Stress, sex, and the enteric nervous system

Area of Science:

• Neuroscience
• Gastroenterology
• Developmental Biology

Background:

• The enteric nervous system (ENS), comprising millions of neurons and glial cells, regulates gastrointestinal secretomotor functions and visceral pain.
• The early developmental period is critical for ENS formation and particularly vulnerable to environmental influences like stress and early life adversity (ELA).
• Emerging evidence indicates ELA impacts the brain, but the direct effects on the ENS, including changes in nerve cell number, phenotype, and reactivity, are less understood.

Purpose of the Study:

• To review the development and function of the ENS.
• To examine the influence of stress and ELA on the developing ENS, focusing on neurodevelopmental alterations.
• To discuss the role of sex in ENS susceptibility to ELA and its implications for gastrointestinal disorders.

Main Methods:

• Review of existing literature on ENS development, function, and the impact of stress and ELA.
• Analysis of findings from studies, including recent work in pigs, a relevant mammalian model.
• Discussion of sex-specific differences in ENS response to ELA.

Main Results:

• The ENS is directly affected by ELA, with observed changes in enteric nerve populations.
• Studies in pigs confirm that ELA can induce alterations in the ENS, mirroring findings in smaller mammals.
• Significant sex-differential susceptibility of the ENS to ELA was identified, suggesting a basis for higher GI disorder prevalence in females.

Conclusions:

• Early life adversity can lead to lasting neurodevelopmental changes in the enteric nervous system.
• Sex is a critical factor influencing the ENS's vulnerability to early life stress.
• Understanding these sex-specific effects is crucial for addressing the higher prevalence of gastrointestinal disorders in women.