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Wheat Series Part 1: The Digestive Immune System

With a rapidly growing body of nutrition science covering everything from dietary proteins to microflora composition to caloric expenditure and cell bioenergetics, it’s surprising that still one of the hardest arguments to counter remains, “I’ve always eaten it and I’m fine.” It’s a point my 97-year-old grandmother likes to make every time she asks me about my research.

Let me tell you, arguing with a 97-year-old about health is not easy.

The epidemiological version of the “I’m fine” argument is an assertion we hear a lot: while evidence exists that people with celiac disease cannot eat wheat, there is no proof that consuming a gluten-free diet will benefit the rest of the population.1, 2

Celiac sufferers can’t eat wheat. We know that. But it certainly appears that most people can have their bagel, get on with their days, and be just fine—even live to see a century. So it certainly appears that the “I’m fine” argument holds up on the surface. The underlying danger, however, is that the term “fine” is so remarkably subjective.

Take the case of tennis player Novak Djokovic. He went gluten-free in 2011 and then proceeded to have the most successful season in tennis history reaching number one in the process. He was certainly fine when he was eating wheat. He was just better without it.

So let’s take the subjectivity out of fine. Since we define The Paleo Diet® as eating what we were designed to eat, perhaps a Paleo way of defining “fine” is functioning the way we were designed to function. When looked at this way, there is in fact a great deal of research showing the various ways in which wheat causes our bodies to function abnormally. A select unfortunate few, such as those with celiac disease and diabetes, may take the brunt of it, but none of us function normally eating wheat. None of us are fine.

This article is the first part in our wheat series summarizing current research on wheat and the immune system. The next few pieces will detail how wheat causes our bodies to stop functioning the way they were designed to function and can, ultimately, lead to disease. But to understand the damage, let’s start by examining what our digestive immune system looks like when it’s functioning just fine.

Digestive Immunity

Our digestive immune system is one of the most complex and robust systems in our bodies. Some 50×109 immune cells reside in the gut-associated lymphoid tissue (GALT) which makes up the bulk of our immune cells.3

But why are there so many immune cells in the gut? Because, as the image below shows, the gut is an area of constant stress. The digestive tract is continually bombarded by bacteria, food particles, and pathogens.4,5

This image is actually a highly simplified version of what goes on in the GALT. The reality is a complex mix of T Cells, monocytes, cytokines, chemokines, interleukins, adhesion molecules, and intricate processes that would have you running for a book on brain surgery to give yourself some light reading.

Don’t worry, we’re not going to cover all that.

We’re just going to focus on a few key concepts that will hopefully prove to be fascinating. But to do that we need to introduce just a few of the important players in the gut.

First is a row of tightly packed cells that keep the contents of the digestive tract from getting into the body. It is our first line of defense and normally very effective at keeping things out.6,7Leaky gut” is just a term we use for when this barrier breaks down.

Next in our line of defense are antigen presenting cells (APCs.) They are the macrophages, dendritic, and plasma cells in the image above. These cells “sample” all the food particles, bacteria, and pathogens in the gut and present them to the immune system.

The final players you need to know for this article are T Cells. They are the generals of the immune system. Antigens are presented to the T Cells and then they decide how to respond.

How the Digestive Immune System Responds to Bacteria

Generally when we think about what our immune system deals with, we think about viruses and pathogens and all those nasty things on airplanes and in our kid’s kindergarten classes.

But the truth is, dealing with a pathogen is a rare thing for our digestive immune system. Most of its energy is spent managing our microflora—those beneficial bacteria we pop probiotics and eat yogurt to encourage. We need them for our health. We just also need them to stay in our gut because they aren’t so beneficial inside our bodies.8,9,10,11

If you’re wondering how big a role these bacteria play, remember there are more cells in our microflora than cells in our own bodies. They are so important in fact that several researchers proposed that our digestive immune system evolved not because of pathogens but to allow us to live in harmony with our microflora.5,9,11,12 This is a critical distinction!

If a pathogen or even the normally healthy bacteria in our gut gets into our blood, our bodies mount an immediate and strong inflammatory response.13,14 This inflammation is what causes the aches, fevers, and chills we associate with being sick. The response to a bacterial infection in circulation, though damaging, is necessary and keeps us alive. Fortunately, bacteria rarely gets into our blood.

In the gut, on the other hand, the immune system is exposed to bacteria thousands of times each day. An inflammatory response every time would be deadly.5, 15 There’s even a name for this out of control inflammation: sepsis.16

As a result, the digestive immune system takes a very different tact with our beneficial bacteria. It becomes anergic—meaning it actually blocks inflammation.17,18 Special immune cells in the gut called T regulatory (Treg) cells and a unique type of APC cell actively shut down the inflammatory response and then quietly take out the invading bacteria one by one.3,15

When Dysbiosis Occurs

Problems arise when the bacterial infestation becomes overwhelming or when the inflammation simply doesn’t go away.5,8 As the inflammation continues, the imbalance between anti-inflammatory Treg cells and inflammatory Th17 cells builds on itself until finally the Treg cells can’t control the Th17 cells anymore.24,25,26,27 This imbalance is known as dysbiosis.

No longer protective, Th17 cells can then enter other parts of the body and contribute to a variety of chronic diseases.28,29 such as asthma,30 heart disease,31, 32 and most autoimmune conditions28,33 including celiac disease,34,35 type I diabetes,36,37 Crohn’s disease,38,39 rheumatoid arthritis,29,40 and multiple sclerosis.41

This highly pathogenic Th17 imbalance is a result of an abnormally functioning digestive immune system. Three things are known to cause it:

  1. Increased intestinal permeability (leaky gut)
  2. Chronic or too high a bacterial load
  3. Food particles that can hurt immune function

So now that you’ve plowed through all of that only-interesting-to-people-like-me immune function information, here’s the really fascinating point:

Wheat is the only food we’re aware of that causes all three.

In the remaining articles in this series, I will share with you the surprisingly large number of ways in which wheat breaks down the normal intestinal immune system and leads to damaging Th17 development and dysbiosis.42, 43 More importantly, I will show you that it happens in everyone. In other words, a normally healthy gut exposed to wheat isn’t fine in anyone.


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Trevor Connor, M.S.

Dr. Loren Cordain’s final graduate student, Trevor Connor, M.S., brings more than a decade of nutrition and physiology expertise to spearhead the new Paleo Diet team.

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