Research Topic

The Role of Physical and Biological Gut Barriers in Modulating Crosstalk between the Microbiota and the Immune System

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The intestine has several means for maintaining immune homeostasis and for avoiding inflammation despite massive antigenic stimulation by food components and by commensal bacteria residing in the gut mucosa. These mechanisms include physical and biological barriers such as (i) the intestinal epithelial ...

The intestine has several means for maintaining immune homeostasis and for avoiding inflammation despite massive antigenic stimulation by food components and by commensal bacteria residing in the gut mucosa. These mechanisms include physical and biological barriers such as (i) the intestinal epithelial barrier (IEB); (ii) the gut vascular barrier (GVB) and (iii) the mucus layer. In particular, the mucus layer does not simply act as a diffusion barrier but has important dynamic functions that regulate the type of commensal bacteria residing in the inner mucus layer, enabling the passage of food and bacterial products into the gut tissue and systemic circulation. Importantly, the mucosal layer also has key immune regulatory functions. A healthy mucus structure is fundamental for promoting the presence of beneficial commensal bacteria, such as the short-chain fatty acids (SCFA)-producing bacteria which are known to promote immune tolerance. Moreover, the mucus layer contains anti-microbial peptides (AMPs) and mucins that have key immune modulatory functions. The integrated response of these combined defense systems is fundamental for containing microbes and their products within the intestine; for avoiding their systemic spread and for suppressing their capacity to activate systemic immune and autoimmune responses.

Recent lines of evidence indicate that damage to gut barrier integrity is present not only in intestinal inflammatory diseases, but also in extra-intestinal autoimmune diseases and in chronic liver inflammatory conditions. These findings suggest that gut barriers are fundamental for preventing bacterial translocation and for avoiding the pathological activation of the immune system that can result in chronic inflammation and autoimmunity.

In this Research Topic, we aim to assemble a series of articles that highlight how the structure and biological functions of the physical and biological gut barriers are crucial for modulating of the immune system at the intestinal level and systemically, in both homeostasis and disease. We aim to collect studies that report pathological conditions in which the loss of gut barrier integrity is associated with alterations in gut and systemic immune homeostasis. We also aim to collect novel findings on the possible mechanisms through which leakage of the gut barrier and the loss/absence of its essential immune regulatory functions lead to chronic inflammatory and autoimmune diseases (e.g., abnormal interaction between commensal microbiota and the immune system; translocation of bacterial products into peripheral organs, etc.). We welcome the submission of Review, Mini-Review and Original Research articles that cover, but are not limited to, the following topics:

1. The role of the structure and biological functions of the intestinal epithelial barrier, the gut vascular barrier and the mucus layer in regulating immunity.
2. Dysbiosis, gut inflammation and leakage of the gut barrier.
3. Immuno-pathological conditions in mice and humans associated with breakage / disruption of gut barrier integrity.
4. Abnormal crosstalk between the commensal microbiota and the immune system in the gut: translocation of bacterial products and mechanisms of immune activation.
5. Dietary and therapeutic interventions aimed at restoring gut barrier integrity and gut immune homeostasis.


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