# Microbiome, Epigenetics, and Nutritional Factors in Shaping Perinatal Pregnancy Outcomes

**Authors:** Miljana Z. Jovandaric, Sandra Babic, Milos Milincic, Biljana Medjo, Misela Raus, Mirjana Krstic, Dejan Tiric

PMC · DOI: 10.3390/ijms27041622 · International Journal of Molecular Sciences · 2026-02-07

## TL;DR

This paper explores how maternal nutrition, gut microbiome, and epigenetics influence pregnancy and neonatal outcomes.

## Contribution

The study integrates microbiome, epigenetics, and nutrition to reveal molecular networks affecting perinatal health.

## Key findings

- Maternal diet and microbiome metabolites influence placental function and fetal growth.
- Epigenetic and oxidative stress pathways are modulated by maternal nutritional and microbial factors.
- Targeted modulation of these networks can lead to personalized strategies for better neonatal outcomes.

## Abstract

Maternal nutrition and gut microbiome composition are central regulators of fetal development and perinatal outcomes, modulating immune signaling, oxidative balance, and epigenetic programming. The authors searched PubMed, Scopus, the Cochrane Library, and Web of Science for full-text, peer-reviewed articles published in English between 2010 and 2025, using keywords relevant to maternal diet, gut microbiome, epigenetic modifications, oxidative stress, reactive oxygen species (ROS), short-chain fatty acids (SCFAs), placental function, and perinatal outcomes. Selected studies provided detailed insights into how maternal dietary patterns and microbiome-derived metabolites influence placental function, fetal growth, and neonatal health. Integration of the microbiome, epigenetics, and nutritional factors reveals key molecular and metabolic networks that shape perinatal health. Targeted modulation of these networks provides a foundation for personalized strategies to improve neonatal outcomes.

## Full-text entities

- **Genes:** MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938] {aka HCN, LINC00047, NCRNA00047, NEAT2, PRO2853, miPEP-52}, LPL (lipoprotein lipase) [NCBI Gene 4023] {aka HDLCQ11, LIPD}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, DNMT3B (DNA methyltransferase 3 beta) [NCBI Gene 1789] {aka FSHD4, ICF, ICF1, M.HsaIIIB}, NPC1 (NPC intracellular cholesterol transporter 1) [NCBI Gene 4864] {aka NPC, POGZ, SLC65A1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, CPT1A (carnitine palmitoyltransferase 1A) [NCBI Gene 1374] {aka CPT I, CPT1, CPT1-L, CPTI-L, L-CPT1}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, H19 (H19 imprinted maternally expressed transcript) [NCBI Gene 283120] {aka ASM, ASM1, BWS, D11S813E, GMRSP, LINC00008}, FFAR3 (free fatty acid receptor 3) [NCBI Gene 2865] {aka FFA3R, GPR41}, AHR (aryl hydrocarbon receptor) [NCBI Gene 196] {aka FVH3, RP85, bHLHe76}, GPR166P (G protein-coupled receptor 166, pseudogene) [NCBI Gene 442206] {aka GPCR, PGR9}, VDR (vitamin D receptor) [NCBI Gene 7421] {aka NR1I1, PPP1R163}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, RXRA (retinoid X receptor alpha) [NCBI Gene 6256] {aka NR2B1, RXR-alpha, RXRalpha}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, ACACA (acetyl-CoA carboxylase alpha) [NCBI Gene 31] {aka ACAC, ACACAD, ACACalpha, ACC, ACC1, ACCA}, MIR146A (microRNA 146a) [NCBI Gene 406938] {aka MIRN146, MIRN146A, miR-146a, miRNA146A}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}, KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817] {aka INrf2, KLHL19}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MIR122 (microRNA 122) [NCBI Gene 406906] {aka MIR122A, MIRN122, MIRN122A, hsa-mir-122, miRNA122, miRNA122A}, NEAT1 (nuclear paraspeckle assembly transcript 1) [NCBI Gene 283131] {aka LINC00084, NCRNA00084, TP53LC15, TncRNA, VINC}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, CAT (catalase) [NCBI Gene 847], FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, FFAR2 (free fatty acid receptor 2) [NCBI Gene 2867] {aka FFA2R, GPR43}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, MEG3 (maternally expressed 3) [NCBI Gene 55384] {aka FP504, GTL2, LINC00023, Lnc-DLK1-35, NCRNA00023, PRO0518}
- **Diseases:** overweight (MESH:D050177), GDM (MESH:D016640), Obesity (MESH:D009765), nutritional deficits (MESH:D009748), mitochondrial distress (MESH:D012128), metabolic dysregulation (MESH:D021081), metabolic disorders (MESH:D008659), Endometriosis (MESH:D004715), trophoblastic dysfunction (MESH:D014328), bacterial vaginosis (MESH:D016585), hyperglycemia (MESH:D006943), atopic (MESH:C566404), metabolic syndrome (MESH:D024821), growth restriction (MESH:D005317), injury to (MESH:D014947), inflammation (MESH:D007249), periodontal infections (MESH:D010518), complications (MESH:D008107), preeclampsia (MESH:D011225), Dysbiosis (MESH:D064806), sexually transmitted infections (MESH:D012749), allergic, or metabolic disorders (MESH:D004342), pregnancy loss (MESH:D000022), necrotizing enterocolitis (MESH:D020345), maternal metabolic disorders (MESH:D000079262), immune dysregulation (OMIM:614878), chorioamnionitis (MESH:D002821), hypertensive disorders (MESH:D006973), PCOS (MESH:D011085), maternal malnutrition (MESH:D044342), birth (MESH:D000014), endotoxemia (MESH:D019446), placental insufficiency (MESH:D010927), insulin resistance (MESH:D007333), placental dysfunction (MESH:D010922), preterm birth (MESH:D047928), infection (MESH:D007239)
- **Chemicals:** S-adenosylmethionine (MESH:D012436), prostaglandin E2 (MESH:D015232), glycogen (MESH:D006003), iron (MESH:D007501), phenolic acids (MESH:C017616), arachidonic acid (MESH:D016718), acetyl-CoA (MESH:D000105), EPA (MESH:D015118), aldehydes (MESH:D000447), NO (MESH:D009569), cholesterol (MESH:D002784), Progesterone (MESH:D011374), inulin (MESH:D007444), resveratrol (MESH:D000077185), Essential amino acids (MESH:D000601), oxygen (MESH:D010100), Zinc (MESH:D015032), Dietary Fibers (MESH:D004043), Vitamin D (MESH:D014807), methionine (MESH:D008715), EGCG (MESH:C045651), essential fatty acid (MESH:D005228), triglyceride (MESH:D014280), simple sugars (MESH:D009005), choline (MESH:D002794), prostaglandin (MESH:D011453), cortisol (MESH:D006854), lactic acid (MESH:D019344), omega-3 (MESH:D015525), vitamin B12 (MESH:D014805), LPS (MESH:D008070), DHA (MESH:D004281), palmitic acid (MESH:D019308), resistant starch (MESH:D000084922), Lipids (MESH:D008055), glutathione (MESH:D005978), Prebiotics (MESH:D056692), peroxynitrite (MESH:D030421), glutamine (MESH:D005973), ATP (MESH:D000255), Polyphenols (MESH:D059808), SCFA (MESH:D005232), ROS (MESH:D017382), Folate (MESH:D005492), glucose (MESH:D005947), flavonoids (MESH:D005419), tryptophan (MESH:D014364), Acetate (MESH:D000085), sphingolipids (MESH:D013107), PUFAs (MESH:D005231), curcumin (MESH:D003474), bile acid (MESH:D001647), H2O2 (MESH:D006861), Compounds (-), Monounsaturated fatty acids (MESH:D005229), Carbohydrate (MESH:D002241), succinyl-CoA (MESH:C012046), Fatty Acids (MESH:D005227), Arginine (MESH:D001120), Selenium (MESH:D012643)
- **Species:** Pseudomonadota (proteobacteria, phylum) [taxon 1224], Veillonella (genus) [taxon 29465], Mus musculus (house mouse, species) [taxon 10090], Prevotella (genus) [taxon 838], Enterobacteriaceae (enterobacteria, family) [taxon 543], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Bacteroidia (class) [taxon 200643], Lactobacillus crispatus (species) [taxon 47770], gut metagenome (species) [taxon 749906], Lactobacillus gasseri (species) [taxon 1596], Streptococcus (genus) [taxon 1301], Bifidobacterium longum subsp. infantis (subspecies) [taxon 1682], Homo sapiens (human, species) [taxon 9606], Bacteroides (genus) [taxon 816], Fusobacterium (genus) [taxon 848], Staphylococcus (genus) [taxon 1279]

## Full text

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## Figures

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## References

174 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941002/full.md

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Source: https://tomesphere.com/paper/PMC12941002