The relationship between dysbiosis and central nervous diseases has been proved in
the last 10 years. Microbial alterations cause increased intestinal permeability,
and the penetration of bacterial fragment and toxins induces local and systemic inflammatory
processes, affecting distant organs, including the brain. Therefore, the integrity
of the intestinal epithelial barrier plays a central role in the microbiota–gut–brain
axis. In this review, we discuss recent findings on zonulin, an important tight junction
regulator of intestinal epithelial cells, which is assumed to play a key role in maintaining
of the blood–brain barrier function. In addition to focusing on the effect of microbiome
on intestinal zonulin release, we also summarize potential pharmaceutical approaches
to modulate zonulin-associated pathways with larazotide acetate and other zonulin
receptor agonists or antagonists. The present review also addresses the emerging issues,
including the use of misleading nomenclature or the unsolved questions about the exact
protein sequence of zonulin.
