When you eat, the food does not simply nourish and fuel you and all the activities of your busy life; you also feed the billions of beneficial bacteria living in your gut. The makeup of your gut microbiota has the potential to change rapidly, depending on your diet. According to one study, it only takes three to four days for changes to occur, although this occurred much faster with animal-based rather than plant-based diets.
When there is imbalance in the microbiome with more pathogenic than commensal bacteria, which is known as dysbiosis, health issues arise, often stemming from inflammation associated with metabolic endotoxemia. There are ways to manage this with your diet -- but the wrong diet leads to it arising. Knowing more about what contributes to and mitigates metabolic endotoxemia has the potential to prevent and treat many of the common chronic illnesses plaguing Western society today.
What Is Metabolic Endotoxemia?
Metabolic endotoxemia begins with the gram-negative bacteria residing in the gut. These bacteria have lipopolysaccharides (LPS), also known as endotoxin, in their cell wall. When LPS enter the bloodstream, which could be due to intestinal permeability and/or an excess of LPS, it contributes to low-grade inflammation as the body's natural immune systems work to rid the body of the harmful endotoxins. This inflammation is associated with many chronic illnesses including Alzheimer's disease, diabetes, obesity, cardiovascular disease, chronic fatigue syndrome, cancer, inflammatory bowel disease, nonalcoholic fatty liver disease, metabolic disease, infertility, autism, depression, and schizophrenia.
The diet plays a key role in whether you have high levels of circling endotoxins. Your microbiome always has a certain level of gram-negative bacteria and pathogenic varieties. However, the commensal bacteria typically outnumber them, keeping them from triggering an immune response or otherwise causing an issue. However, when there is a shift toward pathogenic species, then more LPS circulates, causing inflammation. The makeup of the bacteria directly relates to the diet.
Certain bacteria prefer to consume protein, sugar, or fat, while others like carbohydrates in the form of fiber. As such, if you consume a high-fat diet, you end up with more bacteria that like fat, while if you consume a lot of fiber, you end up with bacteria that thrive on it. The bacteria that prefer fat and sugar, typical of the western diet, produce more toxic metabolites. This could be one reason why the typical American diet contributes to obesity, metabolic syndrome, and other chronic illnesses. Alternatively, high-fiber diets feed the commensal bacteria, which produce the beneficial metabolites and other protective properties. There are some specific instances in which the diet contributes directly to the development of metabolic endotoxemia.
High-Fat Diets and Endotoxemia
The fuel source most commonly correlated with an increase in the bacteria that produce endotoxins is fat. According to one study, consuming a high-fat diet for four weeks led to a two to three times higher level of plasma LPS concentrations, thanks to an increase in the proportion of LPS-containing bacteria. In this animal study, mice consumed a control diet or a high-fat, carbohydrate-free diet consisting of 72 percent fat from corn oil and lard, 29 percent from protein, and less than 1 percent from carbohydrates for a period of four weeks. The high-fat group had higher levels of LPS compared to the control group. Then, the researchers created a situation mimicking chronic metabolic endotoxemia through continually infusing LPS subcutaneously for one month. The group consuming the same 72 percent high-fat diet had a 2.7-fold increase in endotoxemia, compared to just a 1.4 fold increase in those consuming a 40 percent high-fat diet, demonstrating a dose-related response. The increased levels of LPS correlated with increased body weight and insulin resistance.
Another study supports these findings, demonstrating that mice treated with antibiotics consuming the same high-fat diet as other mice had smaller sized adipocyte, or fat cells, than those who were not treated. For this study, the high-fat diet also constituted of 72 percent fat from corn oil and lard, 28 percent protein, and less than 1 percent of carbohydrates and lasted for a period of four weeks. Treating the mice with antibiotics also improved glucose tolerance compared to the non-treated group.
It is not just in mice that this occurs; one crossover study placed eight healthy human subjects on a typical Western diet for a period of one month and then after a one-month washout period, the same subjects consumed a prudent style diet, which had more fiber and less fat. For this study, both diets had similar caloric intake (2209 for the Western-style diet and 2214 for the prudent-style diet). The Western-style diet was made up of 40 percent of calories from fat, 40 percent from carbohydrates, and 20 percent from protein. It contained 12.5 grams of fiber and 20.8 percent of total calories from saturated fat. The prudent-style diet had 20 percent of calories for fat, with only 5.8 percent from saturated fat. It contained the same amount of protein and 60 percent of calories from carbohydrates, with 31 grams of fiber. Consuming the Western style diet led to a 71 percent increase in the levels of endotoxins in the blood. Conversely, consuming a prudent-style diet correlated with a reduction in endotoxins of 38 percent.
These changes can occur quickly. One study found that within just one day of switching from a low-fat, plant-based diet to a high-fat, high-sugar diet reflecting the Western diet led to changes in the microbiome in humanized mice (germ-free mice colonized with adult human fecal microbiota).
The type of fat consumed plays a key role in the effects on the microbiome. One study found that increasing the omega-6 to omega-3 fatty acid ratio led to more LPS-producing and other pro-inflammatory bacteria in the gut, leading to chronic inflammation. Conversely, low ratios of omega-6 to omega-3 fatty acids increased the number of LPS suppressing and anti-inflammatory bacteria, mitigating the effects of fat on the makeup of the microbiome and leading to little to no systemic inflammation. Ideally, you want your ratio of omega-6 to omega-3 to be as close to 1:1 as possible, while most western diets have a ratio closer to 25:1. This study also demonstrated that the impact on the gut microbiota was due to the fatty acid composition of the gut tissue rather than the direct metabolism of the fats by the bacteria in the gut.
Although many of these studies point to a problem with fat, it does not mean you have to completely avoid fat for your gut health. Instead, choose healthy fats like omega-3 fatty acids.
When discussing high-fat diets, it is important to discuss the popular ketogenic diet, which has been shown to be beneficial in several chronic illnesses. There are limited studies reviewing the ketogenic diet's influence on the microbiome, especially compared to other diets. One study found that the ketogenic diet reduced inflammation in mice with acute endotoxemia. Other studies have found the ketogenic diet to alter the microbiome. A study on humans consuming the ketogenic diet for three months found a statistically significant increase in Desulfovibrio species, which is a sulfur-producing bacteria that might contribute to dysbiosis. Evidence is limited at this point as to the effects of the ketogenic diet on the microbiome and metabolic endotoxemia, particularly in the long-term.
Nutrient Deficiencies and Endotoxemia
It is not just about feeding the bacteria the right food; dysbiosis and metabolic endotoxemia can also arise through poor gut health. Issues such as intestinal permeability play a role in leading to systemic inflammation. When you are deficient in certain nutrients, it can set the stage for these gut problems, causing a domino effect that ultimately ends with one of the chronic issues listed above.
According to a review study, the major nutrients that affect the gut and microbiome, and for which a deficiency might contribute to metabolic endotoxemia, are vitamin D, zinc, magnesium, vitamin A, vitamin C, and polyphenols. This review points to vitamin D, zinc, and vitamin A deficiencies' roles in impacting the epithelial cells of the gut, which is how a deficiency contributes to increased intestinal permeability.
Polyphenols, which are known for their beneficial antioxidant, anti-inflammatory, and cancer-fighting properties, as well as their ability to protect against diabetes and neurodegenerative diseases, also can mitigate metabolic endotoxemia. There are four main classes: stilbenes, phenolic acids, lignans, and flavonoids. Although there are many different structures, no food has just one type; instead, these different classes act together in a synergistic manner to provide the health benefits. Some foods rich in polyphenols include green and black tea, coffee, red grapes, chokeberries, bilberries, dark chocolate, flax seed, plums, blueberries, black beans, and olives. You might be familiar with some of the different categories of polyphenols, including curcumin, quercetin, resveratrol, proanthocyanidins, apigenin, chlorogenic acid, hesperidin, rutin, and ellagic acid, especially as many of these have been extensively studied for their health benefits.
The small intestine absorbs only a small amount, less than 10 percent, of polyphenols, leaving around 90 percent for the microbiota to metabolize. This means that the microbiota is essential for providing many of the health benefits of polyphenols. Additionally, intake has the potential to alter the gut microbiome makeup through inhibiting the growth of certain pathogenic bacteria while not affecting the growth of the commensal species.
What You Can Do
So, how can you mitigate the risk of developing metabolic endotoxemia? First and foremost, through concentrating on feeding the good bacteria and not the bad while also ensuring that you create a healthy environment in your gut for your friendly bacteria to make a nice home.
There are four main categories of action for preventing and/or treating metabolic endotoxemia:
- Reducing and limiting the amount of endotoxins created through reducing the number of gram-negative bacteria in the gut
- Preventing and repairing any intestinal permeability or leaky gut
- Detoxifying and clearing the endotoxins
- Treating the inflammation caused by endotoxins
There are many different dietary approaches to supporting one or more of these components:
Overall diet: The first place to look for preventing or reversing metabolic endotoxemia is your overall diet. Based on the studies above, you want to avoid consuming lots of highly processed carbohydrates, sugar, alcohol, and unhealthy fat.
Instead, you want to choose a high-fiber diet rich in vegetables, fruit, and whole grains. One study found that substituting whole grains for processed grains led to more bacteria belonging to the genus Lachnospira, which is known to produce the beneficial SCFAs, and a decrease in the Enterobacteriaceae, which are known to be pro-inflammatory. Another study also demonstrated that consuming whole grains led to alterations in the gut microbiome and a related reduction in inflammation.
Additionally, you want to opt for healthy fats and aim for an omega-6 to omega-3 fatty acid ratio as low as possible, ideally 4:1 or lower. Care should be taken when choosing to consume a ketogenic diet, as there is insufficient evidence at this juncture to determine the impact of this high-fat diet on the microbiome and metabolic endotoxemia. Work with a health practitioner to see whether this dietary approach is for you and whether or not it needs to be tailored. Some people are doing not a strict ketogenic diet, but a modified one, which takes into account more vegetables.
These dietary changes can have wide-reaching effects. One study incorporated a gut bacteria restoration program known as the Gut Makeover to restore health. This diet incorporated cutting out highly processed carbohydrates, grains, sugar, alcohol, caffeine, and artificial sweeteners and promoting the consumption of fermented foods and vegetables. Although it was a small study with just 20 participants, there was a significant reduction in symptoms for all participants. The reduction in symptoms went beyond just any gastrointestinal symptoms; it included significant increases in emotional wellbeing and cognitive function.
Prevent and Treat Vitamin/Mineral Deficiencies: As discussed above, certain nutrients have the capacity to negatively impact gut health and the makeup of the microbiome. Therefore, it is beneficial to prevent deficiencies, primarily through consuming a nutrient-rich, plant-based diet. Taking supplements as needed also helps to mitigate a deficiency, especially when there are absorption issues.
Prebiotics: Sometimes, the fiber you consume is not enough to reduce metabolic endotoxemia. That is where prebiotics come into play. These are non-digestible fibers that fuel the commensal bacteria in your gut and as such have the capacity to alter the makeup of your microbiome to increase the levels of commensal bacteria. In one study, participants who had type-2 diabetes either consumed 10 grams of inulin, a common prebiotic, or 10 grams of maltodextrin as a control. Those who consumed inulin experienced a significantly decreased in their fasting blood sugar levels, as well as inflammatory markers, LPS markers in the blood, and HbA1C levels. Other prebiotics, including galactooligosaccharides, have shown similar promise in reducing inflammation.
When consuming prebiotics, always start slowly and build up to the recommended dosage. This reduces the uncomfortable side effects, which might include excess gas and bloating.
Probiotics: Altering the gut makeup through taking probiotics is another way to reduce metabolic endotoxemia. Bifidobacteria have been shown to reduce systemic inflammation and improve metabolic function in mice consuming a high-fat diet. This occurs partially through altering the makeup of bacteria in the gut, lowering the levels of LPS-producing bacteria and other pro-inflammatory bacteria. Consuming bifidobacteria along with a high-fat diet has also reduced the levels of endotoxemia and improved the makeup of the gut bacteria in mice.
Fermented Foods: Traditionally fermented foods, such as sauerkraut, kefir, kimchi, and yogurt have numerous health benefits. Many of these might be connected to the beneficial microbes in fermented foods. Furthermore, these foods have nutrients that promote gut health, such as polyphenols and prebiotics, enhancing the health benefits.
When choosing fermented foods, it is important that you select varieties that incorporate the traditional fermenting process. Many foods commercially marketed go through a different process, which does not have the same beneficial components as fermentation.
Polyphenols: As discussed, the polyphenols in plant foods might provide protection against metabolic endotoxemia. Polyphenols are found in plants, including vegetables, nuts, herbs, tea, cocoa, and fruits. One study reviewed the benefits of cranberry extract, which is very rich in polyphenols, on the gut microbiota. The researchers found that in the mice that consumed a high-fat diet, high sucrose diet with the addition of cranberry extract had less visceral obesity and gained less weight than those that consumed the same diet without the cranberry extract. Additionally, the mice had lower markers of inflammation, oxidative stress, insulin resistance, and cardiovascular disease. One way in which cranberry produced these benefits was through increasing the number of Akkermansia bacteria, which degrade mucin and are linked to protection against metabolic syndrome.
It is super easy to take advantage of the polyphenols in food: eat a wide spectrum of colorful, plant-based foods. Some of the foods and beverages richest in polyphenols per serving include green tea, red wine, flax seed, olive oil, berries (including strawberries, blueberries, raspberries, blackberries, and elderberries), plums, apples, artichoke heads, coffee, hazelnuts, pomegranate juice, spinach, and black beans.
Cocoa: Although fat and sugar, ingredients often included in chocolate treats, might contribute to dysbiosis and metabolic endotoxemia, you do not have to completely forgo your chocolate addiction. One study found that cocoa reduced the level of endotoxins in the blood by 40 percent, thanks to its rich polyphenol content. In this study, mice were fed a high-fat diet, a low-fat diet, or a high-fat diet with 8 percent unsweetened cocoa powder. In those who consumed the cocoa powder, there was not only a reduction in endotoxins; there was also an improvement in the gut barrier function and a reduction in inflammatory markers, among other improvements.
The way to benefit from the many benefits of cocoa and its rich flavonoids is to choose pure cocoa or dark chocolate with at least 70 percent cocoa and minimal sugar and other added ingredients. Also, limit your consumption to a few squares per day as part of a generally healthy diet.
There are other actions you can take to fight against metabolic endotoxin. For starters, healing any gut inflammation or intestinal permeability with products such as berberine, glutamine, whey protein, and/or curcumin can go a long way towards mitigating some of the issues that coincide with endotoxemia. Some of these might also have a direct effect on the makeup of the microbiome and mitigate the amount of LPS in the bloodstream, reducing the inflammation that contributes to chronic disease.
Conclusion
These nutrients, herbs, and food sources have the capacity to provide numerous benefits to your gut health, mitigating metabolic endotoxemia and thereby helping with diseases to which the systemic inflammation either triggered or exacerbated. However, that does not mean you need to go out and buy all of the products in one fell swoop.
The best action is to start in the simplest place: change your diet to a predominantly plant-based diet with lots of fiber and colorful food. Add some probiotics if you feel you suffer from dysbiosis. If you know you are deficient in certain vitamins or minerals, then supplementing might help as well. Once you have started to provide the right substrates to fuel your bacteria and keep your gut healthy, then you can determine whether or not something else is missing, or if an anti-inflammatory herb might help, and incorporate it to continue to reduce the effects of endotoxemia.
Be sure to make the changes, especially those beyond just to your diet, under the supervision and counsel of your doctor or another medical professional, especially if you are on medication for any serious illness, such as diabetes, cardiovascular diseases, an autoimmune condition, or cancer.