Early Life Stress in Mice Impairs Gut Immune Regulation and Leads to Worsened Future Colonic Inflammation
Published: March 15, 2023
New York, NY, March 14, 2023 – Early life stress (ELS) in mice can disrupt the gut immune response, leading to longer-lasting intestinal inflammation and a worsened future disease state than control mice not exposed to ELS, according to a new study published in Inflammatory Bowel Diseases. With support from the Crohn’s & Colitis Foundation Environmental Triggers Initiative, researchers at the University of Alabama at Birmingham found ELS can reduce colon-specific corticosterone production, altering the gut microbiome and sensitizing the intestinal immune system to future inflammatory bowel disease (IBD). The mouse model study is part of the team’s three-year research project on early life stress, which also features an ongoing clinical research study of youth with IBD (ages 11-18).
IBD, which includes Crohn’s disease and ulcerative colitis, is believed to be driven by multiple, complex interactions of genetic and environmental factors. ELS can lead to reduced hypothalamic-pituitary-adrenal (HPA) axis function and predispose to increased severity of systemic inflammatory disease. These studies outline the specific mechanisms of how early life stressors can weaken the immune system and increase disease susceptibility later in life.
In this mouse model study, researchers compared two groups of mice with IBD and exposed one group to ELS. In the ELS group, newborn mice were prematurely weaned and separated from their mothers. In the control group, the mice remained with their mothers and weaned naturally. Both groups were later chemically induced with moderate to severe colitis. Mice exposed to ELS displayed reduced plasma and colonic corticosterone (a steroid hormone that regulates the stress response in animals and known as cortisol in humans.) Additionally, the induction of colitis after ELS exposure resulted in reduced activation of glucocorticoid synthesis genes, increased levels of the proinflammatory factor TNF (Tumor Necrosis Factor), and enhanced chronicity of intestinal inflammation.
“Stress exposure during the formative years of life impairs gut immune response, which suggests those susceptible to IBD may deal with severe health consequences later in life,” said the study’s Principal Investigator, Jennifer S. Pollock, Ph.D., Professor, University of Alabama Heersik School of Medicine. “By better understanding the specific mechanisms of how early life stress impacts the gut, we hope to one day identify potential novel stress biomarkers and ultimately, treatment targets, for IBD patients who experienced early childhood adversity.”
“In 2017 we conceived and launched the Environmental Triggers Initiative focused on the understanding of how different environmental factors like psychological stress impact IBD,” said Andrés Hurtado-Lorenzo, Ph.D., VP of Translational Research & IBD Ventures at the Foundation, who leads this initiative. “I am thrilled to see that our strategic vision and investment attracted top stress researchers like Dr. Jennifer Pollock to the field of IBD and this is paying handsomely, leading to the understanding of how exposure to ELS alters IBD patients’ biology and contributing to worse disease outcomes.”
Click here to read full study in Inflammatory Bowel Diseases.
About the Crohn’s & Colitis Foundation
The Crohn's & Colitis Foundation is the leading non-profit organization focused on both research and patient support for inflammatory bowel disease (IBD), with the mission of curing Crohn's disease and ulcerative colitis, and of improving the quality of life of the millions of Americans living with IBD. The Foundation’s work is dramatically accelerating the research process through investment in research initiatives, while also providing extensive educational and support resources for patients and their families, medical professionals, and the public. For more information, visit crohnscolitisfoundation.org, call 888-694-8872, or email [email protected].
Crohn's & Colitis Foundation
The Crohn's & Colitis Foundation is a non-profit, volunteer-fueled organization dedicated to finding the cures for Crohn's disease and ulcerative colitis, and to improving the quality of life of children and adults affected by these diseases. It was founded in 1967 by Irwin M. and Suzanne Rosenthal, William D. and Shelby Modell, and Henry D. Janowitz, M.D.