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2000
Volume 25, Issue 4
  • ISSN: 1871-5249
  • E-ISSN: 1875-6166

Abstract

Background

More than 15% of women develop symptoms of depression during pregnancy, which often affects the mental and physical development of the newborn by altering its intestinal microbiota. Previous studies revealed that the gut microbiota plays a crucial role in the maturation of systems involved in the gut-brain axis, including the gastrointestinal system, the immune system, and the hypothalamic-pituitary-adrenal system axis.

Methods

This study aims to explore the cross-talk between the prenatal depression process and neonatal intestinal microbiota diversity. A total of 100 differentially expressed genes (DEGs) associated with prenatal depression were collected from various scientific publications and databases. Bioinformatics tools were used to analyze these DEGs. The STRING database. ToppGene database and DICE were employed for this integrative analysis.

Results

The network generated by the STRING database identified six pivotal genes: and . These genes regulate response to endogenous hormones, particularly cortisol secretion in newborns, as well as inhibiting serotonin secretion. Moreover, these genes are linked to major depressive disorder and other mental diseases, contributing to maternal and neonatal gut microbiota dysbiosis. Analysis using ToppGene and DICE’s further validated the biological processes identified by String, including the regulation of cellular cortisol secretion, metabolic processes, and serotonin inhibition.

Conclusion

The bioinformatics tools employed in this study allowed us to identify pivotal genes involved in prenatal depression, their associated signaling pathways, and their roles in modulating maternal and neonatal gut microbiota.

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2025-09-27

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References

  1. ChegdaniF. NouadiB. BennisF. Breastfeeding and the influence of the breast milk microbiota on infant health.Topics on Critical Issues in Neonatal Care.IntechOpen202210.5772/intechopen.99758
     [Google Scholar]
  2. ZijlmansM.A.C. KorpelaK. Riksen-WalravenJ.M. de VosW.M. de WeerthC. Maternal prenatal stress is associated with the infant intestinal microbiota.Psychoneuroendocrinology20155323324510.1016/j.psyneuen.2015.01.006 25638481
     [Google Scholar]
  3. AlamR. AbdolmalekyH.M. ZhouJ.R. Microbiome, inflammation, epigenetic alterations, and mental diseases.Am. J. Med. Genet. B. Neuropsychiatr. Genet.2017174665166010.1002/ajmg.b.32567 28691768
     [Google Scholar]
  4. RodriguezN. TunH.M. FieldC.J. MandhaneP.J. ScottJ.A. KozyrskyjA.L. Prenatal depression, breastfeeding, and infant gut microbiota.Front. Microbiol.20211266425710.3389/fmicb.2021.664257 34394021
     [Google Scholar]
  5. HuJ. LyJ. ZhangW. HuangY. GloverV. PeterI. HurdY.L. NomuraY. Microbiota of newborn meconium is associated with maternal anxiety experienced during pregnancy.Dev. Psychobiol.201961564064910.1002/dev.21837 30908632
     [Google Scholar]
  6. LitzkyJ.F. DeyssenrothM.A. EversonT.M. LesterB.M. LambertiniL. ChenJ. MarsitC.J. Prenatal exposure to maternal depression and anxiety on imprinted gene expression in placenta and infant neurodevelopment and growth.Pediatr. Res.20188351075108310.1038/pr.2018.27 29538358
     [Google Scholar]
  7. NemodaZ. SzyfM. Epigenetic alterations and prenatal maternal depression.Birth Defects Res.20171091288889710.1002/bdr2.1081 28714605
     [Google Scholar]
  8. AbrahamssonT.R. JakobssonH.E. AnderssonA.F. BjörksténB. EngstrandL. JenmalmM.C. Low diversity of the gut microbiota in infants with atopic eczema.J. Allergy Clin. Immunol.2012129243444010.1016/j.jaci.2011.10.025 22153774
     [Google Scholar]
  9. WilczyńskaP. SkarżyńskaE. Lisowska-MyjakB. Meconium microbiome as a new source of information about long-term health and disease: questions and answers.J. Matern. Fetal Neonatal Med.201932468168610.1080/14767058.2017.1387888 28969463
     [Google Scholar]
  10. SaadouneC. NouadiB. HamdaouiH. ChegdaniF. BennisF. Multiple myeloma: Bioinformatic analysis for identification of key genes and pathways.Bioinform. Biol. Insights2022161177932222111554510.1177/11779322221115545 35958298
     [Google Scholar]
  11. NouadiB. SbaouiY. El MessalM. BennisF. ChegdaniF. Integrative analysis of the genes induced by the intestine microbiota of infant born to term and breastfed.Bioinform. Biol. Insights20201410.1177/1177932220906168 32425510
     [Google Scholar]
  12. SbaouiY. NouadiB. EzaouineA. Rida SalamM. ElmessalM. BennisF. ChegdaniF. Functional prediction of biological profile during eutrophication in marine environment.Bioinform. Biol. Insights2022161177932221106399310.1177/11779322211063993 35023908
     [Google Scholar]
  13. ViuffA.C.F. PedersenL.H. KyngK. StaunstrupN.H. BørglumA. HenriksenT.B. Antidepressant medication during pregnancy and epigenetic changes in umbilical cord blood: A systematic review.Clin. Epigenetics2016819410.1186/s13148‑016‑0262‑x 27610205
     [Google Scholar]
  14. KatzE.R. StoweZ.N. NewportD.J. KelleyM.E. PaceT.W. CubellsJ.F. BinderE.B. Regulation of mRNA expression encoding chaperone and co-chaperone proteins of the glucocorticoid receptor in peripheral blood: Association with depressive symptoms during pregnancy.Psychol. Med.201242594395610.1017/S0033291711002121 21995950
     [Google Scholar]
  15. StillingR.M. DinanT.G. CryanJ.F. Microbial genes, brain & behaviour – epigeneticregulation of the gut – brain axis.Genes Brain Behav.201413698610.1111/gbb.12109
     [Google Scholar]
  16. LopizzoN. ZoncaV. CattaneN. ParianteC.M. CattaneoA. miRNAs in depression vulnerability and resilience: Novel targets for preventive strategies.J. Neural Transm. (Vienna)201912691241125810.1007/s00702‑019‑02048‑2 31350592
     [Google Scholar]
  17. BraithwaiteE.C. RamchandaniP.G. LaneT.A. MurphyS.E. Symptoms of prenatal depression are associated with raised salivary alpha-amylase levels.Psychoneuroendocrinology20156016317210.1016/j.psyneuen.2015.06.013 26150358
     [Google Scholar]
  18. SerpeloniF. RadtkeK.M. HeckerT. SillJ. VukojevicV. AssisS.G. SchauerM. ElbertT. NättD. Does prenatal stress shape postnatal resilience? – An epigenome-wide study on violence and mental health in humans.Front. Genet.20191026910.3389/fgene.2019.00269 31040859
     [Google Scholar]
  19. LiuY. MurphyS.K. MurthaA.P. FuemmelerB.F. SchildkrautJ. HuangZ. OvercashF. KurtzbergJ. JirtleR. IversenE.S. FormanM.R. HoyoC. Depression in pregnancy, infant birth weight and DNA methylation of imprint regulatory elements.Epigenetics20127773574610.4161/epi.20734 22677950
     [Google Scholar]
  20. AlbercaC.D. PapaleL.A. MadridA. GianatiempoO. CánepaE.T. AlischR.S. ChertoffM. Perinatal protein malnutrition results in genome-wide disruptions of 5-hydroxymethylcytosine at regions that can be restored to control levels by an enriched environment.Epigenetics202116101085110110.1080/15592294.2020.1841871 33172347
     [Google Scholar]
  21. SethS. LewisA. SafferyR. LappasM. GalballyM. Maternal prenatal mental health and placental 11β-HSD2 gene expression: Initial findings from the mercy pregnancy and emotional wellbeing study.Int. J. Mol. Sci.20151611274822749610.3390/ijms161126034 26593902
     [Google Scholar]
  22. OlivierJ.D.A. ÅkerudH. SkalkidouA. KaiholaH. Sundström-PoromaaI. The effects of antenatal depression and antidepressant treatment on placental gene expression.Front. Cell. Neurosci.2015846510.3389/fncel.2014.00465 25628539
     [Google Scholar]
  23. SchmidtM. BraunK. BrandweinC. RossettiA.C. Guara CiuranaS. RivaM.A. DeuschleM. BockJ. GassP. GrögerN. Maternal stress during pregnancy induces depressive-like behavior only in female offspring and correlates to their hippocampal Avp and Oxt receptor expression.Behav. Brain Res.201835311010.1016/j.bbr.2018.06.027 29958961
     [Google Scholar]
  24. HepgulN. CattaneoA. ZunszainP.A. ParianteC.M. Depression pathogenesis and treatment: What can we learn from blood mRNA expression?BMC Med.20131112810.1186/1741‑7015‑11‑28 23384232
     [Google Scholar]
  25. JanssenA.B. CapronL.E. O’DonnellK. TunsterS.J. RamchandaniP.G. HeazellA.E.P. GloverV. JohnR.M. Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3.Psychol. Med.201646142999301110.1017/S0033291716001598 27523184
     [Google Scholar]
  26. GustafssonH. SullivanE.L. NiggJ.T. LoftisJ.M. Maternal prenatal depression predicts infant negative affect via maternal inflammatory cytokine levels.Brain Behav. ImmunElsevier201766e1910.1016/j.bbi.2017.07.076 29920327
     [Google Scholar]
  27. Basta-KaimA. SzczesnyE. GlombikK. StachowiczK. SlusarczykJ. NalepaI.; Zelek- Molik, A.; Rafa- Zablocka, K.; Budziszewska, B.; Kubera, M.; Leskiewicz, M.; Lason, W. Prenatal stress affects insulin-like growth factor-1 (IGF-1) level and IGF-1 receptor phosphorylation in the brain of adult rats.Eur. Neuropsychopharmacol.20142491546155610.1016/j.euroneuro.2014.07.002 25106693
     [Google Scholar]
  28. SocałaK. DoboszewskaU. SzopaA. SerefkoA. WłodarczykM. ZielińskaA. PoleszakE. FichnaJ. WlaźP. The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders.Pharmacol. Res.202117210584010.1016/j.phrs.2021.105840 34450312
     [Google Scholar]
  29. RackersH.S. ThomasS. WilliamsonK. PoseyR. KimmelM.C. Emerging literature in the microbiota-brain axis and perinatal mood and anxiety disorders.Psychoneuroendocrinology201895869610.1016/j.psyneuen.2018.05.020 29807325
     [Google Scholar]
  30. AlonsoC. GuilarteM. VicarioM. RamosL. RezziS. MartínezC. LoboB. MartinF-P. PigrauM. González-CastroA.M. GallartM. MalageladaJ.R. AzpirozF. KochharS. SantosJ. Acute experimental stress evokes a differential gender-determined increase in human intestinal macromolecular permeability.Neurogastroenterol. MotilWiley Online Library201224(8)740e34910.1111/j.1365‑2982.2012.01928.x
     [Google Scholar]
  31. KarlJ.P. HatchA.M. ArcidiaconoS.M. PearceS.C. Pantoja-FelicianoI.G. DohertyL.A. SoaresJ.W. Effects of psychological, environmental and physical stressors on the gut microbiota.Front. Microbiol.20189201310.3389/fmicb.2018.02013 30258412
     [Google Scholar]
  32. VanuytselT. van WanrooyS. VanheelH. VanormelingenC. VerschuerenS. HoubenE. Salim RasoelS. TόthJ. HolvoetL. FarréR. Van OudenhoveL. BoeckxstaensG. VerbekeK. TackJ. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism.Gut20146381293129910.1136/gutjnl‑2013‑305690 24153250
     [Google Scholar]
  33. de PunderK. PruimboomL. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability.Front. Immunol.2015622310.3389/fimmu.2015.00223 26029209
     [Google Scholar]
  34. StillingR.M. DinanT.G. CryanJ.F. Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis.Genes Brain Behav.2014131698610.1111/gbb.12109 24286462
     [Google Scholar]
  35. GustafssonH.C. SullivanE.L. NousenE.K. SullivanC.A. HuangE. RinconM. NiggJ.T. LoftisJ.M. Maternal prenatal depression predicts infant negative affect via maternal inflammatory cytokine levels.Brain Behav. Immun.20187347048110.1016/j.bbi.2018.06.011 29920327
     [Google Scholar]
  36. VangeelE.B. IzziB. HompesT. VansteelandtK. LambrechtsD. FresonK. ClaesS. DNA methylation in imprinted genesIGF2 andGNASXL is associated with prenatal maternal stress.Genes Brain Behav.201514857358210.1111/gbb.12249 26333472
     [Google Scholar]
  37. HaraldB. GordonP. Meta-review of depressive subtyping models.J. Affect. Disord.2012139212614010.1016/j.jad.2011.07.015 21885128
     [Google Scholar]
  38. HughesE.R. WinterM.G. DuerkopB.A. SpigaL. Furtado de CarvalhoT. ZhuW. GillisC.C. BüttnerL. SmootM.P. BehrendtC.L. CherryS. SantosR.L. HooperL.V. WinterS.E. Microbial respiration and formate oxidation as metabolic signatures of inflammation-associated dysbiosis.Cell Host Microbe201721220821910.1016/j.chom.2017.01.005 28182951
     [Google Scholar]
  39. OberlanderT.F. WeinbergJ. PapsdorfM. GrunauR. MisriS. DevlinA.M. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses.Epigenetics2008329710610.4161/epi.3.2.6034 18536531
     [Google Scholar]
  40. BraithwaiteE.C. KundakovicM. RamchandaniP.G. MurphyS.E. ChampagneF.A. Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation.Epigenetics201510540841710.1080/15592294.2015.1039221 25875334
     [Google Scholar]
  41. BlakeleyP.M. CapronL.E. JensenA.B. O’DonnellK.J. GloverV. Maternal prenatal symptoms of depression and down regulation of placental monoamine oxidase A expression.J. Psychosom. Res.201375434134510.1016/j.jpsychores.2013.07.002 24119940
     [Google Scholar]
  42. NaoiM. MaruyamaW. Shamoto-NagaiM. Type A monoamine oxidase and serotonin are coordinately involved in depressive disorders: From neurotransmitter imbalance to impaired neurogenesis.J. Neural Transm. (Vienna)20181251536610.1007/s00702‑017‑1709‑8 28293733
     [Google Scholar]
  43. SunY. ZhangM. ChenC.C. GillillandM.III SunX. El-ZaatariM. HuffnagleG.B. YoungV.B. ZhangJ. HongS.C. ChangY.M. GumucioD.L. OwyangC. KaoJ.Y. Stress-induced corticotropin-releasing hormone-mediated NLRP6 inflammasome inhibition and transmissible enteritis in mice.Gastroenterology201314471478148710.1053/j.gastro.2013.02.038 23470617
     [Google Scholar]
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Integrative Analysis of the Impact of Prenatal Depression on the Newborn Intestinal Microbiota
Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Central Nervous System Agents) 25, 601 (2025); https://doi.org/10.2174/0118715249361952250209084153
/content/journals/cnsamc/10.2174/0118715249361952250209084153
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  • Article Type:     Research Article
Keyword(s): bioinformatics; DEGs; integrative analysis; intestinal microbiota; network; Prenatal depression

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