Implications on Irritable Bowel Syndrome, Fibromyalgia, Chronic Pain, and Infantile Behaviour

The enteric nervous system (ENS) can function independently of the central nervous system (CNS) in regulating complex gastrointestinal processes and may possess forms of learning and memory. Recently, we have proposed that maternal stress, depression, or anxiety during pregnancy may induce stress-related long-term epigenetic implicit memory (SLEIM) in the foetal ENS via mechanisms distinct from those of the CNS. These stress imprints may persist throughout life. Through the bidirectional microbiota–gut–brain axis (MGBA), SLEIM signals originating in the embryonic ENS may influence the CNS. Because these signals are implicit and unrelated to conscious representation, the CNS cannot directly interpret them, yet it must regulate their physiological consequences. This interaction may activate stress-response systems, including the hypothalamic–pituitary–adrenal (HPA) axis and immune pathways, leading to cortisol release, mast cell activation, and cytokine imbalance. A self-reinforcing cycle may thus develop between the ENS and CNS. The frequent comorbidity of fibromyalgia (FM) and irritable bowel syndrome (IBS) suggests shared pathogenic mechanisms, particularly central sensitization and MGBA dysfunction. Clinically, patients with FM often display childlike behavioural traits. We hypothesize that early developmental influences—potentially linked to maternal SLEIM effects on the foetal ENS—may contribute to personality immaturity in FM, similarly to IBS. Under varying biopsychosocial conditions, IBS-related mechanisms may later manifest as systemic symptoms characteristic of FM.