Gut Susceptibility to Viral Invasion: Contributing Roles of Diet, Microbiota and Enteric Nervous System to Mucosal Barrier Preservation.

The gastrointestinal lumen is a rich source of eukaryotic and prokaryotic viruses which, together with bacteria, fungi and other microorganisms comprise the gut microbiota. Pathogenic viruses inhabiting this niche have the potential to induce local as well as systemic complications; among them, the viral ability to disrupt the mucosal barrier is one mechanism associated with the promotion of diarrhea and tissue invasion. This review gathers recent evidence showing the contributing effects of diet, gut microbiota and the enteric nervous system to either support or impair the mucosal barrier in the context of viral attack.

Sertraline and Citalopram Actions on Gut Barrier Function.

INTRODUCTION: Disruption of intestinal barrier is a key component to various diseases. Whether barrier dysfunction is the cause or effect in these situations is still unknown, although it is believed that translocation of luminal content may initiate gastrointestinal or systemic inflammatory disorders. Since trauma- or infection-driven epithelial permeability depends on Toll-like receptor (TLR) activity, inhibition of TLR signaling has been proposed as a strategy to protect intestinal barrier integrity after infection or other pathological conditions. Recently, selective serotonin recapture inhibitors including sertraline and citalopram were shown to inhibit TLR-3 activity, but the direct effects of these antidepressant drugs on the gut mucosa barrier remain largely unexplored. MATERIALS AND METHODS: To investigate this, two approaches were used: first, ex vivo studies were performed to evaluate sertraline and citalopram-driven changes in permeability in isolated intestinal tissue. Second, both compounds were tested for their preventive effects in a rat model of disrupted gut barrier, induced by a low protein (LP) diet. RESULTS: Only sertraline was able to increase transepithelial electrical resistance in the rat colon both when used in an ex vivo (0.8 µg/mL, 180 min) or in vivo (30 mg/kg p.o., 20 days) fashion. However, citalopram (20 mg/kg p.o., 20 days), but not sertraline, prevented the increase in phospho-IRF3 protein, a marker of TLR-3 activation, in LP-rat ileum. Neither antidepressant affected locomotion, anxiety-like behaviours or stress-induced defecation. CONCLUSION: Our data provides evidence to support the investigation of sertraline as therapeutic strategy to protect intestinal barrier function under life-threatening situations or chronic conditions associated with gut epithelial disruption.

Investigating Gut Permeability in Animal Models of Disease.

A growing number of investigations report the association between gut permeability and intestinal or extra-intestinal disorders under the basis that translocation of gut luminal contents could affect tissue function, either directly or indirectly. Still, in many cases it is unknown whether disruption of the gut barrier is a causative agent or a consequence of these conditions. Adequate experimental models are therefore required to further understand the pathophysiology of health disorders associated to gut barrier disruption and to develop and test pharmacological treatments. Here, we review the current animal models that display enhanced intestinal permeability, and discuss (1) their suitability to address mechanistic questions, such as the association between gut barrier alterations and disease and (2) their validity to test potential treatments for pathologies that are characterized by enhanced intestinal permeability.

Protein Malnutrition During Juvenile Age Increases Ileal and Colonic Permeability in Rats.

Protein malnutrition can lead to morphological and functional changes in jejunum and ileum, affecting permeability to luminal contents. Regarding the large intestine, data are scarce, especially at juvenile age. We investigated whether low-protein (LP) diet could modify ileal and colonic permeability and epithelial morphology in young rats. Isocaloric diets containing 26% (control diet) or 4% protein were given to male rats between postnatal days 40 and 60. LP-diet animals failed to gain weight and displayed decreased plasma zinc levels (a marker of micronutrient deficiency). In addition, transepithelial electrical resistance and occludin expression were reduced in their ileum and colon, indicating increased gut permeability. Macromolecule transit was not modified. Finally, LP diet induced shortening of colonic crypts without affecting muscle thickness. These data show that protein malnutrition increases not only ileum but also colon permeability in juvenile rats. Enhanced exposure to colonic luminal entities may be an additional component in the pathophysiology of protein malnutrition.