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.

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Graphical abstract

Fig. 1.

The effect of estrogen or stress in the brain-gut axis. The brain-gut axis, illustrated on the left, comprises bidirectional communication from the visceral organs to the brain via spinal and parasympathetic connections. Within the stress and pain responsive areas in the brain, such as the amygdala (AMY), cingulate cortex (CING), hippocampus (HIP), and hypothalamus (HYPO), integrate signals from the gastrointestinal (GI) tract are transmitted through brainstem areas such as the dorsal vagal complex (DVC). The bidirectional communication is relayed and modified within parasympathetic ganglia, such as the nodose ganglia (NG), and/or sympathetic dorsal root ganglia (DRG), with further regulation of noxious signals within the dorsal horn of the spinal cord. Within the GI tract, the stomach and small intestine (Sm. Intest.) are primarily innervated by vagal afferents, whereas the majority of the large intestine (Lg. Intest.) is innervated by spinal afferents. For each region of the brain-gut axis, the summarized effect of estrogen signaling or stress on sensation (sen) or motility (mot) is indicated with up arrows (↑) for increased responses, down arrows (↓) for decreased responses, or both arrows (↑↓) when the response can both increase and decrease depending on the receptor subtype. Changes are measured compared with ovariectomized females for estrogen or nonstressed baselines for stress. A “−” indicates that there is no literature consensus on the effect at the listed region. Brain and GI images modified from CNX OpenStax/Wikimedia Commons/CC-BY-4.0. Available at https://commons.wikimedia.org/wiki/File:Figure_35_03_06.jpg and https://commons.wikimedia.org/wiki/File:GI_normal.jpg.