# Epigenetic modifications of gut microbiota and their potential role in atherosclerosis **Authors:** Shuang Guo, Junlai Zhao, Rongrong Zhu, Zhi Fan, Shibiao Liu, Weiwei Wu PMC · DOI: 10.3389/fphar.2025.1638240 · Frontiers in Pharmacology · 2025-07-16 ## TL;DR This paper reviews how gut microbes might influence atherosclerosis through epigenetic changes in gene activity. ## Contribution The paper systematically summarizes microbiota-driven epigenetic pathways and their role in atherosclerosis. ## Key findings - Gut microbiota influences atherosclerosis via DNA methylation and histone modifications. - Non-coding RNA networks mediate microbiota-epigenome interactions in plaque development. - Microbiota-epigenome crosstalk contributes to atherosclerotic processes. ## Abstract Emerging evidence positions the gut microbiota as a pivotal regulator of host metabolism and immunity, particularly in atherosclerosis pathogenesis, with epigenetic mechanisms serving as fundamental mediators of gene expression control. This review systematically summarizes gut microbiome-driven epigenetic pathways, encompassing DNA methylation, histone modifications, non-coding RNA networks and their interplay with atherosclerosis-related pathological processes. We synthesize current evidence on microbiota-epigenome crosstalk, highlighting its potential mechanistic contributions to atherosclerotic plaque development. ## Linked entities - **Diseases:** atherosclerosis (MONDO:0005311) ## Full-text entities - **Genes:** FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, EP300 (EP300 lysine acetyltransferase) [NCBI Gene 2033] {aka KAT3B, MKHK2, RSTS2, p300}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, MIR30C2 (microRNA 30c-2) [NCBI Gene 407032] {aka MIRN30C2, mir-30c-2}, CEBPA (CCAAT enhancer binding protein alpha) [NCBI Gene 1050] {aka C/EBP-alpha, CEBP}, TMPRSS11D (transmembrane serine protease 11D) [NCBI Gene 9407] {aka ASP, HAT}, ACSS1 (acyl-CoA synthetase short chain family member 1) [NCBI Gene 84532] {aka ACAS2L, ACECS1, AceCS2L}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, BRPF1 (bromodomain and PHD finger containing 1) [NCBI Gene 7862] {aka BR140, IDDDFP}, FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}, MIR20B (microRNA 20b) [NCBI Gene 574032] {aka MIRN20B, hsa-mir-20b, mir-20b}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, CXCL16 (C-X-C motif chemokine ligand 16) [NCBI Gene 58191] {aka CXCLG16, SR-PSOX, SRPSOX}, SLC16A1 (solute carrier family 16 member 1) [NCBI Gene 6566] {aka HHF7, MCT, MCT1, MCT1D}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3726] {aka AP-1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Hdac3 (histone deacetylase 3) [NCBI Gene 15183], PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, PNPLA2 (patatin like domain 2, triacylglycerol lipase) [NCBI Gene 57104] {aka 1110001C14Rik, ATGL, FP17548, PEDF-R, TTS-2.2, TTS2}, CREBBP (CREB binding lysine acetyltransferase) [NCBI Gene 1387] {aka CBP, KAT3A, MKHK1, RSTS, RSTS1}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, MIR663A (microRNA 663a) [NCBI Gene 724033] {aka MIR663, MIRN663, hsa-mir-663, hsa-mir-663a, mir-663a}, CDKN2B (cyclin dependent kinase inhibitor 2B) [NCBI Gene 1030] {aka CDK4I, INK4B, MTS2, P15, TP15, p15INK4b}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, Dnmt3a (DNA methyltransferase 3A) [NCBI Gene 13435] {aka MmuIIIA}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, HDAC1 (histone deacetylase 1) [NCBI Gene 3065] {aka GON-10, HD1, KDAC1, RPD3, RPD3L1}, ACSS2 (acyl-CoA synthetase short chain family member 2) [NCBI Gene 55902] {aka ACAS2, ACECS, ACS, ACSA, AceCS1, dJ1161H23.1}, Dnmt1 (DNA methyltransferase 1) [NCBI Gene 13433] {aka Cxxc9, Dnmt, Dnmt1o, MCMT, MTase, Met-1}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, ACACA (acetyl-CoA carboxylase alpha) [NCBI Gene 31] {aka ACAC, ACACAD, ACACalpha, ACC, ACC1, ACCA}, FFAR2 (free fatty acid receptor 2) [NCBI Gene 2867] {aka FFA2R, GPR43}, MIR106A (microRNA 106a) [NCBI Gene 406899] {aka MIRN106A, mir-106, mir-106a}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, KAT2A (lysine acetyltransferase 2A) [NCBI Gene 2648] {aka GCN5, GCN5L2, PCAF-b, hGCN5}, LPL (lipoprotein lipase) [NCBI Gene 4023] {aka HDLCQ11, LIPD}, UHRF1 (ubiquitin like with PHD and ring finger domains 1) [NCBI Gene 29128] {aka ICBP90, Np95, RNF106, TDRD22, hNP95, hUHRF1} - **Diseases:** peripheral artery disease (MESH:D058729), stunted colon development (MESH:D006130), calcification (MESH:D002114), hypertensive (MESH:D006973), myocardial infarctions (MESH:D009203), obese (MESH:D009765), type 2 diabetes (MESH:D003924), diabetes (MESH:D003920), AS (MESH:D050197), endothelial dysfunction (MESH:D014652), necrosis (MESH:D009336), hyperlipidemia (MESH:D006949), cardiovascular diseases (MESH:D002318), Deficiencies in folate (MESH:C562799), systemic (MESH:D015619), metabolic dysregulation (MESH:D021081), inflammation (MESH:D007249), vascular pathologies (MESH:D005598), metabolic disease (MESH:D008659), infections (MESH:D007239), insulin resistance (MESH:D007333), B12 (MESH:D014806), strokes (MESH:D020521), adiposity (MESH:D018205), cardiac anomalies (MESH:D006331), endotoxemia (MESH:D019446), atherosclerotic plaque (MESH:D058226) - **Chemicals:** Folate (MESH:D005492), acyl-CoA (MESH:D000214), catechins (MESH:D002392), curcumin (MESH:D003474), Propionate (MESH:D011422), isorhamnetin (MESH:C047368), fat (MESH:D005223), polydatin (MESH:C058229), Choline (MESH:D002794), 5 mC (-), NAD+ (MESH:D009243), cytosine (MESH:D003596), homocysteine (MESH:D006710), SCFAs (MESH:D005232), hydroxytyrosol (MESH:C005975), vitamin B6 (MESH:D025101), carnitine (MESH:D002331), Acetate (MESH:D000085), Butyrate (MESH:D002087), Q2 (MESH:C025204), B12 (MESH:C034730), lysine (MESH:D008239), lipid (MESH:D008055), LPS (MESH:D008070), phosphatidylcholine (MESH:D010713), 5-methylcytosine (MESH:D044503), Quercetin (MESH:D011794), Polyphenols (MESH:D059808), olive oil (MESH:D000069463), glycosides (MESH:D006027), TMA (MESH:C023336), propolis (MESH:D011429), resveratrol (MESH:D000077185), TMAO (MESH:C005855), fatty acid (MESH:D005227) - **Species:** gut metagenome (species) [taxon 749906], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Microbiota (genus) [taxon 13613], Mus musculus (house mouse, species) [taxon 10090], Faecalibacterium prausnitzii (species) [taxon 853] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12307311/full.md ## Figures 1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12307311/full.md ## References 49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12307311/full.md --- Source: https://tomesphere.com/paper/PMC12307311