Psychiatric and mood disorders may play an important role in the development and persistence of irritable bowel syndrome (IBS). Previously, we hypothesized that stress-induced implicit memories may persist throughout life via epigenetic processes in the enteric nervous system (ENS), independent of the central nervous system (CNS). These epigenetic memories in the ENS may contribute to developing and perpetuating IBS. Here, we further elaborate on our earlier hypothesis. That is, during pregnancy, maternal prenatal stresses perturb the HPA axis and increase circulating cortisol levels, which can affect the maternal gut microbiota. Maternal cortisol can cross the placental barrier and increase cortisol-circulating levels in the fetus. This leads to dysregulation of the HPA axis, affecting the gut microbiota, microbial metabolites, and intestinal permeability in the fetus. Microbial metabolites, such as short-chain fatty acids (which also regulate the development of fetal ENS), can modulate a range of diseases by inducing epigenetic changes. These mentioned processes suggest that stress-related, implicit, long-term epigenetic memories may be programmed into the fetal ENS during pregnancy. Subsequently, this implicit epigenetic stress information from the fetal ENS could be conveyed to the CNS through the bidirectional microbiota-gut-brain axis (MGBA), leading to perturbed functional connectivity among various brain networks and the dysregulation of affective and pain processes.

Center for Neuropsychiatric Research of Traumatic Stress Department of Psychiatry and UHSL 1st Faculty of Medicine and Department of Psychiatry Faculty of Medicine Pilsen Charles University CZ 12108 Prague Czechia

National University of Public Services H 1083 Budapest Hungary

Neuroscience and Consciousness Research Department Vision Research Institute Lowell MA 01854 USA

Psychosomatic Outpatient Clinics H 1037 Budapest Hungary

See more in PubMed

Chen J., Barandouzi Z.A., Lee J., Xu W., Feng B., Starkweather A., Cong X. Psychosocial and sensory factors contribute to self-reported pain and quality of life in young adults with irritable bowel syndrome. Pain Manag. Nurs. 2022;23(5):646–654. doi: 10.1016/j.pmn.2021.12.004. PubMed DOI PMC

Tripathi R., Mehrotra S. Irritable bowel syndrome and its psychological management. Ind. Psychiatry J. 2015;24(1):91–93. doi: 10.4103/0972-6748.160947. PubMed DOI PMC

van Tilburg M.A.L., Palsson O.S., Whitehead W.E. Which psychological factors exacerbate irritable bowel syndrome? Development of a comprehensive model. J. Psychosom. Res. 2013;74(6):486–492. doi: 10.1016/j.jpsychores.2013.03.004. PubMed DOI PMC

Sharkey K.A., Mawe G.M. The enteric nervous system. Physiol. Rev. 2023;103(2):1487–1564. doi: 10.1152/physrev.00018.2022. PubMed DOI PMC

Furness J.B. Comparative and evolutionary aspects of the digestive system and its enteric nervous system control. Adv. Exp. Med. Biol. 2022;1383:165–177. doi: 10.1007/978-3-031-05843-1_16. PubMed DOI

Green S.A., Uy B.R., Bronner M.E. Ancient evolutionary origin of vertebrate enteric neurons from trunk-derived neural crest. Nature. 2017;544(7648):88–91. doi: 10.1038/nature21679. PubMed DOI PMC

Furness J.B., Stebbing M.J. The first brain: Species comparisons and evolutionary implications for the enteric and central nervous systems. Neurogastroenterol. Motil. 2018;30(2):e13234. doi: 10.1111/nmo.13234. PubMed DOI

Császár-Nagy N., Bókkon I. Hypnotherapy and IBS: Implicit, long-term stress memory in the ENS? Heliyon. 2023;9(1):e12751. doi: 10.1016/j.heliyon.2022.e12751. PubMed DOI PMC

Mao C.P., Chen F.R., Huo J.H., Zhang L., Zhang G.R., Zhang B., Zhou X.Q. Altered resting‐state functional connectivity and effective connectivity of the habenula in irritable bowel syndrome: A cross‐sectional and machine learning study. Hum. Brain Mapp. 2020;41(13):3655–3666. doi: 10.1002/hbm.25038. PubMed DOI PMC

Weng Y., Qi R., Liu C., Ke J., Xu Q., Wang F., Zhang L.J., Lu G.M. Disrupted functional connectivity density in irritable bowel syndrome patients. Brain Imaging Behav. 2017;11(6):1812–1822. doi: 10.1007/s11682-016-9653-z. PubMed DOI

Bhatt R.R., Gupta A., Labus J.S., Zeltzer L.K., Tsao J.C., Shulman R.J., Tillisch K. Altered brain structure and functional connectivity and its relation to pain perception in girls with irritable bowel syndrome. Psychosom. Med. 2019;81(2):146–154. doi: 10.1097/PSY.0000000000000655. PubMed DOI PMC

Nisticò V., Rossi R.E., D’Arrigo A.M., Priori A., Gambini O., Demartini B. Functional neuroimaging in irritable bowel syndrome: A systematic review highlights common brain alterations with functional movement disorders. J. Neurogastroenterol. Motil. 2022;28(2):185–203. doi: 10.5056/jnm21079. PubMed DOI PMC

Qi R., Liu C., Weng Y., Xu Q., Chen L., Wang F., Zhang L.J., Lu G.M. Disturbed interhemispheric functional connectivity rather than structural connectivity in irritable bowel syndrome. Front. Mol. Neurosci. 2016;9:141. doi: 10.3389/fnmol.2016.00141. PubMed DOI PMC

Li J., He P., Lu X., Guo Y., Liu M., Li G., Ding J. A resting-state functional magnetic resonance imaging study of whole-brain functional connectivity of voxel levels in patients with irritable bowel syndrome with depressive symptoms. J. Neurogastroenterol. Motil. 2021;27(2):248–256. doi: 10.5056/jnm20209. PubMed DOI PMC

Martinou E., Stefanova I., Iosif E., Angelidi A.M. Neurohormonal changes in the gut-brain axis and underlying neuroendocrine mechanisms following bariatric surgery. Int. J. Mol. Sci. 2022;23(6):3339. doi: 10.3390/ijms23063339. PubMed DOI PMC

Carabotti M., Scirocco A., Maselli M.A., Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. 2015;28(2):203–209. PubMed PMC

Muhammad F., Fan B., Wang R., Ren J., Jia S., Wang L., Chen Z., Liu X.A. The molecular gut-brain axis in early brain development. Int. J. Mol. Sci. 2022;23(23):15389. doi: 10.3390/ijms232315389. PubMed DOI PMC

Sarubbo F., Cavallucci V., Pani G. The influence of gut microbiota on neurogenesis: Evidence and hopes. Cells. 2022;11(3):382. doi: 10.3390/cells11030382. PubMed DOI PMC

Song J.G., Yu M.S., Lee B., Lee J., Hwang S.H., Na D., Kim H.W. Analysis methods for the gut microbiome in neuropsychiatric and neurodegenerative disorders. Comput. Struct. Biotechnol. J. 2022;20:1097–1110. doi: 10.1016/j.csbj.2022.02.024. PubMed DOI PMC

Wachsmuth H.R., Weninger S.N., Duca F.A. Role of the gut–brain axis in energy and glucose metabolism. Exp. Mol. Med. 2022;54(4):377–392. doi: 10.1038/s12276-021-00677-w. PubMed DOI PMC

Chakrabarti A., Geurts L., Hoyles L., Iozzo P., Kraneveld A.D., La Fata G., Miani M., Patterson E., Pot B., Shortt C., Vauzour D. The microbiota-gut-brain axis: Pathways to better brain health. Perspectives on what we know, what we need to investigate and how to put knowledge into practice. Cell. Mol. Life Sci. 2022;79(2):80. doi: 10.1007/s00018-021-04060-w. PubMed DOI PMC

Rutsch A., Kantsjö J.B., Ronchi F. The gut-brain axis: How microbiota and host inflammasome influence brain physiology and pathology. Front. Immunol. 2020;11:604179. doi: 10.3389/fimmu.2020.604179. PubMed DOI PMC

Karl J.P., Hatch A.M., Arcidiacono S.M., Pearce S.C., Feliciano P.I.G., Doherty L.A., Soares J.W. Effects of psychological, environmental and physical stressors on the gut microbiota. Front. Microbiol. 2018;9:2013. doi: 10.3389/fmicb.2018.02013. PubMed DOI PMC

Gebrayel P., Nicco C., Al Khodor S., Bilinski J., Caselli E., Comelli E.M., Egert M., Giaroni C., Karpinski T.M., Loniewski I., Mulak A., Reygner J., Samczuk P., Serino M., Sikora M., Terranegra A., Ufnal M., Villeger R., Pichon C., Konturek P., Edeas M. Microbiota medicine: Towards clinical revolution. J. Transl. Med. 2022;20(1):111. doi: 10.1186/s12967-022-03296-9. PubMed DOI PMC

Afzaal M., Saeed F., Shah Y.A., Hussain M., Rabail R., Socol C.T., Hassoun A., Pateiro M., Lorenzo J.M., Rusu A.V., Aadil R.M. Human gut microbiota in health and disease: Unveiling the relationship. Front. Microbiol. 2022;13:999001. doi: 10.3389/fmicb.2022.999001. PubMed DOI PMC

Chidambaram S.B., Essa M.M., Rathipriya A.G., Bishir M., Ray B., Mahalakshmi A.M., Tousif A.H., Sakharkar M.K., Kashyap R.S., Friedland R.P., Monaghan T.M. Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle. Pharmacol. Ther. 2022;231:107988. doi: 10.1016/j.pharmthera.2021.107988. PubMed DOI

Carding S., Verbeke K., Vipond D.T., Corfe B.M., Owen L.J. Dysbiosis of the gut microbiota in disease. Microb. Ecol. Health Dis. 2015;26:26191. PubMed PMC

Scriven M., Dinan T., Cryan J., Wall M. Neuropsychiatric disorders: Influence of gut microbe to brain signalling. Diseases. 2018;6(3):78. doi: 10.3390/diseases6030078. PubMed DOI PMC

Sandhu K.V., Sherwin E., Schellekens H., Stanton C., Dinan T.G., Cryan J.F. Feeding the microbiota-gut-brain axis: Diet, microbiome, and neuropsychiatry. Transl. Res. 2017;179:223–244. doi: 10.1016/j.trsl.2016.10.002. PubMed DOI

Socała K., Doboszewska U., Szopa A., Serefko A., Włodarczyk M., Zielińska A., Poleszak E., Fichna J., Wlaź P. The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders. Pharmacol. Res. 2021;172:105840. doi: 10.1016/j.phrs.2021.105840. PubMed DOI

Zang Y., Lai X., Li C., Ding D., Wang Y., Zhu Y. The role of gut microbiota in various neurological and psychiatric disorders-an evidence mapping based on quantified evidence. Mediators Inflamm. 2023;2023:1–16. doi: 10.1155/2023/5127157. PubMed DOI PMC

Suganya K., Koo B.S. Gut-brain axis: Role of gut microbiota on neurological disorders and how probiotics/prebiotics beneficially modulate microbial and immune pathways to improve brain functions. Int. J. Mol. Sci. 2020;21(20):7551. doi: 10.3390/ijms21207551. PubMed DOI PMC

Abo-Shaban T., Sharna S.S., Hosie S., Lee C.Y.Q., Balasuriya G.K., McKeown S.J., Franks A.E., Yardin H.E.L. Issues for patchy tissues: Defining roles for gut-associated lymphoid tissue in neurodevelopment and disease. J. Neural Transm. 2023;130(3):269–280. doi: 10.1007/s00702-022-02561-x. PubMed DOI PMC

Agustí A., Pardo G.M.P., Almela L.I., Campillo I., Maes M., Pérez R.M., Sanz Y. Interplay between the gut-brain axis, obesity and cognitive function. Front. Neurosci. 2018;12:155. doi: 10.3389/fnins.2018.00155. PubMed DOI PMC

Rudzki L., Maes M. The microbiota-gut-immune-glia (MGIG) axis in major depression. Mol. Neurobiol. 2020;57(10):4269–4295. doi: 10.1007/s12035-020-01961-y. PubMed DOI

Clapp M., Aurora N., Herrera L., Bhatia M., Wilen E., Wakefield S. Gut microbiota’s effect on mental health: The gut-brain axis. Clin. Pract. 2017;7(4):987. doi: 10.4081/cp.2017.987. PubMed DOI PMC

Berk M., Williams L.J., Jacka F.N., O’Neil A., Pasco J.A., Moylan S., Allen N.B., Stuart A.L., Hayley A.C., Byrne M.L., Maes M. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013;11(1):200. doi: 10.1186/1741-7015-11-200. PubMed DOI PMC

Maes M., Vasupanrajit A., Jirakran K., Klomkliew P., Chanchaem P., Tunvirachaisakul C., Plaimas K., Suratanee A., Payungporn S. Adverse childhood experiences and reoccurrence of illness impact the gut microbiome, which affects suicidal behaviours and the phenome of major depression: Towards enterotypic phenotypes. Acta Neuropsychiatr. 2023;35(6):328–345. doi: 10.1017/neu.2023.21. PubMed DOI

Maes M., Yirmyia R., Noraberg J., Brene S., Hibbeln J., Perini G., Kubera M., Bob P., Lerer B., Maj M. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab. Brain Dis. 2009;24(1):27–53. doi: 10.1007/s11011-008-9118-1. PubMed DOI

Rudzki L., Maes M. From “Leaky Gut” to impaired glia-neuron communication in depression. Adv. Exp. Med. Biol. 2021;1305:129–155. doi: 10.1007/978-981-33-6044-0_9. PubMed DOI

Martínez R.S., Real S.L., García G.A.P., Cruz T.E., Jonapa C.L.A., Amedei A., García A.M.M. Neuroinflammation, microbiota-gut-brain axis, and depression: The vicious circle. J. Integr. Neurosci. 2023;22(3):65. doi: 10.31083/j.jin2203065. PubMed DOI

Qin H.Y., Cheng C.W., Tang X.D., Bian Z.X. Impact of psychological stress on irritable bowel syndrome. World J. Gastroenterol. 2014;20(39):14126–14131. doi: 10.3748/wjg.v20.i39.14126. PubMed DOI PMC

Belei O., Basaca D.G., Olariu L., Pantea M., Bozgan D., Nanu A., Sîrbu I., Mărginean O., Enătescu I. The interaction between stress and inflammatory bowel disease in pediatric and adult patients. J. Clin. Med. 2024;13(5):1361. doi: 10.3390/jcm13051361. PubMed DOI PMC

Howland R.H. Vagus nerve stimulation. Curr. Behav. Neurosci. Rep. 2014;1(2):64–73. doi: 10.1007/s40473-014-0010-5. PubMed DOI PMC

Berthoud H.R., Neuhuber W.L. Functional and chemical anatomy of the afferent vagal system. Auton. Neurosci. 2000;85(1-3):1–17. doi: 10.1016/S1566-0702(00)00215-0. PubMed DOI

Forsythe P., Bienenstock J., Kunze W.A. Vagal pathways for microbiome-brain-gut axis communication. Adv. Exp. Med. Biol. 2014;817:115–133. doi: 10.1007/978-1-4939-0897-4_5. PubMed DOI

Latorre R., Sternini C., Giorgio D.R., Meerveld G.V.B. Enteroendocrine cells: A review of their role in brain–gut communication. Neurogastroenterol. Motil. 2016;28(5):620–630. doi: 10.1111/nmo.12754. PubMed DOI PMC

Kanai T., Teratani T. Role of the vagus nerve in the gut-brain axis: Development and maintenance of gut regulatory T cells via the liver-brain-gut vago-vagal reflex. Brain Nerve. 2022;74(8):971–977. PubMed

Han Y., Wang B., Gao H., He C., Hua R., Liang C., Zhang S., Wang Y., Xin S., Xu J. Vagus nerve and underlying impact on the gut microbiota-brain axis in behavior and neurodegenerative diseases. J. Inflamm. Res. 2022;15:6213–6230. doi: 10.2147/JIR.S384949. PubMed DOI PMC

Chang L., Wei Y., Hashimoto K. Brain–gut–microbiota axis in depression: A historical overview and future directions. Brain Res. Bull. 2022;182:44–56. doi: 10.1016/j.brainresbull.2022.02.004. PubMed DOI

Garg K., Mohajeri M.H. Potential effects of the most prescribed drugs on the microbiota-gut-brain-axis: A review. Brain Res. Bull. 2024;207:110883. doi: 10.1016/j.brainresbull.2024.110883. PubMed DOI

Vich Vila A., Collij V., Sanna S., Sinha T., Imhann F., Bourgonje A.R., Mujagic Z., Jonkers D.M.A.E., Masclee A.A.M., Fu J., Kurilshikov A., Wijmenga C., Zhernakova A., Weersma R.K. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat. Commun. 2020;11(1):362. doi: 10.1038/s41467-019-14177-z. PubMed DOI PMC

Karakan T., Ozkul C., Akkol K.E., Bilici S., Sánchez S.E., Capasso R. Gut-brain-microbiota axis: Antibiotics and functional gastrointestinal disorders. Nutrients. 2021;13(2):389. doi: 10.3390/nu13020389. PubMed DOI PMC

Maier L., Pruteanu M., Kuhn M., Zeller G., Telzerow A., Anderson E.E., Brochado A.R., Fernandez K.C., Dose H., Mori H., Patil K.R., Bork P., Typas A. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555(7698):623–628. doi: 10.1038/nature25979. PubMed DOI PMC

Essmat N., Karádi D.Á., Zádor F., Király K., Fürst S., Khrasani A.M. Insights into the current and possible future use of opioid antagonists in relation to opioid-induced constipation and dysbiosis. Molecules. 2023;28(23):7766. doi: 10.3390/molecules28237766. PubMed DOI PMC

Bernabè G., Shalata M.E.M., Zatta V., Bellato M., Porzionato A., Castagliuolo I., Brun P. Antibiotic treatment induces long-lasting effects on gut microbiota and the enteric nervous system in mice. Antibiotics. 2023;12(6):1000. doi: 10.3390/antibiotics12061000. PubMed DOI PMC

Caparrós-Martín J.A., Lareu R.R., Ramsay J.P., Peplies J., Reen F.J., Headlam H.A., Ward N.C., Croft K.D., Newsholme P., Hughes J.D., O’Gara F. Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism. Microbiome. 2017;5(1):95. doi: 10.1186/s40168-017-0312-4. PubMed DOI PMC

Doestzada M., Vila A.V., Zhernakova A., Koonen D.P.Y., Weersma R.K., Touw D.J., Kuipers F., Wijmenga C., Fu J. Pharmacomicrobiomics: A novel route towards personalized medicine? Protein Cell. 2018;9(5):432–445. doi: 10.1007/s13238-018-0547-2. PubMed DOI PMC

Crişan I.M., Dumitraşcu D.L. Irritable bowel syndrome: Peripheral mechanisms and therapeutic implications. Clujul Med. 2014;87(2):73–79. PubMed PMC

Saha L. Irritable bowel syndrome: Pathogenesis, diagnosis, treatment, and evidence-based medicine. World J. Gastroenterol. 2014;20(22):6759–6773. doi: 10.3748/wjg.v20.i22.6759. PubMed DOI PMC

Weaver K.R., Melkus G.D.E., Henderson W.A. Irritable bowel syndrome. Am. J. Nurs. 2017;117(6):48–55. doi: 10.1097/01.NAJ.0000520253.57459.01. PubMed DOI PMC

Lee Y.J., Park K.S. Irritable bowel syndrome: Emerging paradigm in pathophysiology. World J. Gastroenterol. 2014;20(10):2456–2469. doi: 10.3748/wjg.v20.i10.2456. PubMed DOI PMC

Chong P.P., Chin V.K., Looi C.Y., Wong W.F., Madhavan P., Yong V.C. The microbiome and irritable bowel syndrome - A review on the pathophysiology, current research and future therapy. Front. Microbiol. 2019;10:1136. doi: 10.3389/fmicb.2019.01136. PubMed DOI PMC

Oka P., Parr H., Barberio B., Black C.J., Savarino E.V., Ford A.C. Global prevalence of irritable bowel syndrome according to Rome III or IV criteria: A systematic review and meta-analysis. Lancet Gastroenterol. Hepatol. 2020;5(10):908–917. doi: 10.1016/S2468-1253(20)30217-X. PubMed DOI

Camilleri M. Diagnosis and treatment of irritable bowel syndrome: A review. JAMA. 2021;325(9):865–877. doi: 10.1001/jama.2020.22532. PubMed DOI

Dinic R.B., Rajkovic T.S., Grgov S., Petrovic G., Zivkovic V. Irritable bowel syndrome - From etiopathogenesis to therapy. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 2018;162(1):1–9. doi: 10.5507/bp.2017.057. PubMed DOI

Rodiño-Janeiro B.K., Vicario M., Cotoner A.C., García P.R., Santos J. A review of microbiota and irritable bowel syndrome: Future in therapies. Adv. Ther. 2018;35(3):289–310. doi: 10.1007/s12325-018-0673-5. PubMed DOI PMC

Black C.J., Thakur E.R., Houghton L.A., Quigley E.M.M., Moayyedi P., Ford A.C. Efficacy of psychological therapies for irritable bowel syndrome: Systematic review and network meta-analysis. Gut. 2020;69(8):1441–1451. doi: 10.1136/gutjnl-2020-321191. PubMed DOI

Grundmann O., Yoon S.L. Irritable bowel syndrome: Epidemiology, diagnosis and treatment: An update for health‐care practitioners. J. Gastroenterol. Hepatol. 2010;25(4):691–699. doi: 10.1111/j.1440-1746.2009.06120.x. PubMed DOI

Staudacher H.M., Walus M.A., Ford A.C. Common mental disorders in irritable bowel syndrome: pathophysiology, management, and considerations for future randomised controlled trials. Lancet Gastroenterol. Hepatol. 2021;6(5):401–410. doi: 10.1016/S2468-1253(20)30363-0. PubMed DOI

Juruena M.F., Eror F., Cleare A.J., Young A.H. The role of early life stress in HPA axis and anxiety. Adv. Exp. Med. Biol. 2020;1191:141–153. doi: 10.1007/978-981-32-9705-0_9. PubMed DOI

Distrutti E., Monaldi L., Ricci P., Fiorucci S. Gut microbiota role in irritable bowel syndrome: New therapeutic strategies. World J. Gastroenterol. 2016;22(7):2219–2241. doi: 10.3748/wjg.v22.i7.2219. PubMed DOI PMC

Occhipinti K., Smith J. Irritable bowel syndrome: A review and update. Clin. Colon Rectal Surg. 2012;25(1):046–052. doi: 10.1055/s-0032-1301759. PubMed DOI PMC

Kano M., Muratsubaki T., Van Oudenhove L., Morishita J., Yoshizawa M., Kohno K., Yagihashi M., Tanaka Y., Mugikura S., Dupont P., Ly H.G., Takase K., Kanazawa M., Fukudo S. Altered brain and gut responses to corticotropin-releasing hormone (CRH) in patients with irritable bowel syndrome. Sci. Rep. 2017;7(1):12425. doi: 10.1038/s41598-017-09635-x. PubMed DOI PMC

Tarar Z.I., Farooq U., Zafar Y., Gandhi M., Raza S., Kamal F., Tarar M.F., Ghouri Y.A. Burden of anxiety and depression among hospitalized patients with irritable bowel syndrome: A nationwide analysis. Ir. J. Med. Sci. 2023;192(5):2159–2166. doi: 10.1007/s11845-022-03258-6. PubMed DOI

Eijsbouts C., Zheng T., Kennedy N.A., Bonfiglio F., Anderson C.A., Moutsianas L., Holliday J., Shi J., Shringarpure S., Agee M., Aslibekyan S., Auton A., Bell R.K., Bryc K., Clark S.K., Elson S.L., Brant K., Fontanillas P., Furlotte N.A., Gandhi P.M., Heilbron K., Hicks B., Hinds D.A., Huber K.E., Jewett E.M., Jiang Y., Kleinman A., Lin K-H., Litterman N.K., Luff M.K., McCreight J.C., McIntyre M.H., McManus K.F., Mountain J.L., Mozaffari S.V., Nandakumar P., Noblin E.S., Northover C.A.M., O’Connell J., Petrakovitz A.A., Pitts S.J., Poznik G.D., Sathirapongsasuti J.F., Shastri A.J., Shelton J.F., Tian C., Tung J.Y., Tunney R.J., Vacic V., Wang X., Zare A.S., Voda A-I., Kashyap P., Chang L., Mayer E., Heitkemper M., Sayuk G.S., Kulka R.T., Ringel Y., Chey W.D., Eswaran S., Merchant J.L., Shulman R.J., Bujanda L., Etxebarria G.K., Dlugosz A., Lindberg G., Schmidt P.T., Karling P., Ohlsson B., Walter S., Faresjö Å.O., Simren M., Halfvarson J., Portincasa P., Barbara G., Satta U.P., Neri M., Nardone G., Cuomo R., Galeazzi F., Bellini M., Latiano A., Houghton L., Jonkers D., Kurilshikov A., Weersma R.K., Netea M., Tesarz J., Gauss A., Stengel G.M., Andresen V., Frieling T., Pehl C., Schaefert R., Niesler B., Lieb W., Hanevik K., Langeland N., Wensaas K-A., Litleskare S., Gabrielsen M.E., Thomas L., Thijs V., Lemmens R., Van Oudenhove L., Wouters M., Farrugia G., Franke A., Hübenthal M., Abecasis G., Zawistowski M., Skogholt A.H., Jensen N.E., Hveem K., Esko T., Laving T.M., Zhernakova A., Camilleri M., Boeckxstaens G., Whorwell P.J., Spiller R., McVean G., D’Amato M., Jostins L., Parkes M. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nat. Genet. 2021;53(11):1543–1552. doi: 10.1038/s41588-021-00950-8. PubMed DOI PMC

Aziz M., Kumar J., Nawawi M.K., Ali R.R., Mokhtar N. Irritable bowel syndrome, depression, and neurodegeneration: A bidirectional communication from gut to brain. Nutrients. 2021;13(9):3061. doi: 10.3390/nu13093061. PubMed DOI PMC

Midenfjord I., Polster A., Sjövall H., Törnblom H., Simrén M. Anxiety and depression in irritable bowel syndrome: Exploring the interaction with other symptoms and pathophysiology using multivariate analyses. Neurogastroenterol. Motil. 2019;31(8):e13619. doi: 10.1111/nmo.13619. PubMed DOI

Ng Q.X., Soh A.Y.S., Loke W., Venkatanarayanan N., Lim D.Y., Yeo W.S. Systematic review with meta‐analysis: The association between post‐traumatic stress disorder and irritable bowel syndrome. J. Gastroenterol. Hepatol. 2019;34(1):68–73. doi: 10.1111/jgh.14446. PubMed DOI

Creed F. Risk factors for self-reported irritable bowel syndrome with prior psychiatric disorder: The lifelines cohort study. J. Neurogastroenterol. Motil. 2022;28(3):442–453. doi: 10.5056/jnm21041. PubMed DOI PMC

Fadgyas-Stanculete M., Buga A.M., Popa-Wagner A., Dumitrascu D.L. The relationship between irritable bowel syndrome and psychiatric disorders: From molecular changes to clinical manifestations. J. Mol. Psychiatry. 2014;2(1):4. doi: 10.1186/2049-9256-2-4. PubMed DOI PMC

Lydiard R.B., Falsetti S.A. Experience with anxiety and depression treatment studies: implications for designing irritable bowel syndrome clinical trials. Am. J. Med. 1999;107(5):65–73. doi: 10.1016/S0002-9343(99)00082-0. PubMed DOI

Tao E., Long G., Yang T., Chen B., Guo R., Ye D., Fang M., Jiang M. Maternal separation induced visceral hypersensitivity evaluated via novel and small size distention balloon in post-weaning mice. Front. Neurosci. 2022;15:803957. doi: 10.3389/fnins.2021.803957. PubMed DOI PMC

Ge L., Liu S., Li S., Yang J., Hu G., Xu C., Song W. Psychological stress in inflammatory bowel disease: Psychoneuroimmunological insights into bidirectional gut–brain communications. Front. Immunol. 2022;13:1016578. doi: 10.3389/fimmu.2022.1016578. PubMed DOI PMC

Sun Y., Xie R., Li L., Jin G., Zhou B., Huang H., Li M., Yang Y., Liu X., Cao X., Wang B., Liu W., Jiang K., Cao H. Prenatal maternal stress exacerbates experimental colitis of offspring in adulthood. Front. Immunol. 2021;12:700995. doi: 10.3389/fimmu.2021.700995. PubMed DOI PMC

Császár-Nagy N., Bókkon I. Mother-newborn separation at birth in hospitals: A possible risk for neurodevelopmental disorders? Neurosci. Biobehav. Rev. 2018;84:337–351. doi: 10.1016/j.neubiorev.2017.08.013. PubMed DOI

Bradford K., Shih W., Videlock E.J., Presson A.P., Naliboff B.D., Mayer E.A., Chang L. Association between early adverse life events and irritable bowel syndrome. Clin. Gastroenterol. Hepatol. 2012;10(4):385–390.e1. doi: 10.1016/j.cgh.2011.12.018. PubMed DOI PMC

Chitkara D.K., van Tilburg M.A.L., Martin B.N., Whitehead W.E. Early life risk factors that contribute to irritable bowel syndrome in adults: A systematic review. Am. J. Gastroenterol. 2008;103(3):765–774. doi: 10.1111/j.1572-0241.2007.01722.x. PubMed DOI PMC

Videlock E.J., Chang L. Latest insights on the pathogenesis of irritable bowel syndrome. Gastroenterol. Clin. North Am. 2021;50(3):505–522. doi: 10.1016/j.gtc.2021.04.002. PubMed DOI

Tang H.Y., Jiang A.J., Wang X.Y., Wang H., Guan Y.Y., Li F., Shen G.M. Uncovering the pathophysiology of irritable bowel syndrome by exploring the gut-brain axis: A narrative review. Ann. Transl. Med. 2021;9(14):1187. doi: 10.21037/atm-21-2779. PubMed DOI PMC

Salhy E.M. Irritable bowel syndrome: Diagnosis and pathogenesis. World J. Gastroenterol. 2012;18(37):5151–5163. doi: 10.3748/wjg.v18.i37.5151. PubMed DOI PMC

Gieryńska M., Szulc-Dąbrowska L., Struzik J., Mielcarska M.B., Zboroch G.K.P. Integrity of the intestinal barrier: the involvement of epithelial cells and microbiota-a mutual relationship. Animals. 2022;12(2):145. doi: 10.3390/ani12020145. PubMed DOI PMC

Gritz E.C., Bhandari V. The human neonatal gut microbiome: A brief review. Front Pediatr. 2015;3:17. PubMed PMC

Wu H.J., Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes. 2012;3(1):4–14. doi: 10.4161/gmic.19320. PubMed DOI PMC

Ng Q.X., Soh A.Y.S., Loke W., Lim D.Y., Yeo W.S. The role of inflammation in irritable bowel syndrome (IBS). J. Inflamm. Res. 2018;11:345–349. doi: 10.2147/JIR.S174982. PubMed DOI PMC

Shi N., Li N., Duan X., Niu H. Interaction between the gut microbiome and mucosal immune system. Mil. Med. Res. 2017;4(1):14. doi: 10.1186/s40779-017-0122-9. PubMed DOI PMC

Lazaridis N., Germanidis G. Current insights into the innate immune system dysfunction in irritable bowel syndrome. Ann. Gastroenterol. 2018;31(2):171–187. doi: 10.20524/aog.2018.0229. PubMed DOI PMC

Akiho H., Ihara E., Nakamura K. Low-grade inflammation plays a pivotal role in gastrointestinal dysfunction in irritable bowel syndrome. World J. Gastrointest. Pathophysiol. 2010;1(3):97–105. doi: 10.4291/wjgp.v1.i3.97. PubMed DOI PMC

El-Hakim Y., Bake S., Mani K.K., Sohrabji F. Impact of intestinal disorders on central and peripheral nervous system diseases. Neurobiol. Dis. 2022;165:105627. doi: 10.1016/j.nbd.2022.105627. PubMed DOI

Lu S., Jiang H., Shi Y. Association between irritable bowel syndrome and Parkinson’s disease: A systematic review and meta‐analysis. Acta Neurol. Scand. 2022;145(4):442–448. doi: 10.1111/ane.13570. PubMed DOI

Yoon S.Y., Shin J., Heo S.J., Chang J.S., Sunwoo M.K., Kim Y.W. Irritable bowel syndrome and subsequent risk of Parkinson’s disease: A nationwide population-based matched-cohort study. J. Neurol. 2022;269(3):1404–1412. doi: 10.1007/s00415-021-10688-2. PubMed DOI

Alvino B., Arianna F., Assunta B., Antonio C., Emanuele D., Giorgia M., Leonardo S., Daniele S., Renato D., Buscarinu M.C., Massimiliano M., Crisafulli S.G., Aurora Z., Nicoletti G.C., Marco S., Viola B., Francesco P., Marfia A.G., Grazia S., Valentina S., Davide O., Giovanni S., Gioacchino T., Gallo A. Prevalence and predictors of bowel dysfunction in a large multiple sclerosis outpatient population: An Italian multicenter study. J. Neurol. 2022;269(3):1610–1617. [Erratum in: Prevalence and predictors of bowel dysfunction in a large multiple sclerosis outpatient population: An Italian multicenter study. J. Neurol., 2022; 269(5): 2824-2825. PubMed PMC

Lee Y.T., Hu L.Y., Shen C.C., Huang M.W., Tsai S.J., Yang A.C., Hu C.K., Perng C.L., Huang Y.S., Hung J.H. Risk of psychiatric disorders following irritable bowel syndrome: A nationwide population-based cohort study. PLoS One. 2015;10(7):e0133283. doi: 10.1371/journal.pone.0133283. PubMed DOI PMC

Meade E., Garvey M. The Role of neuro-immune interaction in chronic pain conditions; Functional somatic syndrome, neurogenic inflammation, and peripheral neuropathy. Int. J. Mol. Sci. 2022;23(15):8574. doi: 10.3390/ijms23158574. PubMed DOI PMC

Frauches B.A.C., Boesmans W. The enteric nervous system: The hub in a star network. Nat. Rev. Gastroenterol. Hepatol. 2020;17(12):717–718. doi: 10.1038/s41575-020-00377-2. PubMed DOI

Holland A.M., Frauches B.A.C., Keszthelyi D., Melotte V., Boesmans W. The enteric nervous system in gastrointestinal disease etiology. Cell. Mol. Life Sci. 2021;78(10):4713–4733. doi: 10.1007/s00018-021-03812-y. PubMed DOI PMC

Nagy N., Goldstein A.M. Enteric nervous system development: A crest cell’s journey from neural tube to colon. Semin. Cell Dev. Biol. 2017;66:94–106. doi: 10.1016/j.semcdb.2017.01.006. PubMed DOI PMC

Gershon M.D., Ratcliffe E.M. Developmental biology of the enteric nervous system: Pathogenesis of Hirschsprung’s disease and other congenital dysmotilities. Semin. Pediatr. Surg. 2004;13(4):224–235. doi: 10.1053/j.sempedsurg.2004.10.019. PubMed DOI PMC

Torroglosa A., Alves M.M., Fernández R.M., Antiñolo G., Hofstra R.M., Borrego S. Epigenetics in ENS development and Hirschsprung disease. Dev. Biol. 2016;417(2):209–216. doi: 10.1016/j.ydbio.2016.06.017. PubMed DOI

de Jonge W.J. The gut’s little brain in control of intestinal immunity. ISRN Gastroenterol. 2013;2013:1–17. doi: 10.1155/2013/630159. PubMed DOI PMC

Yang X., Lou J., Shan W., Ding J., Jin Z., Hu Y., Du Q., Liao Q., Xie R., Xu J. Pathophysiologic role of neurotransmitters in digestive diseases. Front. Physiol. 2021;12:567650. doi: 10.3389/fphys.2021.567650. PubMed DOI PMC

Spencer N.J., Travis L., Wiklendt L., Costa M., Hibberd T.J., Brookes S.J., Dinning P., Hu H., Wattchow D.A., Sorensen J. Long range synchronization within the enteric nervous system underlies propulsion along the large intestine in mice. Commun. Biol. 2021;4(1):955. doi: 10.1038/s42003-021-02485-4. PubMed DOI PMC

Annahazi A., Schemann M. The enteric nervous system: “A little brain in the gut”. Neuroforum. 2020;26(1):31–42. doi: 10.1515/nf-2019-0027. DOI

Schemann M., Frieling T., Enck P. To learn, to remember, to forget—How smart is the gut? Acta Physiol. 2020;228(1):e13296. doi: 10.1111/apha.13296. PubMed DOI PMC

Furness J.B., Clerc N., Kunze W.A. Memory in the enteric nervous system. Gut. 2000;47(S4):60–62. doi: 10.1136/gut.47.suppl_4.iv60. PubMed DOI PMC

Cheng L. Progress on the regulation of DNA methylation in the development of the enteric nervous system. Int. J. Pediatr. 2018;6:756–760.

Jaroy E.G., Acosta-Jimenez L., Hotta R., Goldstein A.M., Emblem R., Klungland A., Ougland R. “Too much guts and not enough brains”: (epi)genetic mechanisms and future therapies of Hirschsprung disease — A review. Clin. Epigenetics. 2019;11(1):135. doi: 10.1186/s13148-019-0718-x. PubMed DOI PMC

Uribe R.A. Genetic regulation of enteric nervous system development in zebrafish. Biochem. Soc. Trans. 2024;52(1):177–190. doi: 10.1042/BST20230343. PubMed DOI PMC

Kenny S.E., Tam P.K.H., Barcelo G.M. Hirschsprung’s disease. Semin. Pediatr. Surg. 2010;19(3):194–200. doi: 10.1053/j.sempedsurg.2010.03.004. PubMed DOI

Diposarosa R., Bustam N.A., Sahiratmadja E., Susanto P.S., Sribudiani Y. Literature review: Enteric nervous system development, genetic and epigenetic regulation in the etiology of Hirschsprung’s disease. Heliyon. 2021;7(6):e07308. doi: 10.1016/j.heliyon.2021.e07308. PubMed DOI PMC

Brosens E., Burns A.J., Brooks A.S., Matera I., Borrego S., Ceccherini I., Tam P.K., Barceló G.M.M., Thapar N., Benninga M.A., Hofstra R.M.W., Alves M.M. Genetics of enteric neuropathies. Dev. Biol. 2016;417(2):198–208. doi: 10.1016/j.ydbio.2016.07.008. PubMed DOI

Torroglosa A., Villalba-Benito L., Toro L.B., Fernández R.M., Antiñolo G., Borrego S. Epigenetic mechanisms in hirschsprung disease. Int. J. Mol. Sci. 2019;20(13):3123. doi: 10.3390/ijms20133123. PubMed DOI PMC

Heanue T.A., Shepherd I.T., Burns A.J. Enteric nervous system development in avian and zebrafish models. Dev. Biol. 2016;417(2):129–138. doi: 10.1016/j.ydbio.2016.05.017. PubMed DOI

Kuil L.E., Chauhan R.K., Cheng W.W., Hofstra R.M.W., Alves M.M. Zebrafish: A model organism for studying enteric nervous system development and disease. Front. Cell Dev. Biol. 2021;8:629073. doi: 10.3389/fcell.2020.629073. PubMed DOI PMC

Ganz J., Melancon E., Wilson C., Amores A., Batzel P., Strader M., Braasch I., Diba P., Kuhlman J.A., Postlethwait J.H., Eisen J.S. Epigenetic factors Dnmt1 and Uhrf1 coordinate intestinal development. Dev. Biol. 2019;455(2):473–484. doi: 10.1016/j.ydbio.2019.08.002. PubMed DOI PMC

Feng G., Sun Y. The Polycomb group gene rnf2 is essential for central and enteric neural system development in zebrafish. Front. Neurosci. 2022;16:960149. doi: 10.3389/fnins.2022.960149. PubMed DOI PMC

Liu J., Tan Y., Cheng H., Zhang D., Feng W., Peng C. Functions of gut microbiota metabolites, current status and future perspectives. Aging Dis. 2022;13(4):1106–1126. doi: 10.14336/AD.2022.0104. PubMed DOI PMC

Fujisaka S., Watanabe Y., Tobe K. The gut microbiome: A core regulator of metabolism. J. Endocrinol. 2023;256(3):e220111. doi: 10.1530/JOE-22-0111. PubMed DOI PMC

Ansari M.H.R., Saher S., Parveen R., Khan W., Khan I.A., Ahmad S. Role of gut microbiota metabolism and biotransformation on dietary natural products to human health implications with special reference to biochemoinformatics approach. J. Tradit. Complement. Med. 2023;13(2):150–160. doi: 10.1016/j.jtcme.2022.03.005. PubMed DOI PMC

Swer N.M., Venkidesh B.S., Murali T.S., Mumbrekar K.D. Gut microbiota-derived metabolites and their importance in neurological disorders. Mol. Biol. Rep. 2023;50(2):1663–1675. doi: 10.1007/s11033-022-08038-0. PubMed DOI PMC

Yeramilli V., Cheddadi R., Shah J., Brawner K., Martin C. A Review of the impact of maternal prenatal stress on offspring microbiota and metabolites. Metabolites. 2023;13(4):535. doi: 10.3390/metabo13040535. PubMed DOI PMC

Mepham J., McGee N.T., Andrews K., Gonzalez A. Exploring the effect of prenatal maternal stress on the microbiomes of mothers and infants: A systematic review. Dev. Psychobiol. 2023;65(7):e22424. doi: 10.1002/dev.22424. PubMed DOI

Yang H., Guo R., Li S., Liang F., Tian C., Zhao X., Long Y., Liu F., Jiang M., Zhang Y., Ma J., Peng M., Zhang S., Ye W., Gan Q., Zeng F., Mao S., Liang Q., Ma X., Han M., Gao F., Yang R., Zhang C., Xiao L., Qin J., Li S., Zhu C. Systematic analysis of gut microbiota in pregnant women and its correlations with individual heterogeneity. NPJ Biofilms Microbiomes. 2020;6(1):32. doi: 10.1038/s41522-020-00142-y. PubMed DOI PMC

Gorczyca K., Obuchowska A., Trojnar K.Ż., Opoka W.M., Gorzelak L.B. Changes in the gut microbiome and pathologies in pregnancy. Int. J. Environ. Res. Public Health. 2022;19(16):9961. doi: 10.3390/ijerph19169961. PubMed DOI PMC

Srinivasan K., Satyanarayana V.A., Lukose A. Maternal mental health in pregnancy and child behavior. Indian J. Psychiatry. 2011;53(4):351–361. doi: 10.4103/0019-5545.91911. PubMed DOI PMC

Tuovinen S., Pulkkinen L.M., Girchenko P., Heinonen K., Lahti J., Reynolds R.M., Hämäläinen E., Villa P.M., Kajantie E., Laivuori H., Raikkonen K. Maternal antenatal stress and mental and behavioral disorders in their children. J. Affect. Disord. 2021;278:57–65. doi: 10.1016/j.jad.2020.09.063. PubMed DOI

Van den Bergh B.R.H., van den Heuvel M.I., Lahti M., Braeken M., de Rooij S.R., Entringer S., Hoyer D., Roseboom T., Räikkönen K., King S., Schwab M. Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy. Neurosci. Biobehav. Rev. 2020;117:26–64. doi: 10.1016/j.neubiorev.2017.07.003. PubMed DOI

Sulkowska S.E.M. The impact of maternal gut microbiota during pregnancy on fetal gut-brain axis development and life-long health outcomes. Microorganisms. 2023;11(9):2199. doi: 10.3390/microorganisms11092199. PubMed DOI PMC

Rusch J.A., Layden B.T., Dugas L.R. Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis. Front. Endocrinol. 2023;14:1130689. doi: 10.3389/fendo.2023.1130689. PubMed DOI PMC

Misiak B., Łoniewski I., Marlicz W., Frydecka D., Szulc A., Rudzki L., Samochowiec J. The HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota? Prog. Neuropsychopharmacol. Biol. Psychiatry. 2020;102:109951. doi: 10.1016/j.pnpbp.2020.109951. PubMed DOI

Turroni F., Rizzo S.M., Ventura M., Bernasconi S. Cross-talk between the infant/maternal gut microbiota and the endocrine system: A promising topic of research. Microbiome Res Rep. 2022;1(2):14. doi: 10.20517/mrr.2021.14. PubMed DOI PMC

Garzoni L., Faure C., Frasch M.G. Fetal cholinergic anti-inflammatory pathway and necrotizing enterocolitis: The brain-gut connection begins in utero. Front. Integr. Nuerosci. 2013;7:57. doi: 10.3389/fnint.2013.00057. PubMed DOI PMC

Zijlmans M.A.C., Korpela K., Walraven R.J.M., de Vos W.M., de Weerth C. Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology. 2015;53:233–245. doi: 10.1016/j.psyneuen.2015.01.006. PubMed DOI

Gur T.L., Palkar A.V., Rajasekera T., Allen J., Niraula A., Godbout J., Bailey M.T. Prenatal stress disrupts social behavior, cortical neurobiology and commensal microbes in adult male offspring. Behav. Brain Res. 2019;359:886–894. doi: 10.1016/j.bbr.2018.06.025. PubMed DOI PMC

Silva Y.P., Bernardi A., Frozza R.L. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front. Endocrinol. 2020;11:25. doi: 10.3389/fendo.2020.00025. PubMed DOI PMC

Dalile B., Vervliet B., Bergonzelli G., Verbeke K., Oudenhove V.L. Colon-delivered short-chain fatty acids attenuate the cortisol response to psychosocial stress in healthy men: A randomized, placebo-controlled trial. Neuropsychopharmacology. 2020;45(13):2257–2266. doi: 10.1038/s41386-020-0732-x. PubMed DOI PMC

Zhang D., Jian Y.P., Zhang Y.N., Li Y., Gu L.T., Sun H.H., Liu M.D., Zhou H.L., Wang Y.S., Xu Z.X. Short-chain fatty acids in diseases. Cell Commun. Signal. 2023;21(1):212. doi: 10.1186/s12964-023-01219-9. PubMed DOI PMC

Chen B., Sun L., Zhang X. Integration of microbiome and epigenome to decipher the pathogenesis of autoimmune diseases. J. Autoimmun. 2017;83:31–42. doi: 10.1016/j.jaut.2017.03.009. PubMed DOI

Li L., Zhao S., Xiang T., Feng H., Ma L., Fu P. Epigenetic connection between gut microbiota-derived short-chain fatty acids and chromatin histone modification in kidney diseases. Chin. Med. J. 2022;135(14):1692–1694. doi: 10.1097/CM9.0000000000002295. PubMed DOI PMC

Stein R.A., Riber L. Epigenetic effects of short-chain fatty acids from the large intestine on host cells. Microlife. 2023;4:uqad032. PubMed PMC

Woo V., Alenghat T. Epigenetic regulation by gut microbiota. Gut Microbes. 2022;14(1):2022407. doi: 10.1080/19490976.2021.2022407. PubMed DOI PMC

Yang L.L., Millischer V., Rodin S., MacFabe D.F., Villaescusa J.C., Lavebratt C. Enteric short‐chain fatty acids promote proliferation of human neural progenitor cells. J. Neurochem. 2020;154(6):635–646. doi: 10.1111/jnc.14928. PubMed DOI

Kimura I., Miyamoto J., Kitano O.R., Watanabe K., Yamada T., Onuki M., Aoki R., Isobe Y., Kashihara D., Inoue D., Inaba A., Takamura Y., Taira S., Kumaki S., Watanabe M., Ito M., Nakagawa F., Irie J., Kakuta H., Shinohara M., Iwatsuki K., Tsujimoto G., Ohno H., Arita M., Itoh H., Hase K. Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice. Science. 2020;367(6481):eaaw8429. doi: 10.1126/science.aaw8429. PubMed DOI

Liu R.T. Childhood adversities and depression in adulthood: Current findings and future directions. Clin. Psychol. Sci. Pract. 2017;24(2):140–153. doi: 10.1111/cpsp.12190. PubMed DOI PMC

Garcia-Rizo C., Bitanihirwe B.K.Y. Implications of early life stress on fetal metabolic programming of schizophrenia: A focus on epiphenomena underlying morbidity and early mortality. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2020;101:109910. doi: 10.1016/j.pnpbp.2020.109910. PubMed DOI

Kwon E.J., Kim Y.J. What is fetal programming?: A lifetime health is under the control of in utero health. Obstet. Gynecol. Sci. 2017;60(6):506–519. doi: 10.5468/ogs.2017.60.6.506. PubMed DOI PMC

Gluckma P.D., Hanson M.A. The fetal matrix. Evolution, development and disease Cambridge. UK: Cambridge Universiy Press; 2005. Predictive adaptive responses and human disease. pp. 78–102.

Zietlow A.L., Nonnenmacher N., Reck C., Ditzen B., Müller M. Emotional stress during pregnancy - Associations with maternal anxiety disorders, infant cortisol reactivity, and mother-child interaction at pre-school age. Front. Psychol. 2019;10:2179. doi: 10.3389/fpsyg.2019.02179. PubMed DOI PMC

Howerton C.L., Bale T.L. Prenatal programing: At the intersection of maternal stress and immune activation. Horm. Behav. 2012;62(3):237–242. doi: 10.1016/j.yhbeh.2012.03.007. PubMed DOI PMC

Van den Bergh B.R.H., Van Calster B., Smits T., Van Huffel S., Lagae L. Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported depressive symptoms in adolescence: A prospective study on the fetal origins of depressed mood. Neuropsychopharmacology. 2008;33(3):536–545. doi: 10.1038/sj.npp.1301450. PubMed DOI

Begum N., Mandhare A., Tryphena K.P., Srivastava S., Shaikh M.F., Singh S.B., Khatri D.K. Epigenetics in depression and gut-brain axis: A molecular crosstalk. Front. Aging Neurosci. 2022;14:1048333. doi: 10.3389/fnagi.2022.1048333. PubMed DOI PMC

Li D., Li Y., Yang S., Lu J., Jin X., Wu M. Diet-gut microbiota-epigenetics in metabolic diseases: From mechanisms to therapeutics. Biomed. Pharmacother. 2022;153:113290. doi: 10.1016/j.biopha.2022.113290. PubMed DOI

O’Riordan K.J., Collins M.K., Moloney G.M., Knox E.G., Aburto M.R., Fülling C., Morley S.J., Clarke G., Schellekens H., Cryan J.F. Short chain fatty acids: Microbial metabolites for gut-brain axis signalling. Mol. Cell. Endocrinol. 2022;546:111572. doi: 10.1016/j.mce.2022.111572. PubMed DOI

Walker R.W., Clemente J.C., Peter I., Loos R.J.F. The prenatal gut microbiome: Are we colonized with bacteria in utero? Pediatr. Obes. 2017;2017(12 (S1)):3–17. doi: 10.1111/ijpo.12217. PubMed DOI PMC

Nuriel-Ohayon M., Neuman H., Koren O. Microbial changes during pregnancy, birth, and infancy. Front. Microbiol. 2016;7:1031. doi: 10.3389/fmicb.2016.01031. PubMed DOI PMC

Aagaard K., Ma J., Antony K.M., Ganu R., Petrosino J., Versalovic J. The placenta harbors a unique microbiome. Sci. Transl. Med. 2014;6(237):237ra65. doi: 10.1126/scitranslmed.3008599. PubMed DOI PMC

Miko E., Csaszar A., Bodis J., Kovacs K. The maternal-fetal gut microbiota axis: Physiological changes, dietary influence, and modulation possibilities. Life. 2022;12(3):424. doi: 10.3390/life12030424. PubMed DOI PMC