulissen E., Kornete L., et al. (2022). The evidence for placental microbiome and its composition in healthy pregnancies: A systematic review. J. Reprod. Immunol. 149:103455. DOI:10.1016/j.jri.2021.103455
Socha M. W., Malinowski B., Puk O., et al. (2021). The role of NF-κB in uterine spiral arteries remodeling, insight into the cornerstone of preeclampsia. Int. J. Mol. Sci. 22:704. DOI:10.3390/ijms22020704
Chen C., Yang Z. and Qiu Z. (2023). Bioinformatics prediction and experimental validation of the role of macrophage polarization and ferroptosis in gestational diabetes mellitus. J. Inflamm. Res. 16:6087−6105. DOI:10.2147/jir.S440826
Zheng X., Ma W., Wang Y., et al. (2023). Heat stress-induced fetal intrauterine growth restriction is associated with elevated LPS levels along the maternal intestine-placenta-fetus axis in pregnant mice. J. Agric. Food. Chem. 71:19592−19609. DOI:10.1021/acs.jafc.3c07058
Zhang H., Liu X., Zheng Y., et al. (2022). Effects of the maternal gut microbiome and gut-placental axis on melatonin efficacy in alleviating cadmium-induced fetal growth restriction. Ecotoxicol. Environ. Saf. 237:113550. DOI:10.1016/j.ecoenv.2022. 113550
Cotechini T., Komisarenko M., Sperou A., et al. (2014). Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia. J. Exp. Med. 211:165−179. DOI:10.1084/jem.20130295
Jahan F., Vasam G., Cariaco Y., et al. (2023). A comparison of rat models that best mimic immune-driven preeclampsia in humans. Front. Endocr. 14:1219205. DOI:10. 3389/fendo.2023.1219205
Fricke E. M., Elgin T. G., Gong H., et al. (2018). Lipopolysaccharide-induced maternal inflammation induces direct placental injury without alteration in placental blood flow and induces a secondary fetal intestinal injury that persists into adulthood. Am. J. Reprod. Immunol. 79:e12816. DOI:10.1111/aji.12816
Deer E., Herrock O., Campbell N., et al. (2023). The role of immune cells and mediators in preeclampsia. Nat. Rev. Nephrol. 19:257−270. DOI:10.1038/s41581-022-00670-0
Joshi N. P., Madiwale S. D., Sundrani D. P., et al. (2023). Fatty acids, inflammation and angiogenesis in women with gestational diabetes mellitus. Biochimie 212:31−40. DOI:10.1016/j.biochi.2023.04.005
Al-Ofi E., Alrafiah A., Maidi S., et al. (2021). Altered expression of angiogenic biomarkers in pregnancy associated with gestational diabetes. Int. J. Gen. Med. 14:3367−3375. DOI:10.2147/IJGM.S316670
Villota S. D., Toledo-Rodriguez M. and Leach L. (2021). Compromised barrier integrity of human feto-placental vessels from gestational diabetic pregnancies is related to downregulation of occludin expression. Diabetologia 64:195−210. DOI:10. 1007/s00125-020-05290-6
Musa E., Salazar-Petres E., Arowolo A., et al. (2023). Obesity and gestational diabetes independently and collectively induce specific effects on placental structure, inflammation and endocrine function in a cohort of South African women. J. Physiol. 601:1287−1306. DOI:10.1113/JP284139
Chen D., Wang Y., Li S., et al. (2022). Maternal propionate supplementation ameliorates glucose and lipid metabolic disturbance in hypoxia-induced fetal growth restriction. Food Funct. 13:10724−10736. DOI:10.1039/d2fo01481e
Guo H., Yang Y., Qiao Y., et al. (2021). Heat stress affects fetal brain and intestinal function associated with the alterations of placental barrier in late pregnant mouse. Ecotoxicol. Environ. Saf. 227:112916. DOI:10.1016/j.ecoenv.2021.112916
Sun P., Wang M., Chai X., et al. (2025). Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice. Nat. Commun. 16:2105. DOI:10.1038/s41467-025-57414-4
Sun P., Wang M., Liu Y., et al. (2023). High-fat diet-disturbed gut microbiota-colonocyte interactions contribute to dysregulating peripheral tryptophan-kynurenine metabolism. Microbiome 11:154. DOI:10.1186/s40168-023-01606-x
Pessa-Morikawa T., Husso A., Kärkkäinen O., et al. (2022). Maternal microbiota-derived metabolic profile in fetal murine intestine, brain and placenta. BMC Microbiol. 22:46. DOI:10.1186/s12866-022-02457-6
Peng X., Huang Y., Wang G., et al. (2022). Maternal long-term intake of inulin improves fetal development through gut microbiota and related metabolites in a rat model. J. Agric. Food Chem. 70:1840−1851. DOI:10.1021/acs.jafc.1c07284
Perry A., Stephanou A. and Rayman M. P. (2022). Dietary factors that affect the risk of pre-eclampsia. BMJ Nutr. Prev. Health. 5:118−133. DOI:10.1136/bmjnph-2021-000399
Hart T. L., Petersen K. S. and Kris-Etherton P. M. (2022). Nutrition recommendations for a healthy pregnancy and lactation in women with overweight and obesity – strategies for weight loss before and after pregnancy. Fertil. and Steril. 118:434−446. DOI:10.1016/j.fertnstert.2022.07.027
Yu E. W., Gao L., Stastka P., et al. (2020). Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial. PLoS Med. 17:e1003051. DOI:10.1371/journal.pmed.1003051
Tao Y., Gu Y., Mao X., et al. (2020). Effects of probiotics on type II diabetes mellitus: A meta-analysis. J. Transl. Med. 18:30. DOI:10.1186/s12967-020-02213-2
Halkjær S. I., Refslund Danielsen M., de Knegt V. E., et al. (2024). Multi-strain probiotics during pregnancy in women with obesity influence infant gut microbiome development: Results from a randomized, double-blind placebo-controlled study. Gut Microbes 16:2337968. DOI:10.1080/19490976.2024.2337968
Jones J. M., Reinke S. N., Mousavi-Derazmahalleh M., et al. (2024). Maternal prebiotic supplementation during pregnancy and lactation modifies the microbiome and short chain fatty acid profile of both mother and infant. Clin. Nutr. 43:969−980. DOI:10.1016/j.clnu.2024.02.030
Halkjær S. I., de Knegt V. E., Kallemose T., et al. (2023). No effect of multi-strain probiotic supplementation on metabolic and inflammatory markers and newborn body composition in pregnant women with obesity: Results from a randomized, double-blind placebo-controlled study. Nutr. Metab. Cardiovasc. Dis. 33:2444−2454. DOI:10.1016/j.numecd.2023.07.030
Halkjær S. I., de Knegt V. E., Lo B., et al. (2020). Multistrain probiotic increases the gut microbiota diversity in obese pregnant women: Results from a randomized, double-blind placebo-controlled study. Curr. Dev. Nutr. 4:nzaa095. DOI:10.1093/cdn /nzaa095
Okesene-Gafa K. A. M., Li M., McKinlay C. J. D., et al. (2019). Effect of antenatal dietary interventions in maternal obesity on pregnancy weight-gain and birthweight: Healthy mums and babies (HUMBA) randomized trial. Am. J. Obstet. Gynecol. 221:152.e151−152.e113. DOI:10.1016/j.ajog.2019.03.003
Lindsay K. L., Kennelly M., Culliton M., et al. (2014). Probiotics in obese pregnancy do not reduce maternal fasting glucose: A double-blind, placebo-controlled, randomized trial (Probiotics in Pregnancy Study). Am. J. Clin. Nutr. 99:1432−1439. DOI:10.3945/ajcn.113.079723
Saros L., Vahlberg T., Koivuniemi E., et al. (2022). Fish oil and/or probiotics intervention in overweight/obese pregnant women and overweight risk in 24-month-old children. J. Pediatr. Gastroenterol. Nutr. 76:218−226. DOI:10.1097/MPG. 0000000000003659
Fu Y., Gou W., Wu P., et al. (2024). Landscape of the gut mycobiome dynamics during pregnancy and its relationship with host metabolism and pregnancy health. Gut 73:1302−1312. DOI:10.1136/gutjnl-2024-332260
Hasain Z., Raja Ali R. A., Ahmad H. F., et al. (2022). The roles of probiotics in the gut microbiota composition and metabolic outcomes in asymptomatic post-gestational diabetes women: A randomized controlled trial. Nutrients 14:3878. DOI:10.3390/ nu14183878
Chatzakis C., Goulis D. G., Mareti E., et al. (2019). Prevention of gestational diabetes mellitus in overweight or obese pregnant women: A network meta-analysis. Diabetes Res. Clin. Pract. 158:107924. DOI:10.1016/j.diabres.2019.107924
Wang C., Tung Y., Chang H., et al. (2020). Effect of probiotic supplementation on newborn birth weight for mother with gestational diabetes mellitus or overweight/obesity: A systematic review and meta-analysis. Nutrients 12:3477. DOI:10.3390/nu12113477
Grev J., Berg M. and Soll R. (2018). Maternal probiotic supplementation for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst. Rev. 12:CD012519. DOI:10.1002/14651858.CD012519.pub2
Mantaring J., Benyacoub J., Destura R., et al. (2018). Effect of maternal supplement beverage with and without probiotics during pregnancy and lactation on maternal and infant health: A randomized controlled trial in the Philippines. BMC Pregnancy and Childb. 18:193. DOI:10.1186/s12884-018-1828-8
Hemberger M. and Dean W. (2023). The placenta: Epigenetic insights into trophoblast developmental models of a generation-bridging organ with long-lasting impact on lifelong health. Physiol. Rev. 103:2523−2560. DOI:10.1152/physrev.00001. 2023
Han X., Cai C., Deng W., et al. (2024). Landscape of human organoids: Ideal model in clinics and research. The Innovation 5:100620. DOI:10.1016/j.xinn.2024.100620
Itsuma N., Nakazawa M. and Yoko M. A. (2024). 3D morphogenesis and bacterial co-culture in a canine gut-on-a-chip using biopsy-derived intestinal organoids from healthy and ibd patients. Gastroenterology 30:S85. DOI:10.1053/j.gastro.2023.11. 271
Montgomery-Csobán T., Kavanagh K., Murray P., et al. (2024). Machine learning-enabled maternal risk assessment for women with pre-eclampsia (the PIERS-ML model): A modelling study. Lancet Digit. Health 6:e238−e250. DOI:10.1016/S2589-7500(23)00267-4
Wang L., Jia Z., Xu K., et al. (2024). When will dual-purpose pigs fly. The Innovation 5:100702. DOI:10.1016/j.xinn.2024.100702
Wild R. A., Zhao D., McPhaul M. J., et al. (2025). Weight loss before conception: Effects on atherogenic apolipoprotein lipid particles and endothelial function during pregnancy. F&S Reports 6:185−192. DOI:10.1016/j.xfre.2025.02.009
Hinkle S. N., Mumford S. L., Grantz K. L., et al. (2023). Gestational weight change in a diverse pregnancy cohort and mortality over 50 years: A prospective observational cohort study. Lancet. 402:1857−1865. DOI:10.1016/s0140-6736(23)01517-9
Perumal N., Wang D., Darling A. M., et al. (2023). Suboptimal gestational weight gain and neonatal outcomes in low and middle income countries: Individual participant data meta-analysis. BMJ 382:e072249. DOI:10.1136/bmj-2022-072249
Kasahara K., Ichikawa Y., Hironaka J., et al. (2025). Time for a change? Threshold for obesity in contemporary Japanese population. Metabolism 171:156352. DOI:10. 1016/j.metabol.2025.156352
Sun X., Sun Z., Peng W., et al. (2024). Expert consensus and call on actions for weight management in China: Advancing healthy China initiative through strategic actions. China CDC Weekly 6:1347−1353. DOI:10.46234/ccdcw2024.268
Hillesund E. R., Seland S., Bere E., et al. (2018). Preeclampsia and gestational weight gain in the Norwegian Fit for Delivery trial. BMC Res. Notes 11:282. DOI:10.1186/ s13104-018-3396-4
Catalano P. M. (2019). Reassessing strategies to improve pregnancy outcomes in overweight and obese women. Lancet Diabetes Endocrinol. 7:2−3. DOI:10.1016/ S2213-8587(18)30337-1
Houttu N., Vahlberg T., Miles E. A., et al. (2023). The impact of fish oil and/or probiotics on serum fatty acids and the interaction with low-grade inflammation in pregnant women with overweight and obesity: Secondary analysis of a randomised controlled trial. Br. J. Nutr. 131:1−16. DOI:10.1017/S0007114523001915
Chen Y., Li Z., Tye K. D., et al. (2019). Probiotic supplementation during human pregnancy affects the gut microbiota and immune status. Front. Cell Infect. Microbiol. 9:254. DOI:10.3389/fcimb.2019.00254
Obuchowska A., Gorczyca K., Standyło A., et al. (2022). Effects of probiotic supplementation during pregnancy on the future maternal risk of metabolic syndrome. Int. J. Mol. Sci. 23:8253. DOI:10.3390/ijms23158253
Gao S. and Wang J. (2023). Maternal and infant microbiome: Next-generation indicators and targets for intergenerational health and nutrition care. Protein Cell 14:807−823. DOI:10.1093/procel/pwad029
Cani P. D., Depommier C., Derrien M., et al. (2022). Akkermansia muciniphila: Paradigm for next-generation beneficial microorganisms. Nat. Rev. Gastroenterol Hepatol. 19:625−637. DOI:10.1038/s41575-022-00631-9
Altemani F., Barrett H. L., Gomez-Arango L., et al. (2021). Pregnant women who develop preeclampsia have lower abundance of the butyrate-producer Coprococcus in their gut microbiota. Pregnancy Hypertens 23:211−219. DOI:10.1016/j.preghy. 2021.01.002
Rasmussen T. S., Mentzel C. M. J., Danielsen M. R., et al. (2023). Fecal virome transfer improves proliferation of commensal gut Akkermansia muciniphila and unexpectedly enhances the fertility rate in laboratory mice. Gut Microbes 15:2208504. DOI:10.1080/19490976.2023.2208504
Qaisar R., Zuhra H., Karim A., et al. (2025). Butyrate improves handgrip strength and physical performance by reducing intestinal leak in post-menopausal women, a randomized controlled trial. Euro. J. Nutr. 64:141. DOI:10.1007/s00394-025-03656-3
H. Al Wattar B., Dodds J., Placzek A., et al. (2019). Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial. PLoS Med. 16:e1002857. DOI:10.1371/journal.pmed.1002857
Zhang D., Cheng D., Cao Y., et al. (2022). The effect of dietary fiber supplement on prevention of gestational diabetes mellitus in women with pre-pregnancy overweight/obesity: A randomized controlled trial. Front. Pharm. 13:922015. DOI:10. 3389/fphar.2022.922015
Harreiter J., Simmons D., Desoye G., et al. (2019). Nutritional lifestyle intervention in obese pregnant women, including lower carbohydrate intake, is associated with increased maternal free fatty acids, 3-β-hydroxybutyrate, and fasting glucose concentrations: A secondary factorial analysis of the european multicenter, randomized controlled DALI lifestyle intervention trial. Diabetes Care 42:1380−1389. DOI:10.2337/dc19-0418
Molina-Vega M., Picón-César M. J., Gutiérrez-Repiso C., et al. (2021). Metformin action over gut microbiota is related to weight and glycemic control in gestational diabetes mellitus: A randomized trial. Biomed. Pharmacother. 145:112465. DOI:10. 1016/j.biopha.2021.112465
Wu K., Zhang Y., Wang T., et al. (2025). Advancing disease-modifying therapies for Parkinson’s disease: Current strategies and future directions. The Innovation 101112. DOI:10.1016/j.xinn.2025.101112
Ratiner K., Ciocan D., Abdeen S. K., et al. (2024). Utilization of the microbiome in personalized medicine. Nat. Rev. Microbiol. 22:291−308. DOI:10.1038/s41579-023-00998-9
Carneiro P. V., Montenegro N. d. A., Lana A., et al. (2022). Lipids from gut microbiota: Pursuing a personalized treatment. Trends Mol Med 28:631−643. DOI:10.1016/j. molmed.2022.06.001
