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The Wheat Series Part 3: Setting Off the Bacterial Alarm Bells – With or Without the Bacteria | The Paleo Diet

Did you miss The Wheat Series Part 1: Wheat and the Immune System? Read it HERE.
Did you miss The Wheat Series Part 2: Opening the Barrier to Poor Gut Health? Read it HERE.

It’s a battle that’s been waging for millions of years. Viruses, bacteria, and a variety of pathogens looking for a nice warm home have evolved more and more sophisticated techniques to evade our immune systems. In response, our immune systems developed an array of specialized cells to launch remarkably targeted attacks at these unwanted invaders.

In the face of this cellular army, pathogens discovered one of their best weapons is a microscopic form of hide-and-seek.

Viruses mimic our bodies so immune cells pass them by.1, 2 Meningitis hangs out in the nervous system where immune cells dare not go, and HIV takes up home in immune cells themselves – after, of course, dismantling a few defenses.

These are all ways of telling the immune system “keep moving, nothing to see here.”

But what would happen if instead of looking for a good hiding place, an invader actually tried to set off the immune system alarm bells? More importantly, why would an invader want to do that?

Well, imagine you’re a plant. When some hungry animal looks at you and says “lunch” you can’t really run away. Nor can you fight back. So what do you do?

You make sure that after the animal has its meal, it is sick enough to think twice about ever touching one of your brethren.

Enter wheat.

In Part One of this series on wheat, I talked about how the normally sluggish digestive immune system can become inappropriately inflamed and lead to disease. Three things can cause this: intestinal permeability (leaky gut); chronic or too high a bacterial load; and dietary antigens.

Wheat has the unique distinction of influencing all three.

The first, intestinal permeability, is promoted by wheat through the release of zonulin.3-5 We covered that in Part Two.

Let’s get to Part Three – chronic or too high a bacterial load.

Of course, you’ve probably already realized that wheat is not bacteria. True. But the same way viruses mimic our bodies, wheat has evolved ways to “mimic” bacteria. All with the purpose of setting off the immune system alarm bells – whether the bacteria is there or not.


Our bodies actually like bacteria.

At least when they stay where they belong – in the gut.6-9 In fact, in Part One, we talked about how much of our digestive immune system evolved to allow us to live with this bacteria.7, 9-11

It’s when the bacteria – especially the less friendly types such as gram negative bacteria – get into our bodies that the immune system takes action. As a result, our immune cells have developed critical tools for the sole purpose of hunting down and identifying bacteria inside the body.

Fortunately, the bad gram negative bacteria has a tell. All over its surface is something called lipopolysaccharide (LPS).12

Antigen presenting cells (APCs) hunt down bacteria using two receptors for LPS called TLR-4 and CD14.12, 13 When LPS binds TLR-4 and CD14, the immune system alarm bells go off.

The diagram below shows the basics of this sophisticated alarm system,14 but the end result is simple. The immune system spins up and inflammation ensues.

The Wheat Series Part 3: Setting Off the Bacterial Alarm Bells – With or Without the Bacteria | The Paleo Diet


That subtitle is actually only partially accurate. A better description might be “wheat – the boy who cried bacterial wolf.”

The problem is our bodies never learn to ignore this particular boy.

Wheat has developed a variety of sophisticated techniques for activating the LPS response. But in some cases, it does it differently from LPS, bypassing key regulatory steps such as CD14 which would otherwise prevent inflammation in places we don’t want it.6, 10

A full description of these mechanisms is beyond the scope of this article and probably your boredom limit. So, the following is only a cursory description, but with lots of journal references that will keep the geekiest of you happy.


Part Two gives an in depth description of how wheat opens up the digestive tract barrier and allows things in our gut to get into our bodies. This includes our intestinal bacteria.15

The Wheat Series Part 3: Setting Off the Bacterial Alarm Bells – With or Without the Bacteria | The Paleo Diet

In other words, wheat actually lets the wolf into the chicken coop and then cries wolf.


Wheat contains its own LPS-like molecule, sometimes called LPSw, that has similar effects but admittedly isn’t as potent as the real thing.16, 17 In one study on mice, LPSw was able to promote a bacterial immune response.17


(No It’s Not a Computer Company)

At the barrier of our gut are a special type of immune cell called dendritic cells. Constantly sampling the contents of our digestive tract, tthey are the on/off switch of the immune system.18 Think of them as Paul Revere riding back to the immune system yelling “the bacteria are coming!”

Wheat contains molecules that very potently activates dendritic cells called α-Amylase/Trypsin Inhibitors (ATIs).19 They act through TLR-4 on the dendrites. And sorry to those of you who love to say you’re “gluten-free” – ATIs, which exist in many grains, are found in a different part than gluten.

ATI’s are responsible for a long known condition called Baker’s Asthma named so because it was common among people who worked with flour.20


TLR-4 and CD14 are not strongly expressed in the gut immune system making it hard to sound the bacterial alarm in the gut.21-23 In an area of the body that’s exposed to bacteria thousands of times each day, an inflammatory response isn’t something we want.21, 22

So it should be concerning to hear that wheat has developed ways of causing the inflammatory response without bothering with TLR-4 or CD14.

The ways wheat does it gets complex. We’ll just touch on them.

First, in several studies, small amounts of gluten were able to flip the dendritic cell’s “on switch” in mice and start an inflammatory response without touching TLR-4.24, 25

Another molecule in wheat (there’s a lot) called wheat germ agglutinin (WGA) can bind and pass right through the gut barrier to interact with immune cells on the other side. WGA then promotes a highly inflammatory response26, 27 including turning dendritic cells on.

Finally, remember all those antigen presenting cells in the gut that avoid sounding the bacterial alarm bells by simply not expressing CD14? Gliadin promotes something called IL-15 which is highly effective at activating APCs that don’t express CD14.28-33

And of a variety of foods tested, gliadin was the only one able to so effectively activate these cells.33


That’s a lot of science and frankly we only just skimmed the surface. So here’s the point – wheat is amazingly effective at activating the bacterial defence mechanisms of our immune cells.

More importantly, this response happens in everyone and not just celiac disease (though there’s evidence it’s more pronounced in celiacs).29

So what happens when our bodies mount a defense against bacteria that isn’t there? The answer to that question is the focus of the final part to this series. But the short answer is it creates a constant state of inflammation as long as we continue to eat wheat.34, 35

Recent research is now associating a state of constant inflammation with the onset of nearly all major chronic diseases36 including heart disease,37 Alzheimer’s disease,38 diabetes,39 cancer,40, 41 and overall morbidity.42

But the question remains does the inflammation that results from wheat inappropriately setting off the bacterial alarms also contribute to these conditions?

That’s a question we’ll hope to delve into in the next two parts. But fortunately, by eating a wheat-free Paleo diet, it’s a question you may never have to worry about.

Read The Wheat Series Part 4: Home Invasion HERE



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