{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T16:58:09Z","timestamp":1793465889195,"version":"4.5.0"},"reference-count":205,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Postpartum depression (PPD) is a psychological disorder affecting approximately 10\u201315% of women following childbirth, with significant implications for maternal and infant well-being. While hormonal fluctuations and psychosocial factors have long been considered primary contributors, recent reports demonstrated that gut microbiome is implicated in modulating maternal mood and behavior. The bidirectional communication between the gut and brain, mediated by microbiota-gut-brain axis, along with genetic and epigenetic modifications, has gained increasing attention as a potential mechanistic pathway in PPD. However, the precise genetic and epigenetic underpinnings of this interaction remain to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This review aims to explore the genetic and epigenetic landscape of postpartum depression, with a significant focus pertinent to gut microbiota role in shaping neurobiological outcomes. By integrating recent findings from genomic, epigenomic, and microbiome research, we seek to elucidate novel mechanistic insights and potential therapeutic avenues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive literature search was conducted using public databases, including PubMed, Google Scholar, and NCBI, to identify relevant studies on PPD, gut microbiota, genetics, and epigenetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Gut microbiota and neuroimmune modulation: peripartum changes in gut microbiota composition have been linked to immune dysregulation, inflammation, and neurotransmitter imbalances, all of which are implicated in PPD pathophysiology. Genetics and epigenetics of PPD: Genome-wide association studies (GWAS) revealed a profound genetic risk loci associated with PPD. Additionally, DNA methylation, histone modifications, and non-coding RNAs have profound functional implications in gene expression regulation, influencing PPD susceptibility. Epigenetic influence of the gut microbiome: The gut microbiome affects epigenetic modifications, such as DNA methylation and histone acetylation, which may lead to fetal programming and maternal mental health disorders. Choline metabolism and maternal mental health: Choline, an essential nutrient involved in epigenetic regulation, influences gut microbiota composition and brain function. Dysregulation in choline metabolism is associated with higher risk of PPD. Clinical and therapeutic implications: Understanding the genetic and epigenetic mechanisms underlying PPD offers new avenues for personalized therapeutic interventions, including probiotic and prebiotic strategies, microbiome-based treatments, and targeted epigenetic therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The interplay between genetics, epigenetics, and gut microbiota represents a novel and promising area of research in understanding postpartum depression. The microbiota-gut-brain axis serves as a crucial mediator in this relationship, influencing neuroimmune regulation, neurotransmitter synthesis, and epigenetic modifications. Future studies should focus on integrating multi-omics approaches to unravel the molecular complexity of PPD and develop targeted interventions aimed at restoring microbiome and epigenetic homeostasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1778348","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T06:38:20Z","timestamp":1773988700000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The microbiota-gut-brain-epigenome axis as a novel therapeutic target for decoding postpartum depression"],"prefix":"10.3389","volume":"13","author":[{"given":"Boyuan","family":"Zheng","sequence":"first","affiliation":[{"name":"Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Encephalopathy, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanrong","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"332","DOI":"10.4088\/JCP.v62n0504","article-title":"Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study","volume":"62","author":"Ahokas","year":"2001","journal-title":"J Clin Psychiatry"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.3390\/cells13171436","article-title":"Gut-brain axis: role of microbiome, metabolomics, hormones, and stress in mental health disorders","volume":"13","author":"Verma","year":"2024","journal-title":"Cells"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12991-023-00469-8","article-title":"The role of gut microbiota in the pathogenesis and treatment of postpartum depression","volume":"22","author":"Zhang","year":"2023","journal-title":"Ann General Psychiatry"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/s41684-018-0129-1","article-title":"Is maternal microbial metabolism an early-life determinant of health?","volume":"47","author":"Romano","year":"2018","journal-title":"Lab Anim"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"243","DOI":"10.3389\/fgene.2015.00243","article-title":"Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy","volume":"6","author":"Bell","year":"2015","journal-title":"Front Genet"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.psyneuen.2016.04.008","article-title":"Oxytocin receptor DNA methylation in postpartum depression","volume":"69","author":"Kimmel","year":"2016","journal-title":"Psychoneuroendocrinology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.52586\/5006","article-title":"Co-expression modules construction by WGCNA and identify potential hub genes and regulation pathways of postpartum depression","volume":"26","author":"Deng","year":"2021","journal-title":"Front Biosci Landmark"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e101374","DOI":"10.1136\/gpsych-2023-101374","article-title":"Gut microbiota-derived short-chain fatty acids and depression: deep insight into biological mechanisms and potential applications","volume":"37","author":"Cheng","year":"2024","journal-title":"Gen Psychiatr"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"107029","DOI":"10.1016\/j.jff.2025.107029","article-title":"Decoding the gut-brain axis in depression: mechanistic insights and functional microbiota-based interventions","volume":"133","author":"Liu","year":"2025","journal-title":"J Funct Foods"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1415237","DOI":"10.3389\/fmicb.2024.1415237","article-title":"The causal association between gut microbiota and postpartum depression: a two-sample mendelian randomization study","volume":"15","author":"Jin","year":"2024","journal-title":"Front Microbiol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1099\/jmm.0.001112","article-title":"The gut microbiome and neuropsychiatric disorders: implications for attention deficit hyperactivity disorder (ADHD)","volume":"69","author":"Mathee","year":"2020","journal-title":"J Med Microbiol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1186\/s12888-025-07201-8","article-title":"The global burden of depression in adolescents and young adults, 1990\u20132021: systematic analysis of the global burden of disease study","volume":"25","author":"Liu","year":"2025","journal-title":"BMC Psychiatry"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/13651501.2026.2614011","article-title":"Global burden of anxiety disorders in adolescents and young adults aged 10\u201324 years from 1990 to 2021","volume":"8","author":"Tang","year":"2026","journal-title":"Int J Psychiatry Clin Pract"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1146\/annurev-clinpsy-072220-021440","article-title":"Major depression and its recurrences: life course matters","volume":"18","author":"Monroe","year":"2022","journal-title":"Annu Rev Clin Psychol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.3390\/pathogens11121540","article-title":"The history of the intestinal microbiota and the gut-brain axis","volume":"11","author":"Lewandowska-Pietruszka","year":"2022","journal-title":"Pathogens"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-020-1705-z","article-title":"The progress of gut microbiome research related to brain disorders","volume":"17","author":"Zhu","year":"2020","journal-title":"J Neuroinflammation"},{"key":"ref17","doi-asserted-by":"crossref","DOI":"10.1101\/2024.02.23.581833","article-title":"The lipidome of posttraumatic stress disorder","volume-title":"bioRxiv","author":"Bhargava","year":"2024"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"36967","DOI":"10.1007\/s11356-021-14593-z","article-title":"Microbiota\u2019s role in health and diseases","volume":"28","author":"El-Sayed","year":"2021","journal-title":"Environ Sci Pollut Res Int"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e38340","DOI":"10.7759\/cureus.38340","article-title":"Prevalence of depression in school-going adolescents and its impact on scholastic performance: a cross-sectional study","volume":"15","author":"Nirudya","year":"2023","journal-title":"Cureus"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"105840","DOI":"10.1016\/j.phrs.2021.105840","article-title":"The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders","volume":"172","author":"Soca\u0142a","year":"2021","journal-title":"Pharmacol Res"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/s12967-019-1971-7","article-title":"Smoking and microbiome in oral, airway, gut and some systemic diseases","volume":"17","author":"Huang","year":"2019","journal-title":"J Transl Med"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s40168-018-0531-3","article-title":"Influence of cigarette smoking on the human duodenal mucosa-associated microbiota","volume":"6","author":"Shanahan","year":"2018","journal-title":"Microbiome"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1111\/jgh.16199","article-title":"Alcohol, the gut microbiome, and liver disease","volume":"38","author":"Jew","year":"2023","journal-title":"J Gastroenterol Hepatol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3735","DOI":"10.3390\/ijms24043735","article-title":"Alcohol, inflammation, and microbiota in alcoholic liver disease","volume":"24","author":"Duki\u0107","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"725500","DOI":"10.3389\/fnins.2021.725500","article-title":"The gut microbiome and substance use disorder","volume":"15","author":"Russell","year":"2021","journal-title":"Front Neurosci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1097\/QAD.0000000000003363","article-title":"Multiomic analysis reveals microbiome-related relationships between cocaine use and metabolites","volume":"36","author":"Martinez","year":"2022","journal-title":"AIDS"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"100849","DOI":"10.1016\/j.yfrne.2020.100849","article-title":"Microbes and mental health: can the microbiome help explain clinical heterogeneity in psychiatry?","volume":"58","author":"Hayes","year":"2020","journal-title":"Front Neuroendocrinol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1007\/s12325-020-01272-7","article-title":"Current perspectives on gut microbiome dysbiosis and depression","volume":"37","author":"Capuco","year":"2020","journal-title":"Adv Ther"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/nature11234","article-title":"Structure, function and diversity of the healthy human microbiome","volume":"486","author":"Huttenhower","year":"2012","journal-title":"Nature"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/s41588-018-0135-7","article-title":"The fecal metabolome as a functional readout of the gut microbiome","volume":"50","author":"Zierer","year":"2018","journal-title":"Nat Genet"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"109129","DOI":"10.1016\/j.exer.2022.109129","article-title":"Expression and activation of the ketone body receptor HCAR2\/GPR109A promotes preservation of retinal endothelial cell barrier function","volume":"221","author":"Abdelrahman","year":"2022","journal-title":"Exp Eye Res"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.3390\/molecules28073213","article-title":"The role of probiotics and their metabolites in the treatment of depression","volume":"28","author":"Jach","year":"2023","journal-title":"Molecules"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s13668-020-00313-5","article-title":"Probiotics and the microbiota-gut-brain axis: focus on psychiatry","volume":"9","author":"M\u00f6rkl","year":"2020","journal-title":"Curr Nutr Rep"},{"key":"ref34","doi-asserted-by":"crossref","DOI":"10.1101\/2023.08.24.552964","article-title":"Regulation of lung immune tone by the gut-lung axis via dietary fiber, gut microbiota, and short-chain fatty acids","volume-title":"Biorxiv","author":"Maruyama","year":"2023"},{"key":"ref35","first-page":"417","article-title":"The maternal reward system in postpartum depression","volume-title":"Archives of women\u2019s mental health","author":"Post","year":"2019"},{"key":"ref36","first-page":"2975","article-title":"Adolescent stress impairs postpartum social behavior via anterior insula-prelimbic pathway in mice","volume-title":"Nature communications","author":"Kin","year":"2023"},{"key":"ref37","article-title":"Zuranolone Safety and Tolerability in Adults with Postpartum Depression: Analyses from SKYLARK, a 50 Mg Placebo-Controlled Study","author":"Samantha Meltzer-Brody","year":"2023"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"742236","DOI":"10.3389\/fendo.2021.742236","article-title":"The role of oxytocin and the effect of stress during childbirth: neurobiological basics and implications for mother and child","volume":"12","author":"Walter","year":"2021","journal-title":"Front Endocrinol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.psyneuen.2015.02.009","article-title":"Oxytocin and HPA stress axis reactivity in postpartum women","volume":"55","author":"Cox","year":"2015","journal-title":"Psychoneuroendocrinology"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.jad.2023.03.031","article-title":"DNA methylation in regulatory elements of the FKBP5 and NR3C1 gene in mother-child binomials with depression","volume":"331","author":"Mendon\u00e7a","year":"2023","journal-title":"J Affect Disord"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"112711","DOI":"10.1016\/j.psychres.2019.112711","article-title":"DNA methylation biomarkers prospectively predict both antenatal and postpartum depression","volume":"285","author":"Payne","year":"2020","journal-title":"Psychiatry Res"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/mp.2013.62","article-title":"Antenatal prediction of postpartum depression with blood DNA methylation biomarkers","volume":"19","author":"Guintivano","year":"2014","journal-title":"Mol Psychiatry"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1080\/15592294.2016.1146850","article-title":"Gestational stress induces depressive-like and anxiety-like phenotypes through epigenetic regulation of BDNF expression in offspring hippocampus","volume":"11","author":"Zheng","year":"2016","journal-title":"Epigenetics"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1016\/j.neurobiolaging.2014.12.035","article-title":"Longitudinal associations between BDNF promoter methylation and late-life depression","volume":"36","author":"Kang","year":"2015","journal-title":"Neurobiol Aging"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1080\/15592294.2015.1039221","article-title":"Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation","volume":"10","author":"Braithwaite","year":"2015","journal-title":"Epigenetics"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"3412","DOI":"10.1038\/s41598-025-86770-w","article-title":"Epigenetic modulation of social cognition: exploring the impact of methylation in brain-derived neurotrophic factor and oxytocin receptor genes across sex","volume":"15","author":"Park","year":"2025","journal-title":"Sci Rep"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1038\/npp.2015.333","article-title":"Replication of epigenetic postpartum depression biomarkers and variation with hormone levels","volume":"41","author":"Osborne","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"2252780","DOI":"10.1080\/19490976.2023.2252780","article-title":"Targeting microbial quorum sensing: the next frontier to hinder bacterial driven gastrointestinal infections","volume":"15","author":"Su","year":"2023","journal-title":"Gut Microbes"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpsychires.2015.02.021","article-title":"Collective unconscious: how gut microbes shape human behavior","volume":"63","author":"Dinan","year":"2015","journal-title":"J Psychiatr Res"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"2102878","DOI":"10.1080\/19490976.2022.2102878","article-title":"Microbiota-derived metabolites as drivers of gut\u2013brain communication","volume":"14","author":"Ahmed","year":"2022","journal-title":"Gut Microbes"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"611413","DOI":"10.3389\/fmicb.2021.611413","article-title":"Bacterial quorum-sensing systems and their role in intestinal bacteria-host crosstalk","volume":"12","author":"Wu","year":"2021","journal-title":"Front Microbiol"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1016\/j.tim.2021.04.006","article-title":"Vertical and horizontal quorum-sensing-based multicellular communications","volume":"29","author":"Wu","year":"2021","journal-title":"Trends Microbiol"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/s41579-019-0186-5","article-title":"Bacterial quorum sensing in complex and dynamically changing environments","volume":"17","author":"Mukherjee","year":"2019","journal-title":"Nat Rev Microbiol"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1016\/j.celrep.2015.02.049","article-title":"Manipulation of the quorum sensing signal AI-2 affects the antibiotic-treated gut microbiota","volume":"10","author":"Thompson","year":"2015","journal-title":"Cell Rep"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1023\/A:1007026504843","article-title":"Endothelial vesicles in the blood\u2013brain barrier: are they related to permeability?","volume":"20","author":"Stewart","year":"2000","journal-title":"Cell Mol Neurobiol"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1016\/j.cell.2015.10.067","article-title":"Establishment and dysfunction of the blood-brain barrier","volume":"163","author":"Zhao","year":"2015","journal-title":"Cell"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"126","DOI":"10.3389\/fnbeh.2019.00126","article-title":"Prophylactic effects of Bifidobacterium adolescentis on anxiety and depression-like phenotypes after chronic stress: a role of the gut microbiota-inflammation axis","volume":"13","author":"Guo","year":"2019","journal-title":"Front Behav Neurosci"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"647","DOI":"10.2147\/NDT.S159322","article-title":"Sex differences in gut microbiota in patients with major depressive disorder","volume":"14","author":"Chen","year":"2018","journal-title":"Neuropsychiatr Dis Treat"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.bbi.2015.03.016","article-title":"Altered fecal microbiota composition in patients with major depressive disorder","volume":"48","author":"Jiang","year":"2015","journal-title":"Brain Behav Immun"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.ebiom.2017.09.013","article-title":"Effect of Lactobacillus rhamnosus HN001 in pregnancy on postpartum symptoms of depression and anxiety: a randomised double-blind placebo-controlled trial","volume":"24","author":"Slykerman","year":"2017","journal-title":"EBioMedicine"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/mp.2016.44","article-title":"Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host\u2019s metabolism","volume":"21","author":"Zheng","year":"2016","journal-title":"Mol Psychiatry"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.jad.2016.09.051","article-title":"Prevotella and Klebsiella proportions in fecal microbial communities are potential characteristic parameters for patients with major depressive disorder","volume":"207","author":"Lin","year":"2017","journal-title":"J Affect Disord"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"1019578","DOI":"10.3389\/fgstr.2022.1019578","article-title":"Gut microbiota in anxiety and depression: pathogenesis and therapeutics","volume":"1","author":"Bibb\u00f2","year":"2022","journal-title":"Front Gastroenterol"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1093\/ije\/29.4.722","article-title":"An introduction to instrumental variables for epidemiologists","volume":"29","author":"Greenland","year":"2000","journal-title":"Int J Epidemiol"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1093\/aje\/kwu283","article-title":"Multivariable mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects","volume":"181","author":"Burgess","year":"2015","journal-title":"Am J Epidemiol"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1186\/s12916-022-02657-x","article-title":"Association between gut microbiota and preeclampsia-eclampsia: a two-sample mendelian randomization study","volume":"20","author":"Li","year":"2022","journal-title":"BMC Med"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1059281","DOI":"10.3389\/fmicb.2022.1059281","article-title":"Causal associations between gut microbiota and adverse pregnancy outcomes: a two-sample mendelian randomization study","volume":"13","author":"Li","year":"2022","journal-title":"Front Microbiol"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1093\/eurjpc\/zwad052","article-title":"Gut microbiome and risk of ischaemic stroke: a comprehensive mendelian randomization study","volume":"30","author":"Meng","year":"2023","journal-title":"Eur J Prev Cardiol"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1001\/jamapsychiatry.2022.4974","article-title":"Role of the gut-brain axis in the shared genetic etiology between gastrointestinal tract diseases and psychiatric disorders: a genome-wide pleiotropic analysis","volume":"80","author":"Gong","year":"2023","journal-title":"JAMA Psychiatry"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"694443","DOI":"10.3389\/fcimb.2021.694443","article-title":"919 syrup alleviates postpartum depression by modulating the structure and metabolism of gut microbes and affecting the function of the hippocampal GABA\/glutamate system","volume":"11","author":"Tian","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"e01899-01822","DOI":"10.1128\/spectrum.01899-22","article-title":"Alterations in the gut microbiota and metabolomics of seafarers after a six-month sea voyage","volume":"10","author":"Jiang","year":"2022","journal-title":"Microbiol Spectrum"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.jad.2022.08.012","article-title":"Gut microbiota and major depressive disorder: a bidirectional mendelian randomization","volume":"316","author":"Chen","year":"2022","journal-title":"J Affect Disord"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/MMBR.00019-15","article-title":"Taxonomy, physiology, and natural products of Actinobacteria","volume":"80","author":"Barka","year":"2016","journal-title":"Microbiol Mol Biol Rev"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1116065","DOI":"10.3389\/fnagi.2023.1116065","article-title":"Predictive microbial feature analysis in patients with depression after acute ischemic stroke","volume":"15","author":"Yao","year":"2023","journal-title":"Front Aging Neurosci"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s13041-021-00843-1","article-title":"Assessing the effect of interaction between C-reactive protein and gut microbiome on the risks of anxiety and depression","volume":"14","author":"Chen","year":"2021","journal-title":"Mol Brain"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1007\/s11682-022-00630-z","article-title":"Assessing the joint effects of brain aging and gut microbiota on the risks of psychiatric disorders","volume":"16","author":"Zhang","year":"2022","journal-title":"Brain Imaging Behav"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.biopsych.2010.03.018","article-title":"A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression","volume":"68","author":"Lin","year":"2010","journal-title":"Biol Psychiatry"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41588-020-00763-1","article-title":"Large-scale association analyses identify host factors influencing human gut microbiome composition","volume":"53","author":"Kurilshikov","year":"2021","journal-title":"Nat Genet"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"1282742","DOI":"10.3389\/fpsyt.2024.1282742","article-title":"Gut microbiota and postpartum depression: a mendelian randomization study","volume":"15","author":"Zhang","year":"2024","journal-title":"Front Psych"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/nrm.2017.135","article-title":"A user's guide to the ambiguous word'epigenetics","volume":"19","author":"Greally","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1101\/gad.1787609","article-title":"An operational definition of epigenetics","volume":"23","author":"Berger","year":"2009","journal-title":"Genes Dev"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1534\/genetics.109.102798","article-title":"Epigenetic inheritance and the missing heritability problem","volume":"182","author":"Slatkin","year":"2009","journal-title":"Genetics"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.neuron.2013.10.023","article-title":"The emerging field of neuroepigenetics","volume":"80","author":"Sweatt","year":"2013","journal-title":"Neuron"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/s41586-019-1411-0","article-title":"Advances in epigenetics link genetics to the environment and disease","volume":"571","author":"Cavalli","year":"2019","journal-title":"Nature"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.ebiom.2017.03.044","article-title":"Epigenetic pathways in human disease: the impact of DNA methylation on stress-related pathogenesis and current challenges in biomarker development","volume":"18","author":"Argentieri","year":"2017","journal-title":"EBioMedicine"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"4300","DOI":"10.1038\/s41380-020-00966-2","article-title":"Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males","volume":"26","author":"Yang","year":"2021","journal-title":"Mol Psychiatry"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"e156","DOI":"10.1002\/mco2.156","article-title":"The molecular pathophysiology of depression and the new therapeutics","volume":"3","author":"Tian","year":"2022","journal-title":"MedComm"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"e12423","DOI":"10.1111\/gbb.12423","article-title":"Epigenetics at the crossroads between genes, environment and resilience in anxiety disorders","volume":"17","author":"Schiele","year":"2018","journal-title":"Genes Brain Behav"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"e14739","DOI":"10.1371\/journal.pone.0014739","article-title":"Broad epigenetic signature of maternal care in the brain of adult rats","volume":"6","author":"McGowan","year":"2011","journal-title":"PLoS One"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.biopsych.2018.12.023","article-title":"Sensitive periods for the effect of childhood adversity on DNA methylation: results from a prospective, longitudinal study","volume":"85","author":"Dunn","year":"2019","journal-title":"Biol Psychiatry"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"a021741","DOI":"10.1101\/cshperspect.a021741","article-title":"The regulation of transcription in memory consolidation","volume":"7","author":"Alberini","year":"2015","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/S0092-8674(02)01074-7","article-title":"Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure","volume":"111","author":"Guan","year":"2002","journal-title":"Cell"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1056\/NEJMra073096","article-title":"Major depressive disorder","volume":"2","author":"Otte","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"ref94","doi-asserted-by":"crossref","DOI":"10.1515\/9780822391852","volume-title":"Depression: A Public Feeling","author":"Cvetkovich","year":"2020"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41586-018-0666-1","article-title":"m6A facilitates hippocampus-dependent learning and memory through YTHDF1","volume":"563","author":"Shi","year":"2018","journal-title":"Nature"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1016\/j.cell.2018.10.030","article-title":"Acetylation of cytidine in mRNA promotes translation efficiency","volume":"175","author":"Arango","year":"2018","journal-title":"Cell"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.brainresbull.2022.05.004","article-title":"Elevation of N-acetyltransferase 10 in hippocampal neurons mediates depression-and anxiety-like behaviors","volume":"185","author":"Guo","year":"2022","journal-title":"Brain Res Bull"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/s41392-023-01519-z","article-title":"Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential","volume":"8","author":"Yuan","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1530\/rep.1.00523","article-title":"Gene-nutrient interactions during fetal development","volume":"130","author":"Maloney","year":"2005","journal-title":"Reproduction"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1136\/bmj.301.6761.1111","article-title":"The fetal and infant origins of adult disease","volume":"301","author":"Barker","year":"1990","journal-title":"BMJ"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1136\/bmj.311.6998.171","article-title":"Fetal origins of coronary heart disease","volume":"311","author":"Barker","year":"1995","journal-title":"BMJ"},{"key":"ref102","first-page":"458","volume-title":"Mothers, Babies and Disease in Later Life","author":"Barker","year":"1998"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1257\/jep.25.3.153","article-title":"Killing me softly: the fetal origins hypothesis","volume":"25","author":"Almond","year":"2011","journal-title":"J Econ Perspect"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1146\/annurev.nutr.21.1.73","article-title":"The \u201cfetal origins\u201d hypothesis: challenges and opportunities for maternal and child nutrition","volume":"21","author":"Rasmussen","year":"2001","journal-title":"Annu Rev Nutr"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1073\/pnas.0610362104","article-title":"Childhood maltreatment predicts adult inflammation in a life-course study","volume":"104","author":"Danese","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.bbi.2012.08.010","article-title":"Do environments in infancy moderate the association between stress and inflammation in adulthood? Initial evidence from a birth cohort in the Philippines","volume":"31","author":"McDade","year":"2013","journal-title":"Brain Behav Immun"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1177\/0956797610370161","article-title":"Harsh family climate in early life presages the emergence of a proinflammatory phenotype in adolescence","volume":"21","author":"Miller","year":"2010","journal-title":"Psychol Sci"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.biopsych.2006.03.016","article-title":"Relationship of early life stress and psychological functioning to adult C-reactive protein in the coronary artery risk development in young adults study","volume":"60","author":"Taylor","year":"2006","journal-title":"Biol Psychiatry"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nrn3818","article-title":"Epigenetic and transgenerational reprogramming of brain development","volume":"16","author":"Bale","year":"2015","journal-title":"Nat Rev Neurosci"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/ng1089","article-title":"Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals","volume":"33","author":"Jaenisch","year":"2003","journal-title":"Nat Genet"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/nn.2514","article-title":"Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons","volume":"13","author":"Feng","year":"2010","journal-title":"Nat Neurosci"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/S0021-9258(18)57093-9","article-title":"A new synthesis of cytosine and 5-methylcytosine","volume":"177","author":"Hitchings","year":"1949","journal-title":"J Biol Chem"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1471-2091-6-6","article-title":"The de novo methylation activity of Dnmt3a is distinctly different than that of Dnmt1","volume":"6","author":"Hsieh","year":"2005","journal-title":"BMC Biochem"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1006\/bbrc.2001.6057","article-title":"Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1","volume":"289","author":"Kang","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/S0092-8674(00)81656-6","article-title":"DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development","volume":"99","author":"Okano","year":"1999","journal-title":"Cell"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1126\/science.1195380","article-title":"Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation","volume":"331","author":"Song","year":"2011","journal-title":"Science"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/166237b0","article-title":"Occurrence of 5-methyl-cytosine in nucleic acids","volume":"166","author":"Wyatt","year":"1950","journal-title":"Nature"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/j.1460-2075.1992.tb05055.x","article-title":"Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein","volume":"11","author":"Boyes","year":"1992","journal-title":"EMBO J"},{"key":"ref119","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.ccr.2014.07.028","article-title":"Gene body methylation can alter gene expression and is a therapeutic target in cancer","volume":"26","author":"Yang","year":"2014","journal-title":"Cancer Cell"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1126\/science.1063443","article-title":"Epigenetic reprogramming in mammalian development","volume":"293","author":"Reik","year":"2001","journal-title":"Science"},{"key":"ref121","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1111\/j.1753-4887.2008.00056.x","article-title":"The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome","volume":"66","author":"Dolinoy","year":"2008","journal-title":"Nutr Rev"},{"key":"ref122","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1186\/s13059-014-0522-z","article-title":"Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets","volume":"15","author":"Hall","year":"2014","journal-title":"Genome Biol"},{"key":"ref123","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1523\/JNEUROSCI.5372-11.2012","article-title":"Sex differences in the brain: the not so inconvenient truth","volume":"32","author":"McCarthy","year":"2012","journal-title":"J Neurosci"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s13148-015-0144-7","article-title":"Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases","volume":"7","author":"Paul","year":"2015","journal-title":"Clin Epigenetics"},{"key":"ref125","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1007\/s00018-009-0015-5","article-title":"DNA hypomethylation in the origin and pathogenesis of human diseases","volume":"66","author":"Pogribny","year":"2009","journal-title":"Cell Mol Life Sci"},{"key":"ref126","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.brainres.2008.07.077","article-title":"Epigenetic alterations in the brains of fisher 344 rats induced by long-term administration of folate\/methyl-deficient diet","volume":"1237","author":"Pogribny","year":"2008","journal-title":"Brain Res"},{"key":"ref127","first-page":"S1","article-title":"Vitamin and mineral intake is inadequate for most Americans: what should we advise patients about supplements?","volume":"65","author":"Blumberg","year":"2016","journal-title":"J Fam Pract"},{"key":"ref128","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.copbio.2012.08.005","article-title":"Bacteria as vitamin suppliers to their host: a gut microbiota perspective","volume":"24","author":"LeBlanc","year":"2013","journal-title":"Curr Opin Biotechnol"},{"key":"ref129","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1503\/cmaj.050342","article-title":"Malnutrition and health in developing countries","volume":"173","author":"M\u00fcller","year":"2005","journal-title":"CMAJ"},{"key":"ref130","doi-asserted-by":"publisher","first-page":"e02481","DOI":"10.1128\/mBio.02481-14","article-title":"Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide","volume":"6","author":"Romano","year":"2015","journal-title":"MBio"},{"key":"ref131","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.chom.2017.07.021","article-title":"Metabolic, epigenetic, and transgenerational effects of gut bacterial choline consumption","volume":"22","author":"Romano","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref132","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1126\/science.1229000","article-title":"Gut microbiomes of Malawian twin pairs discordant for kwashiorkor","volume":"339","author":"Smith","year":"2013","journal-title":"Science"},{"key":"ref133","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1194\/jlr.R036012","article-title":"The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism","volume":"54","author":"Den Besten","year":"2013","journal-title":"J Lipid Res"},{"key":"ref134","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/nyas.13145","article-title":"Nutrition meets the microbiome: micronutrients and the microbiota","volume":"1372","author":"Biesalski","year":"2016","journal-title":"Ann N Y Acad Sci"},{"key":"ref135","doi-asserted-by":"publisher","first-page":"e103318","DOI":"10.1371\/journal.pone.0103318","article-title":"Metagenomic identification of a novel salt tolerance gene from the human gut microbiome which encodes a membrane protein with homology to a brp\/blh-family \u03b2-carotene 15, 15\u2032-monooxygenase","volume":"9","author":"Culligan","year":"2014","journal-title":"PLoS One"},{"key":"ref136","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.cmet.2014.10.002","article-title":"Vitamin B12 as a modulator of gut microbial ecology","volume":"20","author":"Degnan","year":"2014","journal-title":"Cell Metab"},{"key":"ref137","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1111\/j.1749-6632.1959.tb53101.x","article-title":"Vitamin K deficiency in germfree rats","volume":"78","author":"Gustafsson","year":"1959","journal-title":"Ann N Y Acad Sci"},{"key":"ref138","doi-asserted-by":"publisher","first-page":"84","DOI":"10.3945\/ajcn.115.109496","article-title":"Fecal menaquinone profiles of overweight adults are associated with gut microbiota composition during a gut microbiota\u2013targeted dietary intervention","volume":"102","author":"Karl","year":"2015","journal-title":"Am J Clin Nutr"},{"key":"ref139","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.3945\/ajcn.110.002188","article-title":"High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health","volume":"93","author":"Russell","year":"2011","journal-title":"Am J Clin Nutr"},{"key":"ref140","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.chom.2012.08.003","article-title":"Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish","volume":"12","author":"Semova","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref141","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1126\/science.1080029","article-title":"A genomic view of the human-Bacteroides thetaiotaomicron symbiosis","volume":"299","author":"Xu","year":"2003","journal-title":"Science"},{"key":"ref142","doi-asserted-by":"publisher","first-page":"e1001221","DOI":"10.1371\/journal.pbio.1001221","article-title":"Recognition and degradation of plant cell wall polysaccharides by two human gut symbionts","volume":"9","author":"Martens","year":"2011","journal-title":"PLoS Biol"},{"key":"ref143","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.cmet.2011.02.018","article-title":"The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon","volume":"13","author":"Donohoe","year":"2011","journal-title":"Cell Metab"},{"key":"ref144","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1073\/pnas.0605374104","article-title":"Mechanisms underlying the resistance to diet-induced obesity in germ-free mice","volume":"104","author":"B\u00e4ckhed","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref145","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1093\/jn\/137.9.2043","article-title":"Protocatechuic acid is the major human metabolite of cyanidin-glucosides3","volume":"137","author":"Vitaglione","year":"2007","journal-title":"J Nutr"},{"key":"ref146","doi-asserted-by":"publisher","first-page":"21307","DOI":"10.1073\/pnas.1215689109","article-title":"Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme","volume":"109","author":"Craciun","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref147","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/S0021-9258(18)60325-4","article-title":"The biosynthesis of trimethylamine-N-oxide","volume":"237","author":"Baker","year":"1962","journal-title":"J Biol Chem"},{"key":"ref148","doi-asserted-by":"publisher","first-page":"326","DOI":"10.3390\/toxins8110326","article-title":"Trimethylamine N-oxide: the good, the bad and the unknown","volume":"8","author":"Velasquez","year":"2016","journal-title":"Toxins"},{"key":"ref149","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.trsl.2016.07.007","article-title":"Microbiome, trimethylamine N-oxide, and cardiometabolic disease","volume":"179","author":"Tang","year":"2017","journal-title":"Transl Res"},{"key":"ref150","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1124\/dmd.116.070615","article-title":"Trimethylamine and trimethylamine N-oxide, a flavin-containing monooxygenase 3 (FMO3)-mediated host-microbiome metabolic axis implicated in health and disease","volume":"44","author":"Fennema","year":"2016","journal-title":"Drug Metab Dispos"},{"key":"ref151","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.jnutbio.2017.08.004","article-title":"Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity","volume":"49","author":"Nam","year":"2017","journal-title":"J Nutr Biochem"},{"key":"ref152","doi-asserted-by":"publisher","first-page":"765","DOI":"10.3390\/nu9070765","article-title":"Maternal choline supplementation alters fetal growth patterns in a mouse model of placental insufficiency","volume":"9","author":"King","year":"2017","journal-title":"Nutrients"},{"key":"ref153","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1093\/ajcn\/80.3.539","article-title":"Betaine in human nutrition","volume":"80","author":"Craig","year":"2004","journal-title":"Am J Clin Nutr"},{"key":"ref154","doi-asserted-by":"publisher","first-page":"899","DOI":"10.3390\/nu9080899","article-title":"Choline supplementation normalizes fetal adiposity and reduces lipogenic gene expression in a mouse model of maternal obesity","volume":"9","author":"Jack-Roberts","year":"2017","journal-title":"Nutrients"},{"key":"ref155","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/S0021-9258(19)50785-2","article-title":"The function of cytidine coenzymes in the biosynthesis of phospholipides","volume":"222","author":"Kennedy","year":"1956","journal-title":"J Biol Chem"},{"key":"ref156","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S0022-2275(20)41538-X","article-title":"Regulation of hepatic secretion of very low density lipoprotein by dietary cholesterol","volume":"33","author":"Fungwe","year":"1992","journal-title":"J Lipid Res"},{"key":"ref157","doi-asserted-by":"publisher","first-page":"26745","DOI":"10.1038\/srep26745","article-title":"Relationship of serum trimethylamine N-oxide (TMAO) levels with early atherosclerosis in humans","volume":"6","author":"Randrianarisoa","year":"2016","journal-title":"Sci Rep"},{"key":"ref158","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1076\/apab.110.5.393.11832","article-title":"Free and phospholipid-bound choline concentrations in serum during pregnancy, after delivery and in newborns","volume":"110","author":"Ilcol","year":"2002","journal-title":"Arch Physiol Biochem"},{"key":"ref159","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0009-8981(85)90267-0","article-title":"Measurement of free choline concentrations in maternal and neonatal blood by micropyrolysis gas chromatography","volume":"149","author":"McMahon","year":"1985","journal-title":"Clin Chim Acta"},{"key":"ref160","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1017\/S1368980013003224","article-title":"Racial\/ethnic and sociodemographic factors associated with micronutrient intakes and inadequacies among pregnant women in an urban US population","volume":"17","author":"Brunst","year":"2014","journal-title":"Public Health Nutr"},{"key":"ref161","doi-asserted-by":"publisher","first-page":"2622","DOI":"10.1096\/fj.07-8227com","article-title":"Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes","volume":"21","author":"Resseguie","year":"2007","journal-title":"FASEB J"},{"key":"ref162","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.bbi.2023.10.031","article-title":"Priming of microglia with dysfunctional gut microbiota impairs hippocampal neurogenesis and fosters stress vulnerability of mice","volume":"115","author":"He","year":"2024","journal-title":"Brain Behav Immun"},{"key":"ref163","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.it.2022.10.009","article-title":"Prenatal inflammation shapes microglial immune response into adulthood","volume":"43","author":"Traetta","year":"2022","journal-title":"Trends Immunol"},{"key":"ref164","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.medmic.2025.100141","article-title":"Microbiota during pregnancy, childbirth, and postpartum, and its relationship with health and disease states","volume":"25","author":"Ibarra","year":"2025","journal-title":"Med. Microecol."},{"key":"ref165","doi-asserted-by":"publisher","first-page":"932309","DOI":"10.3389\/fcimb.2022.932309","article-title":"Gut microbiota: linking nutrition and perinatal depression","volume":"12","author":"Song","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"ref166","doi-asserted-by":"publisher","first-page":"3003","DOI":"10.1038\/s41467-024-47273-w","article-title":"Immunoregulatory role of the gut microbiota in inflammatory depression","volume":"15","author":"Liu","year":"2024","journal-title":"Nat Commun"},{"key":"ref167","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.bbi.2024.04.002","article-title":"Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model","volume":"119","author":"Xu","year":"2024","journal-title":"Brain Behav Immun"},{"key":"ref168","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nrn.2016.70","article-title":"Epigenetic mechanisms in neurogenesis","volume":"17","author":"Yao","year":"2016","journal-title":"Nat Rev Neurosci"},{"key":"ref169","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/bs.ampbs.2023.12.001","article-title":"Microbial metabolites as modulators of host physiology","volume":"84","author":"Joyce","year":"2024","journal-title":"Adv Microb Physiol"},{"key":"ref170","doi-asserted-by":"publisher","first-page":"105082","DOI":"10.1016\/j.phrs.2020.105082","article-title":"Butyrate, but not propionate, reverses maternal diet-induced neurocognitive deficits in offspring","volume":"160","author":"Yu","year":"2020","journal-title":"Pharmacol Res"},{"key":"ref171","doi-asserted-by":"publisher","first-page":"101982","DOI":"10.1016\/j.xcrm.2025.101982","article-title":"The gut microbiota-immune-brain axis: therapeutic implications","volume":"6","author":"O\u2019Riordan","year":"2025","journal-title":"Cell Rep Med"},{"key":"ref172","doi-asserted-by":"publisher","first-page":"31777","DOI":"10.1074\/jbc.M705539200","article-title":"Gestational choline deficiency causes global and Igf2 gene DNA hypermethylation by up-regulation of Dnmt1 expression","volume":"282","author":"Kovacheva","year":"2007","journal-title":"J Biol Chem"},{"key":"ref173","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.bbrc.2016.11.017","article-title":"Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome","volume":"481","author":"Sun","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"key":"ref174","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1093\/nutrit\/nuu001","article-title":"Impact of oxidative stress during pregnancy on fetal epigenetic patterns and early origin of vascular diseases","volume":"73","author":"Ortega \u00c1vila","year":"2015","journal-title":"Nutr Rev"},{"key":"ref175","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1096\/fj.15-282426","article-title":"Maternal dietary intake of choline in mice regulates development of the cerebral cortex in the offspring","volume":"30","author":"Wang","year":"2015","journal-title":"FASEB J"},{"key":"ref176","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1096\/fj.05-4707com","article-title":"Dietary choline deficiency alters global and gene-specific DNA methylation in the developing hippocampus of mouse fetal brains","volume":"20","author":"Niculescu","year":"2006","journal-title":"FASEB J"},{"key":"ref177","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1096\/fj.06-5734com","article-title":"Common genetic polymorphisms affect the human requirement for the nutrient choline","volume":"20","author":"Da Costa","year":"2006","journal-title":"FASEB J"},{"key":"ref178","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1074\/jbc.M110.106922","article-title":"Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction","volume":"286","author":"Resseguie","year":"2011","journal-title":"J Biol Chem"},{"key":"ref179","doi-asserted-by":"publisher","first-page":"e02113","DOI":"10.1128\/mBio.02113-14","article-title":"Gut microbiota as an epigenetic regulator: pilot study based on whole-genome methylation analysis","volume":"5","author":"Kumar","year":"2014","journal-title":"MBio"},{"key":"ref180","doi-asserted-by":"publisher","first-page":"107686","DOI":"10.1016\/j.psyneuen.2025.107686","article-title":"Gut feelings: dysbiosis of gut microbiota and short-chain fatty acids associated with prenatal depression, pregnancy-related anxiety, and prenatal combined depression and anxiety","author":"Fan","year":"2025","journal-title":"Psychoneuroendocrinology"},{"key":"ref181","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1007\/s11011-017-0178-y","article-title":"The role of tryptophan metabolism in postpartum depression","volume":"33","author":"Duan","year":"2018","journal-title":"Metab Brain Dis"},{"key":"ref182","doi-asserted-by":"publisher","first-page":"2000734","DOI":"10.1002\/mnfr.202000734","article-title":"One carbon metabolism and mammalian pregnancy outcomes","volume":"65","author":"Cai","year":"2021","journal-title":"Mol Nutr Food Res"},{"key":"ref183","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1523\/JNEUROSCI.1604-18.2018","article-title":"Enhancement of BDNF expression and memory by HDAC inhibition requires BET bromodomain reader proteins","volume":"39","author":"Sartor","year":"2019","journal-title":"J Neurosci"},{"key":"ref184","doi-asserted-by":"publisher","first-page":"1134080","DOI":"10.3389\/fnins.2023.1134080","article-title":"Serum short chain fatty acids mediate hippocampal BDNF and correlate with decreasing neuroinflammation following high pectin fiber diet in mice","volume":"17","author":"Church","year":"2023","journal-title":"Front Neurosci"},{"key":"ref185","doi-asserted-by":"publisher","first-page":"107838","DOI":"10.1016\/j.fbio.2025.107838","article-title":"Remember the gut: the emerging role of microbial SCFAs in cognitive health","author":"de Paiva","year":"2025","journal-title":"Food Biosci"},{"key":"ref186","doi-asserted-by":"publisher","first-page":"4504","DOI":"10.7150\/ijbs.112869","article-title":"New insights into coordinated regulation of AHR promoter transcription; molecular mechanisms and therapeutic targets","volume":"21","author":"Wuputra","year":"2025","journal-title":"Int J Biol Sci"},{"key":"ref187","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.bbi.2019.10.017","article-title":"Inflammation and kynurenine pathway dysregulation in post-partum women with severe and suicidal depression","volume":"83","author":"Achtyes","year":"2020","journal-title":"Brain Behav Immun"},{"key":"ref188","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/B978-0-12-817935-2.00046-5","volume-title":"The Neuroscience of Depression","author":"Sanblas","year":"2021"},{"key":"ref189","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/s41398-024-03148-8","article-title":"Association between maternal perinatal stress and depression and infant DNA methylation in the first year of life","volume":"14","author":"Abrishamcar","year":"2024","journal-title":"Transl Psychiatry"},{"key":"ref190","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41564-017-0075-5","article-title":"Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice","volume":"3","author":"Schulfer","year":"2018","journal-title":"Nat Microbiol"},{"key":"ref191","doi-asserted-by":"publisher","first-page":"15062","DOI":"10.1038\/ncomms15062","article-title":"Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior","volume":"8","author":"Leclercq","year":"2017","journal-title":"Nat Commun"},{"key":"ref192","doi-asserted-by":"publisher","first-page":"7611","DOI":"10.1073\/pnas.1620661114","article-title":"Social and physical environments early in development predict DNA methylation of inflammatory genes in young adulthood","volume":"114","author":"McDade","year":"2017","journal-title":"Proc Natl Acad Sci"},{"key":"ref193","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.3945\/ajcn.115.126375","article-title":"Alterations in human milk leptin and insulin are associated with early changes in the infant intestinal microbiome","volume":"103","author":"Lemas","year":"2016","journal-title":"Am J Clin Nutr"},{"key":"ref194","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nrendo.2015.128","article-title":"Short-chain fatty acids in control of body weight and insulin sensitivity","volume":"11","author":"Canfora","year":"2015","journal-title":"Nat Rev Endocrinol"},{"key":"ref195","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"ref196","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nature18309","article-title":"Acetate mediates a microbiome\u2013brain\u2013\u03b2-cell axis to promote metabolic syndrome","volume":"534","author":"Perry","year":"2016","journal-title":"Nature"},{"key":"ref197","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.molcel.2016.10.025","article-title":"Diet-microbiota interactions mediate global epigenetic programming in multiple host tissues","volume":"64","author":"Krautkramer","year":"2016","journal-title":"Mol Cell"},{"key":"ref198","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1080\/1028415X.2022.2110664","article-title":"Probiotics supplementation and brain-derived neurotrophic factor (BDNF): a systematic review and meta-analysis of randomized controlled trials","volume":"26","author":"Dehghani","year":"2023","journal-title":"Nutr Neurosci"},{"key":"ref199","doi-asserted-by":"publisher","first-page":"e70205","DOI":"10.1002\/fft2.70205","article-title":"Postbiotics in functional foods: microbial derivatives shaping health, immunity and next-generation nutrition","volume":"7","author":"Mafe","year":"2026","journal-title":"Food Front"},{"key":"ref200","doi-asserted-by":"publisher","first-page":"e37114","DOI":"10.1097\/MD.0000000000037114","article-title":"The correlation between gut microbiota and both neurotransmitters and mental disorders: a narrative review","volume":"103","author":"Mhanna","year":"2024","journal-title":"Medicine"},{"key":"ref201","doi-asserted-by":"publisher","first-page":"1644160","DOI":"10.3389\/fimmu.2025.1644160","article-title":"The microbiota-gut-brain axis in depression: unraveling the relationships and therapeutic opportunities","volume":"16","author":"Zhu","year":"2025","journal-title":"Front Immunol"},{"key":"ref202","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1089\/biores.2012.0223","article-title":"Butyrate histone deacetylase inhibitors","volume":"1","author":"Steliou","year":"2012","journal-title":"Biores Open Access"},{"key":"ref203","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.pnpbp.2015.03.010","article-title":"The potential use of histone deacetylase inhibitors in the treatment of depression","volume":"64","author":"Fuchikami","year":"2016","journal-title":"Prog Neuro-Psychopharmacol Biol Psychiatry"},{"key":"ref204","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.3390\/ijms24032346","article-title":"Methyl donors, epigenetic alterations, and brain health: understanding the connection","volume":"24","author":"Bekdash","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref205","doi-asserted-by":"publisher","first-page":"104611","DOI":"10.1016\/j.psyneuen.2020.104611","article-title":"The role of glucocorticoid and mineralocorticoid receptor DNA methylation in antenatal depression and infant stress regulation","volume":"115","author":"Galbally","year":"2020","journal-title":"Psychoneuroendocrinology"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1778348\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T06:38:23Z","timestamp":1773988703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1778348\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":205,"alternative-id":["10.3389\/fmed.2026.1778348"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1778348","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,20]]},"article-number":"1778348"}}