Maternal selective serotonin reuptake inhibitor (SSRI) use is common during pregnancy and lactation. Changes in serotonin signaling may affect diversity and composition of microbes in the gut. Although research suggests SSRI drives microbial change, the extent to which the infant gut microbiome is affected is unknown. The infant gut microbiome is critical in early life for support of developmental health including early training of the immune system and metabolic programming. A total of N = 20 (10 SSRI, 10 control) maternal/infant dyads were enrolled in a pilot study. Thirty-six infant stool samples were collected at 1–2 and 4–6 weeks of life and sequenced using 16S rRNA sequencing. Investigative models included SSRI exposure as the primary variable of interest with infant feeding pattern and mode of delivery included as covariates. Maternal antidepressant use was not associated with infant alpha (within-sample) diversity. The SSRI use may shape beta (between-sample) diversity, particularly at weeks 4–6 of life (p = .072). Increases in the genera Gemella, Staphylococcus and Corynebacterium were observed with SSRI exposure. Additionally, results reveal a SSRI-associated decrease in Lactobacillus. While this pilot study is not intended to provide conclusive evidence, it is an important step in informing future research directions. Results suggest a modest influence of maternal SSRI exposure on the infant gut microbiome. Future studies should seek to use techniques like metagenomics, providing functional information to assess for local or systemic health impact and ultimately, clinical relevance.
AnanthanA.BalasubramanianH.RathC.MuthusamyS.RaoS.PatoleS. (2024). Lactobacillus rhamnosus GG as a probiotic for preterm infants: A strain specific systematic review and meta-analysis. European Journal of Clinical Nutrition, 78(10), 830–846. Springer Nature. https://doi.org/10.1038/s41430-024-01474-0
BäckhedF.RoswallJ.PengY.FengQ.JiaH.Kovatcheva-DatcharyP.LiY.XiaY.XieH.ZhongH.KhanM. T.ZhangJ.LiJ.XiaoL.Al-AamaJ.ZhangD.LeeY. S.KotowskaD.ColdingC.WangJ. (2015). Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host and Microbe, 17(5), 690–703. https://doi.org/10.1016/j.chom.2015.04.004
4.
BankoleT.LiY. (2025). The early-life gut microbiome in common pediatric diseases: Roles and therapeutic implications. In Frontiers in Nutrition (Vol. 12). Frontiers Media SA. https://doi.org/10.3389/fnut.2025.1597206
5.
BersethC. L.YeiserM.HarrisC. L.KinnamanJ. N.LappinV.WamplerJ. L.ZhuangW.VanderhoofJ. (2024). Infant formula with added Lacticaseibacillus rhamnosus GG supported adequate growth and was well tolerated in healthy term infants: A randomized controlled trial. Frontiers in Pediatrics, 12, 1456607. https://doi.org/10.3389/fped.2024.1456607
6.
BolyenE.RideoutJ. R.DillonM. R.BokulichN. A.AbnetC. C.Al-GhalithG. A.AlexanderH.AlmE. J.ArumugamM.AsnicarF.BaiY.BisanzJ. E.BittingerK.BrejnrodA.BrislawnC. J.BrownC. T.CallahanB. J.Caraballo-RodríguezA. M.ChaseJ.KnightR. (2019). Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nature Biotechnology, 37(8), 852–857. https://doi.org/10.1038/s41587-019-0209-9
7.
CallahanB. J.McMurdieP. J.RosenM. J.HanA. W.JohnsonA. J. A.HolmesS. P. (2016). DADA2: High-resolution sample inference from illumina amplicon data. Nature Methods, 13(7), 581–583. https://doi.org/10.1038/nmeth.3869
8.
ChakarounR. M.MassierL.KovacsP. (2020). Gut microbiome, intestinal permeability, and tissue bacteria in metabolic disease: Perpetrators or bystanders?Nutrients, 12(4), 1082. https://doi.org/10.3390/nu12041082
9.
Desorcy-SchererK.BendixenM. M.ParkerL. A. (2020). Determinants of the very low-birth-weight infant’s intestinal microbiome: A systematic review. Journal of Perinatal and Neonatal Nursing, 34(3), 257–275. https://doi.org/10.1097/JPN.0000000000000506
10.
Desorcy-SchererK.Zuniga-ChavesI.ReisnerM. A.SuenG.HernandezL. L. (2024). Investigating the influence of perinatal fluoxetine exposure on murine gut microbial communities during pregnancy and lactation. Scientific Reports, 14(1), 13762. https://doi.org/10.1038/s41598-024-62224-7
11.
EakleyR.LyndonA. (2022). Antidepressant use during pregnancy: Knowledge, attitudes, and decision-making of patients and providers. In Journal of midwifery and women’s health (Vol. 67, Issue 3, pp. 332–353). John Wiley and Sons Inc. https://doi.org/10.1111/jmwh.13366
12.
EnavH.BäckhedF.LeyR. E. (2022). The developing infant gut microbiome: A strain-level view. In Cell host and microbe (Vol. 30, Issue 5, pp. 627–638). Cell Press. https://doi.org/10.1016/j.chom.2022.04.009
13.
EwelsP.MagnussonM.LundinS.KällerM. (2016). MultiQC: Summarize analysis results for multiple tools and samples in a single report. Bioinformatics, 32(19), 3047–3048. https://doi.org/10.1093/bioinformatics/btw354
14.
FungT. C.VuongH. E.LunaC. D. G.PronovostG. N.AleksandrovaA. A.RileyN. G.VavilinaA.McGinnJ.RendonT.ForrestL. R.HsiaoE. Y. (2019). Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut. In Nature microbiology (Vol. 4, Issue 12, pp. 2064–2073). Nature Research. https://doi.org/10.1038/s41564-019-0540-4
15.
GalleyJ. D.Mashburn-WarrenL.BlalockL. C.LauberC. L.CarrollJ. E.RossK. M.HobelC.Coussons-ReadM.Dunkel SchetterC.GurT. L. (2023). Maternal anxiety, depression and stress affects offspring gut microbiome diversity and bifidobacterial abundances. Brain, Behavior, and Immunity, 107, 253–264. https://doi.org/10.1016/j.bbi.2022.10.005
16.
GaoM.TuH.LiuP.ZhangY.ZhangR.JingL.ZhangK. (2023). Association analysis of gut microbiota and efficacy of SSRIs antidepressants in patients with major depressive disorder. Journal of Affective Disorders, 330, 40–47. https://doi.org/10.1016/j.jad.2023.02.143
17.
GillmanM. W. (2005). Developmental origins of health and disease. New England Journal of Medicine, 353(17), 1848–1850. https://doi.org/10.1056/NEJMe058187
18.
GroerM. W.MillerE. M.D’AgataA.HoT. T. B.DutraS. V.YooJ. Y.YeeA. L.GilbertJ. A.DishawL. J. (2020). Contributors to dysbiosis in very-low-birth-weight infants. Journal of Obstetric, Gynecologic, and Neonatal Nursing, 49(3), 232–242. https://doi.org/10.1016/j.jogn.2020.02.003
19.
HeY.DuW.XiaoS.ZengB.SheX.LiuD.DuH.LiL.LiF.AiQ.HeJ.SongC.WeiH.ZhaoX.YuJ. (2021). Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells. Journal of Translational Medicine, 19(1), 510. https://doi.org/10.1186/s12967-021-03109-5
20.
HoskinsonC.DaiD. L. Y.Del BelK. L.BeckerA. B.MoraesT. J.MandhaneP. J.FinlayB. B.SimonsE.KozyrskyjA. L.AzadM. B.SubbaraoP.PetersenC.TurveyS. E. (2023). Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease. Nature Communications, 14(1), 4785. https://doi.org/10.1038/s41467-023-40336-4
21.
HutchisonS. M.MâsseL. C.PawluskiJ. L.OberlanderT. F. (2018). Perinatal selective serotonin reuptake inhibitor (SSRI) effects on body weight at birth and beyond: A review of animal and human studies. In Reproductive toxicology (Vol. 77, 109–121). Elsevier Inc. https://doi.org/10.1016/j.reprotox.2018.02.004
22.
JacksonM. A.VerdiS.MaxanM. E.ShinC. M.ZiererJ.BowyerR. C. E.MartinT.WilliamsF. M. K.MenniC.BellJ. T.SpectorT. D.StevesC. J. (2018). Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nature Communications, 9(1), 2655. https://doi.org/10.1038/s41467-018-05184-7
23.
JokelaR.PonseroA. J.DikarevaE.WeiX.KolhoK.-L.KorpelaK.De VosW. M.SalonenA. (2023). Sources of gut microbiota variation in a large longitudinal Finnish infant cohort. EBioMedicine, 94, 104695. https://doi.org/10.1016/j.ebiom.2023.104695
24.
KatohK.StandleyD. M. (2013). MAFFT multiple sequence alignment software version 7: Improvements in performance and usability. Molecular Biology and Evolution, 30(4), 772–780. https://doi.org/10.1093/molbev/mst010
25.
KersJ. G.SaccentiE. (2022). The power of microbiome studies: Some considerations on which alpha and beta metrics to use and how to report results. Frontiers in Microbiology, 12, 796025. https://doi.org/10.3389/fmicb.2021.796025
26.
KlindworthA.PruesseE.SchweerT.PepliesJ.QuastC.HornM.GlöcknerF. O. (2013). Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Research, 41(1), e1. https://doi.org/10.1093/nar/gks808
27.
KnollR. L.PodlesnyD.FortmannI.GöpelW.ZemlinM.LynchS.BorkP.GehringS.HärtelC. (2025). Staphylococcus aureus colonization and bloodstream infection in very preterm infants. Gut Microbes, 17(1), 2592423. https://doi.org/10.1080/19490976.2025.2592423
28.
KoopmanN.KatsavelisD.Ten HoveA. S.BrulS.de JongeW. J.SeppenJ. (2021). The multifaceted role of serotonin in intestinal homeostasis. In International journal of molecular sciences (Vol. 22, Issue 17, p. 9487). MDPI. https://doi.org/10.3390/ijms22179487
29.
LamireauN.GreinerE.HascoëtJ. M. (2023). Risk factors associated with necrotizing enterocolitis in preterm infants: A case–control study. Archives de Pediatrie, 30(7), 477–482. https://doi.org/10.1016/j.arcped.2023.07.003
30.
LinH.PeddadaS. D. (2024). Multigroup analysis of compositions of microbiomes with covariate adjustments and repeated measures. Nature Methods, 21(1), 83–91. https://doi.org/10.1038/s41592-023-02092-7
31.
MaiV.TorrazzaR. M.UkhanovaM.WangX.SunY.LiN.ShusterJ.SharmaR.HudakM. L.NeuJ. (2013). Distortions in development of intestinal microbiota associated with late onset sepsis in preterm infants. PLoS One, 8(1), e52876. https://doi.org/10.1371/journal.pone.0052876
32.
McMurdieP. J.HolmesS. (2013). Phyloseq: An R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One, 8(4), e61217. https://doi.org/10.1371/journal.pone.0061217
33.
NeuJ.PammiM. (2018). Necrotizing enterocolitis: The intestinal microbiome, metabolome and inflammatory mediators. In Seminars in Fetal and Neonatal Medicine (Vol. 23, Issue 6, pp. 400–405). W.B. Saunders Ltd. https://doi.org/10.1016/j.siny.2018.08.001
34.
PetersenJ. M.EspositoD. B.WerlerM. M. (2021). Selective serotonin reuptake inhibitor use patterns among commercially insured US pregnancies (2005–2014). Archives of Women’s Mental Health, 24(1), 155–164. https://doi.org/10.1007/s00737-020-01027-x
35.
PoglianiL.BaldelliS.CattaneoD.PileriP.ClementiE.CetinI.ZuccottiG. (2019). Selective serotonin reuptake inhibitors’ passage into human milk of lactating women. Journal of Maternal-Fetal and Neonatal Medicine, 32(18), 3020–3025. https://doi.org/10.1080/14767058.2018.1455180
36.
RamsteijnA. S.JašarevićE.HouwingD. J.BaleT. L.OlivierJ. D. A. (2020). Antidepressant treatment with fluoxetine during pregnancy and lactation modulates the gut microbiome and metabolome in a rat model relevant to depression. Gut Microbes, 11(4), 735–753. https://doi.org/10.1080/19490976.2019.1705728
37.
ShenY.YangX.LiG.GaoJ.LiangY. (2021). The change of gut microbiota in MDD patients under SSRIs treatment. Scientific Reports, 11(1), 14918. https://doi.org/10.1038/s41598-021-94481-1
VenkatramanA.MorelliJ. J.SampathV. (2025). Guardian of the gut: Butyrate-regulated FUT2 protects against experimental NEC. In Pediatric research (Vol. 97, Issue(1), pp. 25–26). Springer Nature. https://doi.org/10.1038/s41390-024-03522-8
40.
VuongH. E.ColeyE. J. L.KazantsevM.CookeM. E.RendonT. K.ParamoJ.HsiaoE. Y. (2021). Interactions between maternal fluoxetine exposure, the maternal gut microbiome and fetal neurodevelopment in mice. Behavioural Brain Research, 410, 113353. https://doi.org/10.1016/j.bbr.2021.113353
41.
WingettS. W.AndrewsS. (2018). FastQ Screen: A tool for multi-genome mapping and quality control. F1000Research, 7, 1338.
42.
YamamotoA.MccormickM. C.BurrisH. H. (2015). Disparities in antidepressant use in pregnancy. Journal of Perinatology, 35(4), 246–251. https://doi.org/10.1038/jp.2014.197
43.
ZhangH.ZhangZ.LiaoY.ZhangW.TangD. (2022). The complex link and disease between the gut microbiome and the immune system in infants. In Frontiers in cellular and infection microbiology (Vol. 12, pp. 924119). Frontiers Media S.A. https://doi.org/10.3389/fcimb.2022.924119
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