How Metabolic Endotoxemia Is Making Your Dog Sick

Metabolic Endotoxemia In Dogs

As researchers take a closer look at how your dog’s gut impacts his health, they’ve found a surprising hidden cause of diseases …

Your dog’s immune system is activated every time he eats. This is called metabolic endotoxemia and it can be a problem for many dogs.

Let’s take a look at how your dog’s diet can cause metabolic endotoxemia … and how you can limit the after-meal inflammation that can harm his health.

The Relationship Between Your Dog And Bacteria

The power plants that drive all activity in mammals are called the mitochondria. They live inside our cells and they’re our battery packs. Mitochondria are so important they have their own DNA. And some scientists today believe mitochondria might just be bacteria.

So, mammals have a symbiotic relationship with bacteria and plants do too. Symbiotic relationships are common in nature. Just look at your dog … he gives bacteria a nice neighborhood to live in while the bacteria eat his food and stay warm and cozy. In return, many bacteria species deliver health benefits to your dog.

You probably know that beneficial bacteria species keep pathogenic bacteria populations down. But they do so much more for your dog. Bacteria can:

Diet Affects The Bacteria Living In Your Dog

Most of the bacteria that live in your dog’s gut are commensal bacteria. In Latin, commensal roughly means “to eat at the same table”. And that’s important to remember … because what you feed your dog feeds the bacteria in his gut.

The vast majority of bacteria in your dog’s gut live in his colon or large intestine. That’s because one thing commensal bacteria love to eat is fiber. 

Your dog isn’t able to digest fiber … so it passes intact through the digestive tract to the colon and feeds the commensal bacteria living there. That’s why fiber is prebiotic … it’s fermented by the bacteria that live in the colon. The probiotics then make lactic acid and SCFAs from it. 

These SCFAs are transferred to the liver for use in the body. But some SCFAs like butyrate or butyric acid stay in the gut to bolster the cells lining the gut and build mucus. This helps prevent and repair leaky gut. Butyrate can also help build immune T cells, which are essential to the immune system … and this reduces inflammation in the body.

Like plants and animals, bacteria are a diverse group of organisms. To help simplify things, scientists use taxonomy to group together bacteria with similar attributes using different categories.

One of those categories is called phyla. There are two main bacteria phyla in the gut …

  • Bacteroidetes
  • Firmicutes

Firmicutes bacteria are the most numerous in the gut, followed by Bacteroidetes. Research in dogs shows that kibble-fed dogs have a ratio of about 4:1 while raw-fed dogs have a ratio of about 3:1.

Firmicutes increase inflammation and decrease the proteins that attach the cells of the gut lining together. So, it’s important to know that diet can change the bacterial populations in your dog’s gut … and that can change his health. And both a high fat diet and a diet that’s rich in starch will grow Firmicutes populations.

Metabolic Endotoxemia And Your Dog

Researched use water-soluble dye and gram staining to identify and classify bacteria into one of two groups:

  • Gram-positive
  • Gram-negative

They’re named based on how they absorb a stain, and this is different because their cell walls are different. This is significant for your dog because the cell walls of gram-negative bacteria contain a substance called Lipopolysaccharide (LPS).

LPS protects the bacteria from harm … but it’s also an endotoxin that can harm the host. If they stay in the gut, LPS doesn’t pose any real risk to your dog. But if LPS enters the blood, it can cause real health issues, including metabolic endotoxemia. 

Healthy dogs will have small amounts of LPS circulating in their body. But the wrong diet and other environmental factors can cause the amount of LPS to increase. This is a major cause of metabolic endotoxemia … chronic inflammation from increased amounts of endotoxins in the bloodstream.

Metabolic endotoxemia affects about a third of humans … and it’s primarily a result of eating a Western diet. In fact, circulating levels of LPS are increased 5 hours after eating … and this triggers inflammation and the release of insulin.

This inflammation leads to an increased risk of …

  • Kidney disease
  • Diabetes
  • Heart disease
  • Obesity
  • Mood disorders
  • Autoimmune disorders
  • Cancer

Obviously, you want to limit the amount of LPS circulating in your dog. So, it’s important to know how it gets into your dog. To understand that, let’s take a quick look at LPS.

What Are Lipopolysaccharides (LPS)?

LPS is like a tiny suction cup … it helps gram-negative bacteria stick to the gut wall and colonize there. 

There are three key parts to LPS – its head and core are made of sugars … and it has lipid tails called lipid A.

The lipid tails are on the inside of the gram-negative bacteria’s membrane while the sugars are on the outside. If a bacterium dies, it will fall apart, as will its cell membrane … and then the LPS and its lipid A tail will be exposed and start to cause damage.

About 2/3 to 3/4 of the bacteria that live in the gut are gram-negative bacteria. This includes the Bacteroidetes phylum … although individual species of bacteria have different types of LPS.

The fatty acid tail of LPS, called lipid A, is the part of LPS that makes it an endotoxin. Lipid A can be made of one of two types of fat:

  • Saturated fats
  • Omega-3 fats

And the fatty tail determines how toxic the LPS is to your dog. If the lipid A is made of saturated fats, LPS will be toxic. But if the saturated fats in lipid A are replaced by omega-3 fats, then endotoxin toxicity will be reduced.

So now you know a bit about LPS. Next let’s talk about how it gets into your dog.

Leaky Gut In Your Dog

The most obvious way for LPS to get into the blood is leaky gut. I’m hoping by now you know what leaky gut is, but here are the very short details.

Amazingly, the only thing that stands between the contents of your dog’s gut and the rest of his body is a single layer of cells. If there’s inflammation in the gut lining, the spaces between the cells (called enterocytes) will widen. When this happens, undigested food particles can get into the blood stream, as well as toxins and viruses. And of course, LPS can leak through as well.

I think most of us think there needs to be leaky gut present for toxins to get into the blood and lymph … but LPS doesn’t necessarily need leaky gut to escape the digestive tract

When leaky gut is present and the junctions between the single layer of enterocytes are stretched, LPS can get into the bloodstream … this is called paracellular transport.

RELATED: Here’s what you need to know about leaky gut …

But in 2013, researchers found that circulating LPS increased after meals … even without leaky gut. This is because LPS can travel right through the enterocytes. This is called transcellular transport.

Cell membranes contain something called lipid rafts that allow dietary fats to travel through the cell membrane. Once the fats are inside the cell, they’re picked up by a little organelle called the Golgi apparatus. This guy packages fats up into little balls called chylomicrons, and then they get pinched out of the cell and into the lymphatic system.

But the Golgi has immune cells in it called toll-like (TL-4) receptors … and it’s here that the LPS starts to trigger an immune response and inflammation. After that it will still travel to the liver and blood, where it will cause even more damage if the liver can’t clear all of it out.

The chylomicrons that the Golgi make are little balls of protein and lipids. Their job is to transport fats out of the digestive tract, through the enterocytes, and into the lymph. The chylomicrons will then travel to the liver or get stored as fat. 

But it turns out chylomicrons really like to hold LPS as well. That means any LPS that’s not detoxified by the liver will cause low-grade inflammation along with all the diseases it causes.

So besides leaky gut … what can cause LPS to travel through the enterocyte to trigger inflammation and metabolic endotoxemia?

Factors That Increase LPS In The Bloodstream

There are many factors that increase transcellular transport of LPS.

1. Stress

Stress is a cause of metabolic endotoxemia. Research shows that stressful tasks increase LPS’s ability to stimulate the immune system.

2. Infection

If a lot of gram-negative bacteria gets into your dog’s blood, that’s a problem. This is a major cause of infection … Salmonella and E coli are both gram-negative bacteria. This also happens with periodontal disease. Bacteria from the mouth enters the blood and cause systemic inflammation.

3. Over-Feeding

High-calorie diets also increase LPS levels … even in healthy dogs. In fact, LPS levels rise consistently with the number of calories your dog eats.

RELATED: The benefits of fasting and therapeutic calorie restriction …

4. Dysbiosis

Dysbiosis (imbalanced gut bacteria) is also a major risk! Gut bacteria become imbalanced when commensal species are reduced or if some species grow out of proportion. This would happen with small intestinal bacterial overgrowth (SIBO). Remember the two main bacteria phyla in your dog’s gut are Bacteroidetes and Firmicutes. When Bacteroidetes populations decrease, the amount of blood LPS increases.

5. High-Fat Diets

High-fat diets will not only increase LPS, but free radicals. And your dog’s body fat and metabolic health will impact this. In humans, obese people have higher blood levels of LPS after eating compared to normal-weight people. And their chylomicrons contain more LPS. 

People with diabetes had the same increased elevation in LPS after meals. And high-fat, high-sugar diets will grow gram-negative bacteria species that contain LPS and cause dysbiosis. Both of these will compound the amount of LPS in the blood. In one study they fed mice a high-fat diet for 4 weeks and their LPS levels continued to increase while the control group’s LPS was only elevated after eating. 

6. Saturated Fat

This one is really interesting. Saturated fat increases LPS levels more than other fats. There are two reasons for this.

First, when lipid A has saturated fats, they activate the TL-4 receptors in the Golgi that ramp up inflammation. But if the lipid A tails contains omega-3 fats, the receptors are inhibited, and the amount of inflammation is reduced.

Second, saturated fats allow more lipid rafts to form on the enterocyte membrane … and this means more LPS will get through the enterocyte and cause metabolic endotoxemia. 

So, what are the sources of saturated fat?   

In general, ruminants are richer in saturated fat than poultry. And feeding grains will cause saturated fat levels to double. Poultry has a lower percentage of saturated fat than ruminants. But here’s the confound …

Poultry contains more fat on average, so there will still be lots of saturated fat. So, I think you should focus on a diet that’s around 10% fat … and try to limit the amount of saturated fat.

Here’s another way to do that … pay attention to your fats

  • Pork lard is 39% saturated fat
  • Palm oil is 50% saturated fat 
  • Butter is 63% saturated fat
  • Ghee is 62% saturated fat
  • Coconut oil is 80% saturated fat

A 2013 study shows that coconut oil increases permeability to LPS, which means more LPS gets through the enterocytes. Circulating LPS levels were also elevated compared to other fats.

Coconut oil also creates a more toxic form of LPS. This was recently replicated in a study on dogs.

If that wasn’t enough … coconut oil is also half lauric acid. Lauric acid is antibacterial which is generally seen as a positive, but it kills gram-negative bacteria. This releases even more LPS from their membranes. And lauric acid causes more inflammation than any other saturated fat.

So, try to balance your dog’s fats as best you can. Limit the amount to around 10% and consider stopping the coconut oil. Especially if your dog already has gut issues.

If you want the benefits of coconut oil, you can consider using MCT oil instead … but make sure it doesn’t contain lauric acid. Your dog will get the benefits of the medium chain fatty acids without the harmful effects of lauric acid.

RELATED: The ultimate guide to fats for dogs …

Probiotics Can Help

If the pathogenic bacteria in your dog’s gut get out of control, they’ll crowd out the beneficial bacteria. This can cause changes in your dog that impact his gut permeability and general health.

Beneficial bacteria secrete a SCFA called butyrate. It regulates proteins that keep the space between cells in the gut lining tight. If there’s less butyrate, these spaces will widen, and permeability will increase. That means LPS can travel into the bloodstream, along with other toxins and undesirable substances.

Probiotics are full of beneficial bacteria that colonize in your dog’s gut. And some probiotics, like Bifidobacterium and Bacillus subtilis, reduce LPS levels. One study shows Bacillus subtilis reduced LPS levels after eating a high-fat, high-calorie meal.

Putting It All Together

In a healthy dog, the cells that line his gut stay tightly together. This stops harmful substances from entering the bloodstream, including endotoxins like LPS. But sometimes the spaces between the cells widen and the contents of his gut can seep out. This is called leaky gut and experts used to believe this was the only way that LPS could travel to the bloodstream. 

But it turns out LPS can make its way to the bloodstream another way … it doesn’t need the space between cells to expand. LPS simply hitches a ride with the fats that travel through the cells lining the gut. It then makes its way into the bloodstream and the liver. Whatever your dog’s liver can’t filter will cause low-grade inflammation … and that can lead to metabolic endotoxemia and chronic disease.

Stress, infection, high-fat diets, overfeeding, dysbiosis and saturated fats … they all increase the amount of LPS that’s able to find its way out of the gut. The good news is, you can make changes to your dog’s lifestyle to reduce these risks. And that will help you prevent long-term diseases that lower your dog’s quality of life.


Mani V. Understanding intestinal lipopolysaccharide permeability and associated inflammation. Iowa State University Graduate Theses and Dissertations. 2012.

Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée A, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. American Diabetes Association. 2007 Jul;56(7):1761-72.

Fulop J. High–saturated fat diet increases endotoxemia. Natural Medicine Journal. 2018 Jul;10(6).

Lyte JM, Gabler NK, Hollis JH. The modulatory effect of common dietary fatty acids on IPEC‐J2 transport of lipopolysaccharide and monolayer barrier integrity in vitro. The Federation of American Societies for Experimental Biology. 2016 Apr 01;30(S1).

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