{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:36:57Z","timestamp":1786451817413,"version":"build-2736575974"},"reference-count":122,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The enteric nervous system (ENS) can function semi-autonomously from the central nervous system (CNS) in regulating complex gastrointestinal processes and exhibits substantial developmental, epigenetic, neuroimmune, and adaptive plasticity. We propose the concept of Stress-Induced Long-term Epigenetic Implicit Memory (SLEIM) as a hypothesis-generating theoretical framework suggesting that prenatal maternal stress may contribute to persistent biological alterations within ENS-related pathways through interacting epigenetic, neuroimmune, neuronal, glial, and microbiota-associated mechanisms. The precise biological substrates and mechanisms underlying this proposed framework remain unknown. Through the microbiota\u2013gut\u2013brain axis (MGBA), such stress-related biological alterations may influence physiological communication between the ENS and CNS and in turn affect stress-response systems, including HPA axis activity, immune signalling, cortisol regulation, mast-cell activation, and cytokine balance. The frequent comorbidity of fibromyalgia (FM) and irritable bowel syndrome (IBS) suggests the existence of shared pathogenic mechanisms involving central sensitisation, neuroimmune processes, and MGBA dysfunction. In this study, we therefore also address dependency-related characteristics and autonomy vulnerabilities reported in some patients with FM and consider how developmental, psychological, neurobiological, and illness-related factors may contribute to these patterns. Within the proposed SLEIM framework, prenatal stress-related biological influences may represent a potential developmental pathway that contributes to vulnerability to IBS, FM, and related functional disorders later in life. However, these relationships remain hypothetical and require future empirical investigation.<\/jats:p>","DOI":"10.3390\/ijms27167177","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:51:36Z","timestamp":1786449096000},"page":"7177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal Stress, Enteric Nervous System Development, and the Microbiota\u2013Gut\u2013Brain Axis: A Hypothesis-Generating Framework for Irritable Bowel Syndrome and Fibromyalgia"],"prefix":"10.3390","volume":"27","author":[{"given":"Noemi","family":"Cs\u00e1sz\u00e1r-Nagy","sequence":"first","affiliation":[{"name":"Faculty of Public Governance and International Studies, Ludovika University of Public Services, H-1083 Budapest, Hungary"},{"name":"Psychosomatic Outpatient Clinics, H-1037 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"B\u00f3kkon","sequence":"additional","affiliation":[{"name":"Psychosomatic Outpatient Clinics, H-1037 Budapest, Hungary"},{"name":"Neuroscience and Consciousness Research Department, Vision Research Institute, Inc., Lowell, MA 01854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.2174\/1570159X22666240507095700","article-title":"Long-Term Implicit Epigenetic Stress Information in the Enteric Nervous System and its Contribution to Developing and Perpetuating IBS","volume":"22","author":"Bob","year":"2024","journal-title":"Curr. 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