Have You Heard of Zonulin?

StickyHealth, , ,

If you have not heard of zonulin, you have most likely heard of “leaky gut”, wherein the intestine becomes over permeable to many complex molecules crossing over from the intestine into the blood stream. It is fascinating that there is an interplay between intestinal contents (microbiome and food digestates) and the immune system. There is a key which unlocks the tight junctions of the intestine, increasing its permeability, and that key is zonulin. There is a molecular pathway which regulates the amount of zonulin in concert with gut contents. Under certain conditions zonulin can be overproduced, leading to the “leaky gut”.

Zonulin has been known in the medical literature for twenty years.

Twelve years after the discovery of zonulin’s regulatory role in intestinal permeability, Alessio Fasano described how intestinal permeability can change, either way. This clear image is from his article.

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Caption for this figure. “Figure 1.Schematic representation of the zonulin mechanism of action. A. Resting state: During theresting state TJ proteins are angeged in both homophilic and heterophilic protein-proteininteractions that keep TJ in a competent state (TJ) closed as reflected by the complexity ofTJ meshwork shown in the freeze fracture electron microscopy photograph. B. Followingzonulin pathway activation: Zonulin transactivates EGFR through PAR2 (1). The proteinthen activates phospholipase C (2) that hydrolyzes phosphatidyl inositol (PPI) (3) to releaseinositol 1,4,5-tris hosphate (IP-3) and diacylglycerol (DAG) (4). PKCĪ± is then activated (5),either directly (via DAG) (4) or through the release of intracellular Ca2+ (via IP-3) (4a).Membrane-associated, activated PKCĪ± (6) catalyzes the phosphorylation of targetprotein(s), including ZO1 and myosin 1C, as well as polymerization of soluble G-actin in F-actin (7). The combination of tight junction protein phosphorylation and actinpolymerization causes the rearrangement of the filaments of actin and the subsequentdisplacement of proteins (including ZO-1) from the junctional complex (8). As a result,intestinal TJ become looser (see freeze fracture electron microscopy). Once the zonulin signaling is over, the TJ resume their baseline steady state.FasanoPage 7Clin Gastroenterol Hepatol. Author manuscript; available in PMC 2013 October 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript “

The 2020 article by Alessio Fasano linked here, describes the role of zonulin in many chronic inflammatory diseases, including autoimmune disorders, such as multiple sclerosis, metabolic disorders such as obesity, intestinal diseases, neuroinflammatory diseases such as major depressive disorder.

Recent events in my life have made knowledge of zonulin come alive for me. It is my belief that the way zonulin works is highly individual, but knowledge of it, and its workings can probably illuminate at least some of what ails each of us.

A Move

StickyExperience

About six years ago I started This Victorian Eclectic, in Galveston, and wrote over 200 posts over a a time period a little longer than than two years. Then four years ago we moved to the NW Houston suburbs, and now I am writing posts from there, where I am At Home In The Suburbs.

Streetside view of a suburban area established in the 1980’s.

The backyards are enclosed by six foot tall wooden privacy fences, which partition the light, and keep people visually separated. There are sidewalks in this neighborhood, which is a big plus for getting in walking exercise.

Covid Caught Me

Health,

Covid is ongoing, and with us to stay.

This is the second time I used an antigen test, and the first time it was positive. This iHealth test which we got in the mail, was very easy to use, and it showed a positive result within much less than 15 minutes of adding the three prepared drops into the well. I did not remotely imagine I could catch Covid, because I am twice vaccinated, and twice boosted with Moderna vaccines. We had been traveling through airports, unmasked, and intermittently were masked on planes. And I have had colds before similar to my scratchy throat, with drippy nose. But I had a cold, which was getting worse for four days, and was encouraged to take the test, which I did on the fifth day.

Soon after this test I notified my doctor, and he arranged that I get an antibody infusion, which would happen by day 7, by which time it had to occur. He explained that my medications would interfere with the oral medication, Paxlovid. I received Bebtelovimab, a monoclonal antibody which is good against the range of Covid variants including the newer ones. The team administering the antibody said that these new variants are super contagious, and I read that our vaccine- induced antibodies are not as effective against these Omicron derived variants, so I imagine I came down with a new Omicron variant. Thank goodness we have these treatments, now!

I was astonished at the very small volume of liquid containing the antibody. It appeared to be well under one milliliter. Within minutes after the antibody was put into my vein, the nurse asked me, “What is it?” It must have shown on my face that I was puzzled about a backache in my mid lower back, about the size of the palm of my hand, so I said, “I have a backache.” My nurse explained that this is a normal effect, that not very many people get, and it lasts only a minute or two. And sure enough, it was very soon gone. It is a reaction of the body to the very large protein molecule, which is what the the antibody is, he explained.

I have personally learned that Covid is more likely to catch than a cold, and I need to keep my infection guard up, with a return to liberal use of hand sanitizer. I will test more liberally, to assure that my symptoms are not Covid-related in the future, to reduce the spread. It seems likely that we will be able to get this repeatedly, as we can with colds and flu. I concur with those who predict that because the high contagion of this virus causes new mutations to arise quickly, the vaccine manufacturers are most likely to be making annual changes to the vaccine, and we will most likely be confronted with annual or semiannual vaccinations in the coming years.

Orangutan and Human Compassion

Communication, Understanding

It is truly amazing to see this non-verbal communication between two mothers of different species! Words cannot express what was captured in these photos from this article in The Daily Mail. Species do communicate! What a gift to see this!

This could happen because the glass is transparent! Transparency would help all of us understand each other. And the mothers were safe, kept apart by the glass. Safety is an essential part of transparency. Perhaps another way to say this is, there must be trust for transparency