Long-Term Implicit Epigenetic Stress Information (Primordial Emotions) in the Fetal Enteric Nervous System May Contribute to The Development and Maintenance of Irritable Bowel Syndrome

Author(s): Császár-Nagy N, Bókkon I.

We recently suppose that during pregnancy, stress-induced long-term implicit memory (SLEIM) might persist throughout life via the enteric nervous system (ENS) through epigenetic processes, distinct from the central nervous system (CNS). These memories could be pivotal in initiating and sustaining irritable bowel syndrome (IBS). We later improved on our original hypothesis. Specifically, prenatal stressors can alter the mother’s gut microbiota by perturbing the Hypothalamic-Pituitary-Adrenal (HPA) axis and elevating cortisol levels in the blood. Due to the ability of maternal cortisol to bypass the placental barrier, the fetus’s cortisol levels can also increase, which disrupts the HPA axis, affecting the fetus’s intestinal permeability, microbial metabolites, and gut microbiota. Epigenetic modifications induced by microbial metabolites such as short-chain fatty acids – which also influence the development and epigenetic processes of the fetal ENS – may lead to various gut-related illnesses. The bidirectional microbiota-gut-brain axis (MGBA) may convey this SLEIM information from the embryonic ENS to the CNS, resulting in the malfunctioning of emotional and pain processes. Here we assume that the fetal ENS records SLEIM during pregnancy as primordial emotional information and conveys it to the CNS via MGBA. However, fetal CNS cannot interpret these stress signals from the ENS since these are not linked to representations and can operate autonomously of the CNS. The CNS tries to manage the SLEIM signals, triggering stress response systems such as the HPA axis and the immune system, which in turn influence intestinal processes.