Note: I go much deeper in the weeds in the podcast version of this blog. I also include some pretty nifty hacks that increases blood flow to the gut. If you listen and like the podcast via itunes or any of the other podcast apps, leave me a review letting me know if you like what I’m covering or if you think I suck. It’s the best way to know if I’m investing my time wisely doing it. 🙂
People scour the internet looking for information about “leaky gut” or “leaky gut syndrome”. And while there’s a ton of information out there on supplements to take and foods to avoid, I think there’s a complete absence of background on how the gut works and how our lifestyle contributes to the problem. Enter this blog.
In my opinion, the best way to get a firm grasp on a problem is to understand the process. To do that we first need to define the problem, then identify the systems that regulate it. If we can understand how the system(s) are meant to function under optimal conditions and how they function under sub-optimal conditions, we can get a read on the proper course of action.
When most people think about “leaky gut”, what they’re really referring to is bacterial translocation. Bacterial translocation is the transfer of bacteria and bacterial components from the gut to the systemic blood circulation. As a result, there’s an activation of the immune system and persistent inflammation that can cause problems elsewhere in the body.
Now that we’ve defined our problem, let’s take a look at the gut. Specifically, how it works and how our behavior can cause bacterial translocation.
A healthy gut at the cellular level?
The gut is truly an odd organ that can best be described as a bouncer. While it functions as a barrier, it also selectively allows things located in the lumen to cross over in to the systemic circulation via the blood and lymphatic systems. Under ideal conditions, bacteria and bacterial products are kept in the lumen and never allowed access to the circulation.
This happens because bacteria are kept a safe distance away from the gut wall by a layer of mucus in the small intestine, and 2 layers of mucus in the colon. The loose mucus layer in the small intestine provides some level of protection while still allowing nutrients to be absorbed by enterocytes, the absorptive cells that form the gut wall in the small intestine.
Enterocytes form little finger-like projections called villi that increase the surface area of the gut for increased absorption capacity. Goblet cells peppered in between the enterocytes are responsible for secreting mucus and intestinal stem cells located in areas called crypts below the base of villi are responsible for replacing both cell types as they die. Paneths cells at the base of the crypts assist intestinal stem cells by secreting proteins that support them as well as anti-microbial proteins(AMPs) that take care of any bacteria that make it deep in to the mucus layer close to the intestinal wall.
In the colon, colonocytes are protected by a dense inner mucus layer and a loose outer mucus layer since they play an insignificant role in nutrient absorption and are exposed to a much larger number of bacteria, about 108x more. Keeping these guys away is more important than absorbing nutrients, but we don’t need Paneth cells because we don’t want to to kill them. They help us out quite a bit by regulating digestion, training the immune system, communicating with the brain to regulate mood and behavior, and making nutrients like vitamins K and B12.
One more function that occurs with all of these cells is the synthesis of tight junctions. Tight junctions are proteins that anchor these cells to one another, preventing unwanted particles from just crossing in between cells, a process called paracellular transport. Smaller particles such as ions can cross via this pathway, but bacteria and their toxins are kept out.
Transcellular transport is the passage of molecules through cells. Fat soluble molecules can simply pass in to enterocytes through the fatty plasma membrane. Water-soluble molecules are kept out unless they have a transporter, such as the case with water-soluble vitamins and glucose.
To enter the circulation, fats and fat soluble vitamins are organized in to lipid carrying particles called chylomicrons in enterocytes and shipped to the lymphatic system. Water soluble molecules and medium-chain and short-chain fatty acids are passed in to the portal vein which goes directly to the liver, which can detoxify anything that doesn’t belong and help distribute the good stuff to the rest of the body.
Now, it sounds like there’s a lot going on in these cells because there is. And these processes aren’t cheap, they’re quite energy intensive. In order to make enough energy to do all this “stuff”, these cells are under a high oxygen demand. They also turn over quite rapidly, which requires a lot of energy as well. Anaerobic energy metabolism simply won’t make enough ATP to do all this “stuff”.
The luminal side of these cells, where all the food is, has little to no oxygen. But the side exposed to the circulation has a rich supply of oxygenated blood from the mesenteric arteries that branch off the aorta. This is an important concept to grasp because one of the quickest, most effective ways to induce a leaky gut is by causing intestinal ischemia, a fancy way of saying, “decreasing the oxygen supply” to the gut.
When you deprive the gut of oxygen, you decrease energy supply by up to 90%. This impairs carrier-mediated transport, mucus production, AMP secretion and tight junction synthesis. You can include motility and digestive enzyme synthesis and secretion too.
Blood flow and the gut
Blood flow in the body, particularly to the gut, is a dynamic process. Blood flow to different areas of the body changes throughout the day and is regulated by the autonomic nervous system. These changes are driven, in large part, by behavior.
When we consume food, blood gets directed away from the muscles and towards the organs of digestion. This helps get oxygen to the gut when it’s ATP demand is high. Conversely, when we become physically active, blood is shunted away from our organs of digestion and distributed to the brain and muscles as the energy demand is shifted to these tissues.
This change is mediated by the interplay between the 2 branches of our autonomic nervous system: The sympathetic and parasympathetic. The sympathetic causes what is often referred to as the fight or flight response while the parasympathetic causes the rest and digest response.
In the digestive system, sympathetic activation causes the blood vessels that supply the gut to become smaller via vasoconstriction while parasympathetic activation causes them to become bigger via vasodilation. Therefore, sympathetic activation decreases blood flow to the gut while parasympathetic activation increases it. Under ideal conditions, people should be able flow between the 2 systems.
But when we become sympathetic dominant, often referred to as being stuck in fight or flight, it becomes difficult to decrease sympathetic activation and activate the parasympathetic system. This is part of the reason why stress plays such a big role in exacerbating gut conditions such as IBS.
While I think chronic stress may be a significant player in reducing blood flow to the gut, another culprit is likely a more common cause. Atherosclerosis is the accumulation of plaques on blood vessel walls. Over time these plaques reduce blood flow to areas of the body that these blood vessels serve.
While most of us associate this with heart disease and heart attacks, this process reduces blood flow throughout the body including the gut. When atherosclerosis affects blood flow to the gut, it is referred to as chronic mesenteric ischemia. Risk factors associated with this condition include:
- High lipid values(Cholesterol, LDL, Triglycerides)
Any condition that impairs blood flow to the gut will cause poor digestion by reducing the amount of oxygen available. The amount of blood reaching the gut is said to be reduced and the cells responsible for doing all the work can’t create enough energy to properly digest and absorb your food. This impacts gut motility, enzyme secretion, you name it.
Another problem is that your mucosal defense system becomes impaired leading to gut dysbiosis. And there’s not a probiotic in the world that’s going to make up for intestinal ischemia. Fortunately total ischemia is not common, but the combination of partially impaired blood flow from atherosclerosis coupled with other common behaviors may reduce blood flow to the gut to the point it causes problems. This includes chronic stress, prolonged high intensity exercise, eating too quickly, excessive heat, and endotoxemia.
Metabolic endotoxemia-Getting to leaky gut
As I mentioned above, traversing a leaky gut between cells isn’t the only way bacterial products can gain access to your circulation. Evidence indicates that it may not even be the most common way.
When we consume fat, it gets absorbed in to enterocytes. It can either be stored for later use, or taken up immediately. For absorption, it gets packaged in to chylomicrons and shipped in to the lymphatic system, which drains in to the circulation. But fat isn’t the only thing that gets absorbed this way.
A highly inflammatory component of the cell wall of gram-negative bacteria, called lipopolysaccharide or endotoxin, can also diffuse in to enterocytes and get packaged in to chylomicrons with fat. And when enough of it gains access to our circulation, it can really jack up our metabolism by causing chronic inflammation.
It’s normal for the gut to have a lot of endotoxin in it. Fortunately, we have multiple means of dealing with it. Alkaline phosphatase is an enzyme secreted in multiple tissues including the liver and gut that detoxifies endotoxin to make it inert. Adequate bile flow is also useful as it binds endotoxin, preventing absorption and increased inflammation.
But our ability to deal with endotoxin has its limits and when we exceed that capacity things can go south quickly. This is mediated by a number of behaviors. In rats, feeding a Western diet increases the absorption of endotoxin from the ileum, indicating the mucosal defense is impaired there.
A small study in humans found that eating a Western style diet(high fat) increased endotoxemia by 71% compared to a prudent-style diet(low fat), which decreased endotoxemia by 31%. This was likely due to increased transport via chylomicrons.
Physical activity also plays a role. Though intense exercise can increase endotoxin absorption while we are exercising by reducing blood flow to the gut, it also improves our ability to detoxify it. Exercise also decreases chylomicron formation. Fat gets stored in enterocytes between meals, but we metabolize that fat when we’re active, particularly during exercise. When we metabolize fat in enterocytes, it doesn’t get absorbed so it doesn’t create chylomicrons. The result…less coattails for endotoxin to ride on to sneak in to the circulation.
Habitual diet likely plays a much larger role than the content of a single meal. Over time, chronic consumption of a Western diet increases absorption of endotoxin, likely by enhanced chylomicron formation. This likely drives us to a point where we are absorbing more endotoxin than we can deal with which causes a number of alterations that can make the problem worse. It can reduce blood flow to the gut, and also to the liver, impairing our ability to detoxify it.
Another problem is that increased endotoxin impairs bile flow by decreasing the effectiveness of liver bile transporters. This would be problematic because it would remove the protective effect of bile on endotoxin absorption and inflammation. The final nail in the coffin comes as you begin experiencing chronic inflammation which leads to high blood glucose and insulin levels. I’ve mentioned numerous times how this can lead to leaky gut.
Conclusion-The perfect storm for gut destruction
Inflammation, poor bile flow, decreased circulation, and high blood glucose levels are murder to the gut. Poor circulation, inflammation, and hyperglycemia can damage the vagus nerve which is the parasympathetic branch of the autonomic nervous system. This decreases the ability of the autonomic nervous system to sense food in the gut and ramp up gut function during meals.
Fortunately we have a resident nervous system in the gut that can take care of that. Not so fortunate, the triumvirate of inflammation, decreased circulation, and high blood glucose levels does the same thing to enteric nerves that it does to the vagus nerve.
Many people feel they have “leaky gut” due to a course of antibiotics, an overseas infection, a nutrient deficiency, or a sensitivity to a certain food. Certainly these factors can play a role, but it’s important to understand how the gut works to identify a workable solution to repairing a leaky gut.
In fact, most of those issues on their own are probably not sufficient to cause a leaky gut. I’d make the argument that the proper workings of the gut would have to be disturbed before any of those things could cause a major problem. If you understand this concept, you understand how important your behavior is as a primary intervention to solving leaky gut.
8 thoughts on “Podcast 8: Solving leaky gut”
Terrific information. Are you aware of situations where the endotoxins could be resulting in high serum ammonia either by impairing the liver’s ability to process normal amounts or by causing excess production that overwhelms the liver?
I would say those things couple together, and endotoxemia may decrease blood flow to both the gut and liver. Anotehr issue could be that your small intestine is so damaged that you aren’t making enough citrulline, which helps convert ammonia in to urea.
Hey, you really suck at making bad podcast’s!! That was amazing as I applied it in my mind to inflammatory diseases and dysautonomia that have an inherent inflammatory load that destroys the gut, then you actually explained how the cycle becomes rhetorical. Thank you so much for the science. Great job.
Glad you’re getting something from the podcasts, Mark!
Hello:) my trigs are 288.. my A1c is 51 total cholesterol is 288 .. I fast every day till 22 and I do not eat much junk foid🤔🤔🤔thank you . I am 62 years old
Hey this is great info.
Feedback seeing as you asked-
You throw around a lot of scientific words and concepts and after awhile it’s overload. As you introduce lots of new things again and again. For someone that doesn’t have a biology background this is tough.
I really like when you analogies and simplify things into basic heuristics which I can easily remember.
Overall great stuff! 🙂
Thanks Fred, working on that. That’s why I try to keep the podcast under 30 minutes. Maybe I’ll start putting definitions in the written blogs to help.
Thanks for reading!
Lots of good information but for me it is overload. A summary at the end would be helpful.