Fecal and Circulating Biomarkers for the Non-Invasive Assessment of Intestinal Permeability

Abstract

The study of intestinal permeability is gaining growing interest due to its relevance in the onset and progression of several gastrointestinal and non-gastrointestinal diseases. Though the involvement of impaired intestinal permeability in the pathophysiology of such diseases is recognized, there is currently a need to identify non-invasive biomarkers or tools that are able to accurately detect alterations in intestinal barrier integrity. On the one hand, promising results have been reported for novel in vivo methods based on paracellular probes, i.e., methods that can directly assess paracellular permeability and, on the other hand, on fecal and circulating biomarkers able to indirectly assess epithelial barrier integrity and functionality. In this review, we aimed to summarize the current knowledge on the intestinal barrier and epithelial transport pathways and to provide an overview of the methods already available or currently under investigation for the measurement of intestinal permeability.

Keywords: intestinal barrier; intestinal permeability; non-invasive biomarkers; tight junctions.

Figure 1

Factors influencing increased intestinal permeability. Genetic susceptibility, environmental factors, dietary habits, and changes in the composition of gut microbiota can affect the intestinal barrier directly or indirectly, inducing dysbiosis that, in turn, can lead to increased intestinal permeability. The loss of intestinal barrier integrity may have a pivotal role in the onset and progression of several gastroenterologic and non-gastroenterologic diseases.

Figure 2

Intestinal barrier and passage routes across the epithelium. There are two main pathways that allow the passage of molecules through the intestinal barrier: the transcellular pathway (used by smaller hydrophilic and lipophilic solutes) and the paracellular pathway (used by larger hydrophilic solutes). Moreover, three different types of paracellular permeability are distinguished, two of which are regulated by tight junctions and are known as the pore pathway and the leak pathway. The last and third pathway is called the “unrestricted pathway”, which is independent of tight junctions and describes flux at sites of epithelial damage.