Saturday, 21 January 2017

How a research in cholera Vaccine, led to the discovery of the dangers of wheat.

There are many serendipitous discoveries that have happened in science. Today's post is one such story. This story is also the reason why I gave up eating wheat and I hope I have provided enough evidence for you to make an informed decision. So without much ado lets go.

Our small intestine is a place of bustling activity - the food that we eat is digested here and nutrients required for our functioning are absorbed. It is continuously supplied with blood, which in turn dissolves the nutrients that are absorbed by the intestinal wall from the food that is digested. It also has a huge flora of living microbes - some good and a few bad ones.

The intestinal wall serves two crucial functions. One, it acts as a barrier, preventing the entry of harmful substances such as foreign antigens, toxins and micro-organisms [1]. Two, it acts as a selective filter absorbing dietary nutrients, electrolytes, water and various other beneficial substances from our food (1).

These crucial functions are performed by a single layer of cells that line our intestinal wall and these cells are held together by material known as ‘Tight Junctions‘ (1).

Nutrients enter into our bloodstream either through these cells or via the closed spaces between these cells. But it is not easy for any kind of matter to pass through, in between these cells as they are sealed by “Tight Junctions” (TJ)

These tight junctions not only act as an important seal but also provides a selective transport mechanism for certain water soluble substances. While these junctions were previously believed to be static structures, new research shows that these tight junctions are dynamic which have the ability to both, control and change the size of the opening between cells! (2)

Dr. Alessio Fasano, a well renowned paediatric gastroenterologist, early in his career, was assigned the task of developing a vaccine against Cholera [an acute diarrheal disease]  at the ‘Centre for Vaccine development’ at the University of Maryland.
Vibrio cholerae, the bacteria that causes Cholera, gains entry into our bodies when we consume contaminated water or food. During his research, Dr. Fassano discovered that the Cholera microbe secreted a toxin called zonula occludens toxin (ZOT) which could open up the tight junctions between the cells of the intestine and facilitate the drawing out of water from an infected person’s bloodstream (3).

Dr. Fassano and his team, hypothesised that the cholera bacteria was mimicking a natural process in the human body and kept on working to discover this then unknown process. A year later, in 2000, Dr. Fasano discovered a natural human protein called Zonulin, which uses the same receptors as ZOT and performs similar functions (4) (5). A receptor is like a lock, all that is required to open it is a key. The cholera microbe had acquired a copy of the key Zonulin was using, to open up the TJ’s and draw water from our body.

In 2006, they made yet another fascinating discovery - Bacteria and viruses, as well as, gliadin, a key component of gluten, triggered the release of Zonulin. Zonulin was shown to increase the permeability of the intestine and allow large molecules to quietly slip through into the human blood stream (6).

In 2011, Dr. Fassano wrote a comprehensive research paper based on his years of research, in which he implicated Zonulin, to be responsible for allowing toxic molecules slip into one’s blood stream which then, could eventually lead to Inflammation, Autoimmune diseases, and Cancer (7).

Thus, to summarise, Gluten triggers the release of Zonulin in our small intestine, Zonulin then opens up the ‘Tight Junctions’ between intestinal cells and allowing all kinds of matter to pass through - From nutrients to toxins and microbes. This also means, that the more the gluten in our diet, the more the Zonulin is released, and leakier becomes our intestine. Interestingly, this process takes place in every human body regardless the person suffers from gluten intolerance or not! (8)

The only difference between a Gluten intolerant person and one without gluten intolerance is the time period that the TJ’s remain open when triggered by Zonulin. It could range from a few minutes in some to a few hours in those with celiac disease. With increased intake of wheat or maida or rava in our diet - we permit the Tight Junctions of our intestine to remain open for longer periods of time – endangering our own lives and that of our loved ones!

When we consume gluten, which is so commonly present in most of the food that we eat in the form of cakes, biscuits, bread made from wheat, barley or rye, we put ourselves at risk of developing various diseases. Perhaps, we would still remain healthy or perhaps, a few among us, may not be that fortunate, we will never know, however, being informed and putting that knowledge to use will go a long way in doing our best to care for our own health and that of our children.

There are various nutritious grains and millets that can easily replace Wheat, Rye and Barley from our diets - the question that we need to ask ourselves is, “Are we willing to make that change?”

P.S. For his work, Dr. Fassano was awarded the 2013 Linus Pauling Functional Medicine Award.

Reference :

1. Intestinal Barrier Function: Molecular Regulation and Disease Pathogenesis By Katherine R. Groschwitz, and Simon P. Hogan, PhD*. Published in the ‘Journal of Allergy and Clinical Immunology. 
2. Shen L, Weber CR, Turner JR. The tight junction protein complex undergoes rapid and continuous molecular remodeling at steady state. J Cell Biol. 2008;181:683–695. 
3. “Expression of Vibrio cholerae zonula occludens toxin and analysis of its subcellular localization.”  (Dr. Fassano’s paper from 1999)
4.  Gut October 2001;  Dr. Fassaano.
5. Journal of Cell science   Human zonulin, a potential modulator of intestinal tight junctions.
6. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.  
7. Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer. American Physiological society . 1 Jan 2011. 
8. Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity Justin Hollon Nutrients 2015. 

Diagram Sources


  1. This is a misunderstanding of Fassano's research. Only certain people are susceptible to the mechanism.

  2. Thank you for visiting our blog and sharing your thoughts and the video link with us.

    Simply to throw light on your thoughts "Only certain people are susceptible to the mechanism". Kindly refer to the citation no 8. The paper clearly states all humans are susceptible to it, not just a few. The link again (

    As far as the interview goes, Fasano states clearly that his research has been misinterpreted and names two books that he mostly disagrees with. We have not read either of those books and we do not have an opinion on them (We prefer journals and research papers because author interpretation can be misleading) .

    The issue that is dealt in our post is about Zonulin (one of Dr. Fasano's many research interest's), and it starts from 12:00 minutes of the video. Dr. Fasano states ".. indeed Zonulin increases gut permeability and give access to gluten " (rest of the part is edited out ). Then he states what we have exactly stated in our post. That it was believed the intestinal barrier was static, now they realized that it is dynamic ... etc etc.

    At around 12:50 minutes he says ; " by blocking this uncontrolled passage of these antigens (proteins that the human body reacts to), a lot of diseases can be prevented"

    Dr. Fasano in the interview says- gluten free diet was believed to be the holy grail of treating celiac disease- but it has failed because of cross contamination (the contamination is Gluten tainted food).
    So he is working towards having a safety net- that is a drug that can block zonulin receptors that could prevent a leaky gut.

    Although our post is partly based on doctor's Fasano's research, we firmly believe that a medication/ drug becomes unnecessary especially when dietary changes can achieve the same results. However when it comes to Gluten free diet, we fully agree with Dr. Fasano, that gluten free diet is indeed a fad- if ones replaces wheat with so called gluten free products which are loaded with starches, fats and sugars which too is obviously unhealthy.

    We in India are blessed with a lot of alternative grains and millets and we can lead a healthy lifestyle by substituting wheat with these. Many of them are nutritionally as good, if not better than wheat.

    We firmly believe that preventive action is better than seeking a cure.