Metabolic Endotoxemia: One Root Cause of Many Diseases of Affluence

Adapted from episode 93 of The Perfect Stool podcast with your host, Lindsey Parsons, EdD, gut health coach.

Metabolic Endotoxemia

Today I’m going to be talking about a topic that may be unfamiliar but deeply connected with a lot of gut issues, which causes chronic inflammation and contributes to numerous other chronic health conditions common in the developed world and that’s metabolic endotoxemia.

What is metabolic endotoxemia?

So, you may have heard that bacteria are divided into two groups, gram-positive and gram-negative. Gram-negative bacteria are surrounded by an outer membrane containing something called lipopolysaccharide or LPS. Gram-positive bacteria lack an outer membrane. And when you stain them when looking under a microscope, they look different than gram-negative ones. So you may know that the two primary phyla of bacteria in the human gut are Firmicutes, which are gram positive, and Bacteroidetes, which are gram negative. Then the next two largest phyla are proteobacteria, which are gram-negative and actinobacteria, which are gram positive. Most of the major bacterial gut pathogens that you’ve heard of are gram negative proteobacteria, like salmonella, E coli (although most types of E coli are not pathogenic) and camphylobacter. Probably logically because they are facultative anaerobes, so they can live in the presence of oxygen, hence are easy to pass between people and make you sick.

So endotoxins are toxins in the bacterial cell wall of gram negative bacteria, which are released when the cell disintegrates upon death and also released in much smaller amounts when they’re alive. And this endotoxin is composed mainly of LPS, which activates the inflammatory response. So even small amounts of LPS in the blood from a bacterial infection can elicit an inflammatory response and trigger the release of inflammatory cytokines or chemical messengers, which leads to low-grade chronic inflammation.

So to put it all together, metabolic endotoxemia is a diet-induced 2-3 fold increase in plasma LPS levels. And if it happens after eating, it’s called post-prandial metabolic endotoxemia. So in other words, you eat a meal, and mostly dead bacterial body parts start escaping out of your gut and sparking off inflammation.

So as you may be guessing, something that goes hand and hand with metabolic endotoxemia is intestinal permeability, aka leaky gut. I did an entire episode on leaky gut, which is episode 24, from March of 2020, so you can listen to that to get the lowdown, but to summarize briefly, leaky gut can come from an overgrowth of the very proteobacteria that you don’t want escaping out of your gut, as in SIBO (small intestine bacterial overgrowth), from certain foods that contain lectins, added sugar, alcohol, nutrient deficiencies, chronic stress, smoking, toxin overload and dysbiosis. So there’s lots of ways you can end up with a leaky gut.

What conditions are associated with metabolic endotoxemia?

The consequences of metabolic endotoxemia are many. Symptoms and diseases associated with it include insulin resistance, obesity, type 2 diabetes, non-alcoholic fatty liver disease, chronic kidney disease, atherosclerosis, chronic constipation, low testosterone, chronic pain, cognitive decline, memory loss, appetite disorders, depression and anxiety. It can also promote autoimmunity and suppress the activity of your thyroid and cause autoimmune thyroid disease, which is Hashimoto’s thyroiditis, if you’re hypothyroid and Grave’s disease if you’re hyperthyroid. Endotoxemia also plays a role in Chronic Fatigue Syndrome and is associated with markers seen in early Parkinson’s disease patients.

So there are a number of causes beyond just a leaky gut for metabolic endotoxemia, and many of these causes also cause the gut to be leaky, so it’s all intermingled as you will see. The first is a high fat diet, but in studies but these were typically high junk food diets as well, so I don’t think we can assume that this applies to a carefully constructed ketogenic diet, for example. Fructose consumption is another cause, but this is referring to high fructose corn syrup and other fructose added to foods, and consumed in high quantities in the absence of fiber and nutrients found in fruit.  

SIBO is another cause of metabolic endotoxemia. It turns out that the primary bacteria in people with a positive hydrogen breath test, which is a diagnostic tool for SIBO, are Enterobacteriaceae, which are gram negative. The most common specific overgrown bacteria found in SIBO include Escherichia coli (gram negative), Enterococcus spp. (gram positive), Klebsiella pneumoniae (gram negative) and Proteus mirabilis (gram-negative). So the majority are gram negative and produce LPS, and just having an overabundance of those gram negative proteobacteria will itself cause leaky gut and then these are the bacteria with LPS.  

Chronic alcohol consumption can also be a cause. This happens because alcohol can increase pathogenic bacteria and decrease beneficial bacteria. Also, the metabolism of alcohol generates reactive oxygen species (also known as oxidative stress), which can damage gut cells and impair gut barrier function, allowing for the translocation of LPS into the bloodstream.

Periodontal disease is another possible cause, because in periodontal disease you have an overgrowth of harmful bacteria in the oral microbiome, which of course leads into the gut microbiome, and can cause dysbiosis and intestinal permeability and the leakage of LPS. And the primary pathogens in periodontal disease are also gram negative.

This one doesn’t seem fair, but aging itself can lead to metabolic endotoxemia, because it’s known that as we age our gut diversity decreases, which can then contribute to an imbalance in the gut microbiota and promote the growth of pathogenic bacteria that produce endotoxins. Aging is also associated with an increase in intestinal permeability, which may be due in part to age-related changes in gut physiology, such as decreased gut motility. In addition, aging is associated with a decline in organ function, including the liver and kidneys, which are important for detoxification and elimination of bacterial toxins. Impaired liver and kidney function can lead to an accumulation of bacterial toxins, contributing to metabolic endotoxemia.

And finally, smoking causes metabolic endotoxemia in the same way that alcohol use does, by creating dysbiosis and oxidative stress, which damage the gut barrier and create intestinal permeability, and by impairing liver function, which can lead to a decrease in the clearance of LPS from the bloodstream, contributing to metabolic endotoxemia.

How do I stop metabolic endotoxemia?

If you’re having lots of bloating, gas or acid reflux, the primary symptoms of SIBO, that’s the first thing to address. If you have recurrent SIBO, finding and addressing the root cause is important, and if it’s autoimmune in nature, using prokinetic supplements, and no matter what the root cause, spacing out your meals and periodically using antimicrobials and some type of SIBO diet like low FODMAPs or the Biphasic diet, is usually necessary. I did an entire episode on recurrent SIBO, episode 83, from October of 2022, so check that out for more information.

Then there are basic lifestyle interventions that can help if you suspect this is going on for you and you don’t have obvious SIBO symptoms. Reducing saturated fats, eating a Mediterranean diet rich in fruits, veggies, nuts and legumes, reducing Omega 6 fatty acids found in oils like soybean, corn, cottonseed, sunflower and peanut oils and processed foods that are high in them. Then increasing cod liver and fish oils will help. And unless you eat fatty fishes very regularly, you may want to think about incorporating a regular fish oil supplement in your regime. But look closely to make sure you’re getting plenty of EPA and DHA in your fish oil, because sometimes it’s 1000 mg of fish oil with only 300 mg of EPA and DHA, whereas the highest quality fish oil supplements, like the ProOmega 2000 you can find in my Fullscript Dispensary* has 1000 of EPA and DHA in one capsule. Then eating lots of probiotic foods or taking probiotics can be helpful. And incorporating prebiotic rich foods in your diet or supplementing with prebiotics like inulin and FOS (which is fructooligosaccrides, which won’t be great if you have recurrent SIBO). Inulin and FOS are found in chicory root, Jerusalem artichoke, onions, garlic, asparagus, jicama and bananas, among other things. Those two prebiotics help feed beneficial lactobacilli and bifidobacteria, which can crowd out the pathogenic bacteria.

Then avoiding sugar, excessive salt and surfactants found in processed foods, like polysorbate 80, mono and diglycerides, soy lecithin and carrageenan is also helpful. And then if you suspect your gut immune system isn’t working well, like you keep getting bouts of different gut pathogens, or you know based on your GI Map or other stool test results that your secretory IgA is low, you can use colostrum, or it’s more purified derivative without any dairy, serum bovine immunoglobulin powder (examples of this are MegaIgG 2000 by Microbiome Labs and Immuno gG SBI powder by Biotics Research, and IgGI Shield by Designs for Health, all available in my Fullscript Dispensary*) to protect yourself against pathogenic bacteria. And then nutrients to support secretory IgA production include omega 3 fatty acids, glutathione, glycine, glutamine, phosphatidylcholine, vitamin C and zinc. And then it’s also known that S boulardii probiotics bring up secretory IgA.

You can also support your mucin production, because the mucin layer is what protects the gut barrier, with amino acids like l-threonine, l-proline, l-cysteine and l-serine. Those are all found in Microbiome Labs Mega Mucosa, which is designed to support that mucin layer.

And then the most studied tool for helping with endoxemia are the spore-based probiotics. Microbiome Labs did a 30-day study with their spore-based probiotic, Megasporebiotic, which was published in the World Journal of Gastrointestinal Pathophysiology that showed that it reduced post-prandial (meaning after a meal) dietary endotoxemia by 42% and triglycerides by 24% (where as in the placebo group, there was a 36% rise in endotoxin and 5% decrease in triglycerides).

So I hope that was a helpful introduction to one of the likely drivers of chronic disease that has origins in your gut microbiome. And if you’re struggling with some type of chronic disease, chronic inflammation,  bloating, constipation, diarrhea, soft stool, acid reflux, etc. and want to get to the bottom of it, that’s what I help my clients with. You’re welcome to set up a free, 30-minute breakthrough session with me (Lindsey). We’ll talk about what you’ve been going through and I’ll tell you about my 3- and 5- appointment health coaching programs in which I recommend lab tests, educate you on what the results mean and the protocols used by doctors to fix the problems revealed. Or if you’re ready to jump in right away or can just afford one appointment at a time, you can set up an 1-hour consultation with me.

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