Role of estrogen and stress on the brain-gut axis

Abstract

Symptoms of functional gastrointestinal disorders (FGIDs), including fullness, bloating, abdominal pain, and altered gastrointestinal (GI) motility, present a significant clinical problem, with a reported prevalence of 25%–40% within the general population. More than 60% of those affected seek and require healthcare, and affected individuals report a significantly decreased quality of life. FGIDs are highly correlated with episodes of acute and chronic stress and are increased in prevalence and reported severity in women compared with men. Although there is evidence that sex and stress interact to exacerbate FGID symptoms, the physiological mechanisms that mediate these sex-dependent disparities are incompletely understood, although hormonal-related differences in GI motility and visceral sensitivity have been purported to play a significant role in the etiology. In this mini review, we will discuss brain-gut axis control of GI motility and sensitivity, the influence of estrogen on GI motility and sensitivity, and stress modulation of the brain-gut axis.

Hypothalamic–vagal oxytocinergic neurocircuitry modulates gastric emptying and motility following stress

“…2014; Jiang et al . 2019 a ). It remains to be determined whether the endogenous oxytocinergic hypothalamic–vagal neurocircuit undergoes the same extent of neuroplasticity following stress load.…”

“…Rodents exposed to acute stress show dysregulation in GI motility, such as delayed gastric emptying and accelerated colonic motility (Tache & Bonaz, 2007;Zheng et al 2010;Jiang et al 2019a). Stress elevates the activity of the HPA axis, which results in the release of CRF from the PVN.…”

“…on vagal neurocircuits innervating the GI tract, was yet unclear (Zheng et al 2010;Jiang et al 2019a).…”

“…2011; Jiang et al . 2019 a ). The functions of the upper GI tract, including gastric tone and motility, are modulated by the activity of pacemaker neurones of the dorsal motor nucleus of the vagus (DMV) whose activity is regulated by a robust tonic GABAergic input from the adjacent nucleus tractus solitarius (NTS), itself the recipient of GI sensory input (Travagli and Anselmi, 2016), as well as inputs from higher centres, including oxytocin (OXT) projections that originate exclusively from the paraventricular nucleus of the hypothalamus (PVN) (Browning & Travagli, 2014).…”

“…Stress induces dysregulation of the brain-gut axis and contributes to the pathophysiology of functional gastrointestinal disorders such as functional dyspepsia and irritable bowel syndrome (Stengel & Tache, 2009;Fukudo, 2013;Drossman, 2016;Labanski et al 2020). A lack of resilience, habituation, or adaptation to stress results in an alteration in gastrointestinal (GI) motor functions, including delayed gastric emptying and accelerated colonic transit (Stengel & Tache, 2009;Khoo et al 2010;Zheng et al 2010;Babygirija et al 2011;Jiang et al 2019a). The functions of the upper GI tract, including gastric tone and motility, are modulated by the activity of pacemaker neurones of the dorsal motor nucleus of the vagus (DMV) whose activity is regulated by a robust tonic GABAergic input from the adjacent nucleus tractus solitarius (NTS), itself the recipient of GI sensory input (Travagli and Anselmi, 2016), as well as inputs from higher centres, including oxytocin (OXT) projections that originate exclusively from the paraventricular nucleus of the hypothalamus (PVN) .…”