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Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
Published on: June 2, 2023
944
Monocyte-driven inflamm-aging reduces intestinal barrier function in females.
Candice Quin1, Jessica A Breznik2,3,4, Allison E Kennedy2,3,4
1Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, Scotland. Candice.quin@abdn.ac.uk.
Immunity & Ageing : I & A
|October 1, 2024
Summary
In humans, inflammation drives age-related gut barrier decline, not the reverse. Females show higher permeability and inflamm-aging markers, suggesting targeted barrier interventions may help but not fully prevent aging inflammation.
Area of Science:
- Gastroenterology
- Immunology
- Aging Research
Background:
- The intestinal barrier prevents harmful substances from entering the bloodstream.
- Age-related decline in barrier function may cause systemic inflammation (inflamm-aging).
- Sex differences in aging and barrier function are poorly understood.
Purpose of the Study:
- To investigate age-related changes in human intestinal barrier function.
- To explore the role of biological sex in intestinal barrier integrity and inflamm-aging.
- To determine the causal relationship between barrier function and inflamm-aging.
Main Methods:
- Analysis of sex differences in intestinal barrier markers.
- Measurement of circulating bacterial products (e.g., LPS) and inflamm-aging markers (e.g., monocytes, TNF, CRP).
- Mediation analysis to assess causality and validation in animal models.
Main Results:
- Females exhibit increased epithelial permeability and higher levels of bacterial products and inflamm-aging markers with age.
- Inflamm-aging, not impaired barrier function, precedes the increase in circulating bacterial products in humans.
- In mice, inflammation mediates the loss of intestinal barrier function, and sex influences age-associated monocyte increases.
Conclusions:
- Higher basal intestinal permeability and age-associated inflammation increase circulating LPS in females.
- Targeting intestinal barrier permeability in females may slow, but not prevent, inflamm-aging.
- Inflammation appears to be a primary driver of age-related barrier dysfunction.
