Have you had a heart attack? What about stroke? I'm sure you've had constipation, gas, irritable bowel syndrome, nausea, diarrhea.
I have a sensitive gut. Although I'm very particular about what I eat, I still manage to upset the tummy. We know what's good for the heart and the brain but don't pay enough attention to our gut.
In my search I came across a 2014 presentation from Dr. Alessio Fasano, founder of Center For Celiac Research. It's an hour long video but honestly it took me 3 hours going back and forth to understand the concepts and make notes. On further findings, I found that this presentation was recommended by experts like Dr. Dominic D'Agostino, PhD.
Today's newsletter is dedicated to our gut and deduced from this presentation.
Bad news: I'm not a scientist
Good news: I will not use words that you won't understand
The presentation starts with a simple question. "Why sometimes do we stay healthy and sometime we do not even when our lifestyle doesn't change?"
Till recently, the belief was that genes + environment = autoimmunity. What this meant is, that whatever you are born with and what you get exposed to results in change of health conditions.
[Autoimmunity: Sometimes the immune system makes a mistake and attacks the body's own tissues or organs. Example of an autoimmune disease is type 1 diabetes, in which the immune system destroys the cells in the pancreas that produce insulin]
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What is the gut system?
One of Dr. Alessio's 2nd grade student defined the gut as 'the intestine is a long tube with a clean open at the top and a dirty open at the bottom'.
Ofcourse, it's not as simple as food going in at the top and poop coming out at the bottom. There's complex mechanics going on in between, which is where the secrets lie.
Alright guys - things are about to get nerdy.
To make sense of science I will use a BATTLE analogy.
The intestine is the battlefield. It is here that we have friends and enemies that need to be recognised and dealt either with tolerance or with immune response. It is a highly intelligent system that decides 100's of times a day what to keep and what to kill.
Nutrients are friends, pathogens and toxins are enemies.
The entire length of the gut is a single cell layer, the fortress.
Behind the fortress are the immune cells which is our army. Alert and ready to deploy weapons when enemy is spotted.
Within the army, the dendritic cells (DC's) are the first to respond when shit hits the fan. (I was waiting to use that phrase for days!)
The army also has special forces with custom weaponry called B Cells, commonly known as antibodies.
Even more specialised are the T Cells. They produce chemicals that make the environment extremely unfriendly for any enemy (bacteria) to survive.
You guys with me so far? Good. Marching on...
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The Leaky Gut Conspiracy
The intestine is 20 feet long. The belief was that the structure of the intestine is similar to a wall of tiles perfectly lined up with cement grouting in between them. It was a group of Japanese scientists that figured out that it was less like tiles but more like doors, almost always closed. Not a wall but a door?
Have you had a heart attack? What about stroke? I'm sure you've had constipation, gas, irritable bowel syndrome, nausea, diarrhea.
I have a sensitive gut. Although I'm very particular about what I eat, I still manage to upset the tummy. We know what's good for the heart and the brain but don't pay enough attention to our gut.
In my search I came across a 2014 presentation from Dr. Alessio Fasano, founder of Center For Celiac Research. It's an hour long video but honestly it took me 3 hours going back and forth to understand the concepts and make notes. On further findings, I found that this presentation was recommended by experts like Dr. Dominic D'Agostino, PhD.
Today's newsletter is dedicated to our gut and deduced from this presentation.
Bad news: I'm not a scientist
Good news: I will not use words that you won't understand
Going back to the battlefield, think of the cells layer as a drop bridge of the fortress. Once in a while you open it to let in friends and then you close it. You definitely don't want to keep the door open all the time.
As you can imagine, if the traffic is not regulated, you can expect chemicals, bateria, virus, pollen to enter the fortress and breach our entire security system. This is what causes autoimmune diseases - asthma, Type 1 Diabetes (T1D), multiple sclerosis.
Aha! So it is not that if I have the wrong genes and am exposed to the wrong environment that can cause diseases. There also has to be a lapse in my gut security.
Ok. But, who the hell is managing this door?
It was through pure serendipity that Dr. Fasano discovered a gene called Zonulin, a potential modulator of these tight intestinal junctions.
Characteristics of Zonulin and It's signaling
Zonulin is a gene located on chromosome 16 and is associated with the following major diseases:
Autoimmune Diseases
Type 1 Diabetes, inflammatory bowel syndrome, rheumatoid arthritis, adult polycystic kidney disease
Cancers
Breast cancer, prostate cancer, leukemia, fanconi anemia, lymphoma
Nervous System
Autism, multiple sclerosis, batten's disease, lou gehrig's disease
When the intestine detects presence of unfriendlies, Zonulin gets activated.
Let's meet the enemy, shall we?
GLUTEN. A protein found in wheat, barley, rye and triticale. When humans stopped hunting for food and started cultivating it, gluten came into our lives. For 99% of our time on this planet, we have been gluten free.
The reaction observed in the intestine towards gluten is the same as in an infection. Why does the gut finds it foreign? Why does it deploy army and weapons to fight it?
Think of gluten as a long necklace that is extremely difficult to process. The gut has to first break it into pieces and then unstring each pearl and process it individually. On top of that the entire necklace is not friendly. Only certain parts can come in, we are not apt to eat this protein.
We fight with gluten all the time thinking it is bacteria.
Usually, when an unfriendly bacteria is detected, Zonulin lowers the gate, fight happens and the door closes within 20 minutes.
In the case of gluten, the gate is stuck in the open positions for hours. This is how we develop diseases.
Is this impaired intestinal barrier a cause or a symptom of diseases?
Celiac disease is an immune disorder that damages the small intestine from eating gluten. Zonulin levels and their correlation with intestinal permeability in both celiac disease and Type 1 diabetes was found to be much higher. These levels were also found to be higher in sub-groups - siblings, parents.
[permeability - measure of the ease of passage of liquids or gases or specific chemicals through a material]
Food & beverages containing gluten
Gluten foods and alternatives
Breads, cakes, pies, candies, cereals, cookies, crackers, wafers, croutons, french fries, pasta, processed meat, rice mixes, potato chips, gravies, malt, beer, salad dressings, soy sauce, soups, soup mixes
Alternate grains, starches, flour
Amarnath (rajgira), arrowroot (arbi), buckwheat (kuttu), corn, flax, millet, quinoa, tapioca, soy, sorghum (jawar for gluten free cake)
Leaky Gut Experiment In Rats
Dr. Fasano and his team did the following experiment on rats.
> breastfed for 30 days
> introduced solid foods and immediately intestine started to leak
> after 2 weeks intestine lost its barrier mechanism and the door was now open to enemy at all times
> after 2 more weeks pancreas started producing insulin
> after 2 more weeks antibodies appear, glucose level go beyond the threshold and Type 1 Diabetes has arrived
Just like humans, if you don't give insulin to this animal, it won't survive.
This was the first time a leaky gut was shown to directly influence the development of a disease.
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Moving From Animals To Humans
Scientists introduced a drop bridge regulator called Larazotide Acetate (LA). When taken along with gluten, the door did not open and the protein was simply ignored. In actuality, LA blocked Zonulin and prevented it from opening the door and letting gluten in.
Plans were underway for Phase III clinical trials of the compound when the presentation was made in 2014. I checked and it got FDA approval a few years back.
Instead of fighting the enemy, if you go gluten free there is no enemy to fight!
The War Is Upon Us
In 1972, 1 in 5000 kids in USA had Autism
In 2013, 1 in 68 kids in USA had Autism
What's driving this autoimmunity disease pandemic?
Microbiome are developed in the first three years of our birth when we play in dirt, dig our nose, scratch our butt and stick our fingers back into the mouth. This way we are training the gut to fight the enemy. With backyards almost non-existing, parents rushing to wash their kids dirty hands, the immunity has vanished. Who knew not playing in dirt could be responsible for early onset of alzheimer.
We have spent so much time studying the human genes. Our bodies have 25,000 genes. 99.5% of them are identical to chimpanzees. Only 125 genes differentiate us from them.
In comparison, we have 300,000,000,000 microbiome living inside our bodies.
Two Parallel Genomes
Human genome - inherited from both parents; stable and never changes its composition
Microbiome genome - inherited from the mother; dynamic and changes from individual to individual and within the individual from time to time
Kids born through C-section showed microbiome similar to that of their mother's skin which was exposed to whatever was in the air at the hospital at that time. Kids born through vaginal delivery showed microbiome of gut and vagina.
To improve your microbiome composition, eat more yoghurt that is a natural source of probiotics.
According to Dr. Fasano, the key to a healthy life is to live like our grandparents did. This really stuck with me. It would be fascinating to talk to 80+ year old grandmothers about what the kitchen and ingredients used to look like in their days and try to incorporate it back in our lives.
See you next Saturday. Jai Hind.
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