Medical Leaky gut and autoimmune diseases

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The discussion centers on the hygiene hypothesis of autoimmunity and its implications, particularly regarding the role of impaired intestinal barrier function in autoimmune diseases. Autoimmune disorders result from immune responses targeting specific organs, and the intestinal epithelial barrier plays a crucial role in maintaining the balance between tolerance and immunity to non-self antigens. Zonulin is identified as a key modulator of intercellular tight junctions, influencing the trafficking of macromolecules and the immune response. When the zonulin pathway is disrupted in genetically predisposed individuals, it can lead to autoimmune conditions. This emerging paradigm challenges traditional theories and suggests that restoring zonulin-dependent intestinal barrier function may prevent or treat autoimmune diseases. Evidence from animal studies and clinical research supports this view, highlighting the need for innovative therapeutic approaches. The conversation also notes the significance of synthesis papers in summarizing diverse research and their role in advancing understanding, while acknowledging that such works should be critically evaluated.
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This is looking to fit quite well with the hygiene hypothesis of autoimmunity, and the implications are ridiculously enormous. What do you think?

Abstract - Autoimmune diseases are characterized by tissue
damage and loss of function due to an immune response that is
directed against specific organs. This review is focused on the
role of impaired intestinal barrier function on autoimmune
pathogenesis. Together with the gut-associated lymphoid
tissue and the neuroendocrine network, the intestinal epithelial
barrier, with its intercellular tight junctions, controls the
equilibrium between tolerance and immunity to non-self
antigens. Zonulin is the only physiologic modulator of
intercellular tight junctions described so far that is involved
in trafficking of macromolecules and, therefore, in tolerance/
immune response balance. When the zonulin pathway is
deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts
traditional theories underlying the development of these
diseases and suggests that these processes can be arrested if
the interplay between genes and environmental triggers is
prevented by re-establishing the zonulin-dependent intestinal
barrier function. Both animal models and recent clinical
evidence support this new paradigm and provide the rationale
for innovative approaches to prevent and treat autoimmune
diseases.

http://www.celiaccenter.org/documents/publications/Leaky%20gut%20and%20autoimmune%20diseases,%20Clinical%20Reviews%20in%20Allergy%20&%20Immunology,%20November%202011.pdf
 
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These types of papers are usually published in journals that specialize in reviews. Reviews are papers that summarize research and try to make sense of it.

The folks interested celiac disease and Type I diabetes research have known about zonulin controlling the gut "sieve" size for a while now. They are starting to run with it.
http://www.ncbi.nlm.nih.gov/pubmed/16644703.

Celiac patients have increased levels of zonulin in their gut, for example, compared with non-celiac controls.

This paper is a synthesis piece. They are taking research from seveeal areas and trying to synthesize an overall viewpoint. This is analogous to what the Physics community is trying to do with the many proposed models to bring all of Physics together. Think of the paper as proposing a model, one that can and should be tested extensively.

Here is another paper like your link:
http://physrev.physiology.org/content/91/1/151.long

It has a nice review of literature and a good explanation of what is currently known.
But you will notice the word "cancer" in the title. So again this is a synthesis piece. And is speculative.

We need articles like these. They have a useful function. But we do not have to buy what they are selling.
 
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