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.

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.

What goes around comes around: novel pharmacological targets in the gut-brain axis.

The gut and the brain communicate bidirectionally through anatomic and humoral pathways, establishing what is known as the gut-brain axis. Therefore, interventions affecting one system will impact on the other, giving the opportunity to investigate and develop future therapeutic strategies that target both systems. Alterations in the gut-brain axis may arise as a consequence of changes in microbiota composition (dysbiosis), modifications in intestinal barrier function, impairment of enteric nervous system, unbalanced local immune response and exaggerated responses to stress, to mention a few. In this review we analyze and discuss several novel pharmacological targets within the gut-brain axis, with potential applications to improve intestinal and mental health.

Short-term effects of Poly(I:C) on gut permeability.

The intestinal barrier function depends on an adequate response to pathogens by the epithelium. Toll-like receptor 3 (TLR-3) recognizes double-stranded RNA, a virus-associated molecular pattern. Activation of TLR-3 with Poly(I:C), a synthetic agonist, modulates tissue repair and permeability in other epithelia; however, the effects of local luminal TLR-3 agonists on gut barrier function are unknown. The aim of this investigation was to evaluate short-term effects of Poly(I:C) on rat ileal and colonic permeability ex vivo. We also studied the acute effects of intrarectal administration of Poly(I:C) on colonic barrier function. Ileum tissues displayed decreased transepithelial electrical resistance (TEER) 1h after incubation with 200µg/mL Poly(I:C); however, the mucosa-to-serosa transit of macromolecules (4.4 and 40kDa dextrans - TD4.4 and FD40, respectively) remained unchanged. Conversely, colon tissue preparations stimulated with 200µg/mL Poly(I:C) showed a decreased thinning of the mucosal layer after 2h and a decreased transit of FD40 after 3h, in comparison to controls. There was no change in colonic TEER after 3h of treatment. In addition, colon tissue taken from rats 6h after an intrarectal administration of 100µg Poly(I:C) also showed decreased permeability to FD40 in the everted gut sac assay at 3h post-extraction. Tissue morphology remained unchanged. Our results suggest that an acute exposure to Poly(I:C) reduces colon permeability to macromolecules but increases ileum permeability to electrolytes/small molecules ex vivo. Although the mechanism associated to these effects needs further investigation, to our knowledge this is the first report of a direct effect of a TLR-3 ligand in intestinal barrier function and may be of significance to understand region-specific interactions between gut mucosa and microbiota.