The Intestinal Barrier Dysfunction as Driving Factor of Inflammaging

Abstract

The intestinal barrier, composed of the luminal microbiota, the mucus layer, and the physical barrier consisting of epithelial cells and immune cells, the latter residing underneath and within the epithelial cells, plays a special role in health and disease. While there is growing knowledge on the changes to the different layers associated with disease development, the barrier function also plays an important role during aging. Besides changes in the composition and function of cellular junctions, the entire gastrointestinal physiology contributes to essential age-related changes. This is also reflected by substantial differences in the microbial composition throughout the life span. Even though it remains difficult to define physiological age-related changes and to distinguish them from early signs of pathologies, studies in centenarians provide insights into the intestinal barrier features associated with longevity. The knowledge reviewed in this narrative review article might contribute to the definition of strategies to prevent the development of diseases in the elderly. Thus, targeted interventions to improve overall barrier function will be important disease prevention strategies for healthy aging in the future.

Telomere dysfunction impairs intestinal differentiation and predisposes to diet-induced colitis

“…It remains to be established whether the shorter telomeres in the neoblastic adenomas is accompanied by differentiation and barrier defect. Establishing the role of short telomeres in human intestinal aging is important, given the growing body of evidence that an altered microbiome and barrier dysfunction are important factors for local and systemic aging decline and disease 15,31,87 .…”

“…Besides barrier dysfunction, malabsorption is another important clinical consequence of patients with IE defects that can lead to systemic deficiencies of nutrients as well as an increased spillover of nutrients into the colon where it can impact microbiome composition and metabolism 14 . These human studies are supported by a large body of animal studies that indicate the importance of intestinal barrier as a regulator of intestinal and systemic inflammation and predictor of age-onset mortality 15 . However, a major challenge in this rapidly evolving field is our poor understanding of the underlying factors that drive barrier dysfunction.…”

The role of the gut microbiota in health and cardiovascular diseases

“…One of the most important functions of the gut microbiota is establishing the normal intestinal mucosal barrier with other components in the host intestine [ 46 ]. The intestinal mucosal barrier is mainly composed of the intestinal epithelial cell junction complex and its secretions, immune cells, and gut microbiota [ 47 ]. The complete intestinal mucosal barrier can effectively block the colonization and invasion of pathobionts and maintain the stability of the intestinal environment [ 48 , 49 ].…”

Probing the leak pathway: Live‐cell imaging of macromolecule passage through epithelia

“…Excessive passage of such putatively antigenic material across epithelial barriers is of great interest as increasing evidence suggests that it may be at the bottom of a variety of diseases. [10][11][12] But the molecular and biophysical basis of the leak pathway is still unclear and different models are being discussed. 13 For example, the dynamic strand and dynamic membrane apposition models 7,14 both assume a dynamic breaking and reorganization of the cell junctions and/or the TJ strands.…”