Unpopular opinion on trendy gut health peptides I believe zonulin-mediated increases in intestinal permeability is an evolutionary adaptation (of course it is). By opening tight junctions, zonulin regulates flux of water, solutes, and immune cells. But why does small-intestinal exposure to both bacteria trigger luminal zonulin release, followed by tight junction disassembly and increased permeability? WHY? This transient opening could potentially flush out bacteria and their products from the proximal small intestine, limiting persistent colonization in a region that normally has low bacterial loads (SIBO is not normal remember). Zonulin is part of the innate defence program. It senses microbes, rapidly loosens junctions, and promotes fluid and antigen movement to prevent overgrowth and facilitate immune surveillance. Tight junction modulation also supports controlled antigen sampling, leukocyte movement, and mucosal immune education, which are essential for immune tolerance. This is an adaptive response! Where does it go wrong? Chronic or exaggerated zonulin activation is associated with celiac disease, type 1 diabetes, IBD, and other chronic inflammatory and autoimmune conditions, where sustained barrier loosening amplifies antigen influx and immune activation. Modern triggers lead to a maladaptive chronic and exaggerated activation of this process. So what about peptides like Larazotide acetate? This peptide inhibits zonulin signaling at tight junctions. Sound promising for those with celiac disease, and other leaky-gut conditions. But my point with this post is, do you, as a healthy individual want to chronically inhibit zonulin signalling? Probably not. So this is a great tool to use, in the right CONTEXT. Not for everyone all the time.
