Oral Tolerance Part II: The overlooked power of short-chain fatty acids (SCFAs) for immune health, brain health, and food sensitivities

Go here to read Part I: New food sensitivity issues on AIP? The oral tolerance protocol

In my first article on oral tolerance, I talked about why many people develop an increasing number of food sensitivities on restrictive healing diets and what to do about it. The primary cause is called loss of oral tolerance, and it essentially means your immune system has lost the ability to appropriately manage the food you eat. As a result, it starts reacting to everything.

In this follow up article, I delve more deeply into some finer details of these concepts, giving you more information on the history and importance of the gut microbiome and the incredibly important role of short-chain fatty acids, or SCFAs.

SCFAs are the most overlooked and under-utilized compounds in functional medicine today, and have profound impacts on your gut, immune, and brain health.

Penicillin’s discovery shoves gut microbiome research into the shadows

In 2005, the National Health Institute (NIH) created the $150 million Human Microbiome Project to better research the microbiome. It has been a boon to our discoveries about human health and how to better treat disease.

Professor Metchnikoff by Wikimedia Commons.

However, as groundbreaking as this science has been, it is actually well behind the curve; the first major study on the human microbiome was conducted more than 100 years ago in the early 1900s. Back then, Russian microbiologist and deputy director of the Pasteur Institute Elie Metchnikoff showed that friendly gut bacteria and fermented foods were vital to good health.

Although he received a Nobel Prize for his work, his microbiome work faded into obscurity and was completely eclipsed 20 years later by the discovery of penicillin. Anyone who has seen antibiotics knock out a dangerous infection knows penicillin was a revolutionary discovery.

However, it also created a “kill everything” mentality in medicine without incorporating Metchnikoff’s vitally important findings about the influence of gut bacteria on health and immunity (Metchnikoff continued to drink sour milk daily and is now known as the “father of natural immunity”).

Now, thanks in part to antibiotic-resistant bacteria, we have come full circle to the gut microbiome and ground-breaking findings, such as the use of fecal transplants. Researchers have found fecal transplants from healthy donors can alter the gut bacteria in an infected person to eradicate antibiotic-resistant infection.

That’s right — they take poop from a healthy person and use it to inoculate the gut of an infected person. It’s working so well the FDA has approved the procedure for certain strains of resistant bacteria. Imagine if we had just continued to follow Metchnikoff’s path in the first place.

Microbiome researchers are also learning what supplement marketers don’t want you to know, that there is no perfect probiotic. Several thousand species of bacteria have been identified so far, and it’s no longer appropriate to designate some as good and some as bad. It’s more complex than that and involves their relationship to one another, the person they inhabit, and the outside environment.

The environment plays such an important role in the microbiome that scientists can tell a lot about a person simply by analyzing their gut bacteria, such as whether they were born by C-section or vaginally or where they live on the planet. In fact, researchers discovered people living in the United States have the least diverse gut bacteria of the populations studied, with microbiome diversity falling well below the second least diverse population.

Although we can alter our gut microbiome to affect our health, researchers theorize about one-third of the microbiome has a genetic link and is set for life. This may help explain why some people do everything right but constantly struggle with chronic health conditions, obesity, allergies, and immune imbalances. The good news is we can still have some influence on our gut microbiome health by making it more diverse.

One of the key discoveries from the gut microbiome project is that lack of gut bacteria diversity is a primary factor in what makes people unhealthy. Poor diversity makes you more prone to chronic disease, while the more diverse your gut bacteria are the healthier you are. It impacts every facet of health.

As such, every field in medicine is researching the gut microbiome to improve health and reverse disease, with major studies being published on topics that have long since been understood in functional medicine, such as the concept of leaky gut and the importance of gut health to immune and brain health.

Take the Oral Tolerance Quiz

The gut microbiome is a dynamic organ that can change within three days

What are some factors that cause poor gut diversity? They include:

Eating meat and dairy from animals raised on antibiotics
Not eating enough produce
Eating the same foods over and over, even if they are healthy foods
Taking antibiotics
Excessive alcohol consumption
Pesticides and herbicides

The key to a healthy gut microbiome is to consume a diversity of produce and other whole plant products in your diet (eating a wide variety of animal products is not going to diversify the microbiome).

Researchers are beginning to refer to the microbiome as a dynamic organ that can change within three days and is more complex than the liver.

Jobs this microbiome “organ” performs include:

The gut microbiome makes nutrients. The gut microbiome makes 50 percent of vitamin K, as well as folate and most B vitamins. An unhealthy microbiome can explain why people take handfuls of supplements yet are still deficient in important vitamins. Our bodies are also very dependent on the fat-soluble forms of vitamin A, E, D, and K, all of which depend on a healthy gut microbiome.
The gut microbiome activates polyphenols, antioxidant plant compounds. These polyphenols depend on a healthy microbiome to be metabolized into a usable form. For instance, soy, ginseng, and green tea extract all contain compounds that are active only when metabolized by the gut microbiome.
The gut microbiome regulates your metabolism and how you use calories and insulin. Researchers are finding obesity is linked to imbalanced gut microbiome profiles that may have started in infancy. Many obese research subjects have poor microbiome diversity while their lean counterparts show more diversity. This means the obese person’s gut will harvest more energy and store fat more easily from the same amount of calories a thin person eats. Microbiome research is going to profoundly impact how we treat diabetes and obesity in the future.
The gut microbiome influences immunity.
The gut microbiome influences brain health. Seniors that lack microbiome diversity are more susceptible to neurodegenerative diseases such as dementia and Alzheimer’s. The gut microbiome is also linked to mood and psychiatric disorders and other brain-based disorders.

Gut bacteria diversity starts before and during birth

It was once believed babies were born with a sterile gut that began to colonize with different bacteria in the vaginal canal during birth and then after from the environment. Now we know bacteria in the amniotic fluid begins to colonize the infant’s gut before it’s even born.

In fact, we can see this in premature infants, who show less gut bacteria diversity than full-term babies, and it’s possible survival rates are linked to this diversity. This also means that a woman’s microbiome will have a lifelong impact on the microbiome of her children.

Whether a child is born vaginally or via C-section also creates lifelong microbiome signatures. A baby born vaginally will be inoculated with bacteria from the vaginal wall while a baby born via C-section gets its bacteria from skin.

This helps explain why babies born via C-section have microbiome signatures that predispose them to obesity. Some research also showed mice that were delivered via C-section and received their gut bacteria from skin contact were more depressed and anxious than mice delivered vaginally.

Additionally, breastfeeding makes a big difference in a baby’s gut microbiome health compared to formula feeding. You can see now why babies born via C-section and fed formula have a higher risk of obesity and other health issues.

These children go on to be more susceptible to childhood illnesses such as chronic ear infections that require antibiotics, which only further reduce microbiome diversity and promotes obesity. In fact, research shows penicillin can induce obesity!

This isn’t to make you feel guilty if your child was delivered via C-section, but rather to give you information to better understand your health or your child and areas where extra support may be needed.

It also will help you be realistic about your health outcomes. If you grew up with a severely compromised gut microbiome, your health journey may be about having more good days than bad days versus health perfection.

Also, it’s important to realize a microbiome issue doesn’t necessarily produce gut symptoms. Instead, symptoms could be chronic pain, fatigue, stubborn autoimmune symptoms, brain fog, mood disorders, memory loss, and more.

The hidden treasure in microbiome diversity: Short-chain fatty acids (SCFAs)

Why is gut bacteria diversity so important? Because diverse and plentiful gut bacteria produce enzymes that in turn raise levels of short-chain fatty acids, powerful gut signaling compounds with far reaching effects on brain and other parts of the body. The three primary SCFAs critical to health are:

Butyrate
Propionate
Acetate

Bacteria not only produce SCFAs, but also need SCFAs to produce more SCFAs in a mutually beneficial cycle.

SCFAs also act as signaling molecules and bind to cell receptors, meaning they are critical for influencing many functions in the body.

In fact, SCFAs are the most under-utilized yet most effective way to deal with many gut, immune, and brain issues. I have been using them significantly more in my practice in the last two years and seeing improved results.

Low-calorie dieting paradigm woefully outdated — gut bacteria and SCFAs are key

SCFAs bind to receptors that control appetite and hunger, burn body fat more efficiently, and turn off insulin resistance.

When microbiome diversity is poor and SCFAs are low, a person is likely to always have a large appetite, be prone to insulin resistance, and store fat better than they burn it. You can see why the “calories in, calories out” model is woefully outdated. If gut bacteria diversity is lost, the signaling properties of SCFAs are lost, and the result is an “obese microbiome.”

Scientists were able to demonstrate this in a study involving lean and obese subjects. Using fecal transplants, they inoculated the guts of obese men who had high blood pressure and high blood sugar with the gut bacteria from lean men. Within three weeks, 50 percent of the obese subjects experienced weight loss and improvement of the symptoms associated with high blood sugar.

The effects from a single treatment only lasted about three months, but it’s a breakthrough finding in the treatment of diabetes and obesity. It also provides additional insight into why the nation with the lowest diversity in the gut microbiome also has the highest rates of obesity.

This type of study was first performed in mice, in which obese mice were made lean and lean mice were made obese simply by inoculating them with each other’s gut bacteria.

A similar mechanism was also demonstrated in a study of healthy pregnant women. In the third trimester, the women were found to develop the microbiome of an obese person in order to harvest more energy for the pregnancy. Many female patients of mine have complained of being unable to lose the pregnancy weight after their second or later births and it’s worth exploring whether getting “stuck” in the pattern of an obese microbiome is a reason why.

With ample plant fiber and diversity of gut bacteria, insulin and appetite come under control and the body is able to burn calories more efficiently versus being more efficient at storing them.

The possibilities of altering the gut microbiome as a treatment for diabetes and obesity has made diabetes researchers very excited these days.

Take the Oral Tolerance Quiz

Gut bacteria diversity and the brain

Another exciting area of research is the effect of gut bacteria on the brain, including on mood and personality. Researchers have been observing fascinating effects of gut bacteria on mice.

For instance, researchers used brain scans to study brain development in normal mice and in germ-free mice with no gut bacteria. All the germ-free mice showed impaired brain development. Why? The gut microbiome acts as a signaling organ that influences cell migration, a necessary part of brain development, and brain derived neurotrophic factor (BDNF), which plays a role in learning and memory. In other words, a healthy and diverse microbiome is essential to brain development and health.

Given what we now know about the gut microbiome and the brain, it’s time to explore this connection in children, even starting in the womb. I look forward to research that may help us one day better treat children with autism, learning disorders, allergies, food and chemical sensitivities, asthma, skin disorders, and so on that have become so common today.

We also have to stop thinking of the brain and the gut as two separate entities because they are intimately connected. Anatomically, you can follow the path of the vagus nerve from the brainstem into the gut. The vagus nerve is the highway through which signals from hormones, neuropeptides, and bacteria travel back and forth between the gut and the brain.

For instance, researchers have discovered that Parkinson’s may have its roots in unhealthy gut bacteria that trigger degeneration in the dopamine centers of the brain, thanks to communication via the vagus nerve.

Just as we saw what happens to obese people and mice who received the gut bacteria from their lean counterparts, so can we see similar effects on mood and personality. A variety of studies have shown that gut bacteria can make timid mice courageous, aggressive mice calm, relaxed mice anxious and paranoid — and vice versa.

Imagine the implications for people struggling with anxiety because of their microbiome signature. This isn’t to say all cases of anxiety or other mood disorders are bacteria-based. After all, in the Dutch obesity study, only 50 percent of the obese, pre-diabetic subjects responded to inoculation with gut bacteria from lean subjects. We still need to learn why some subjects respond to bacterial inoculation and not others.

The three types of biotics

Most people are familiar with probiotics, the healthy bacteria we can take as supplements or have in our guts. Some may also be familiar with prebiotics, the plant fibers gut bacteria need as a fuel source.

A third type of biotic is postbiotics. These are the metabolites, or by products, created by bacteria when they digest prebiotics. Examples of postbiotics are SCFAs, perhaps the most influential postbiotic. Other postbiotics include lipopolysaccharides (LPS) — inflammatory compounds created by infectious bacteria.

Postbiotics significantly influence brain function, both positively and negatively. Bacterial infection and inflammation in the gut causes inflammation in the brain, a leading cause of brain degeneration. In other words, fire in the gut means fire in the brain.

Unfortunately, we can’t feel inflammation in the brain as the brain doesn’t contain pain fibers. Instead, brain inflammation symptoms include brain fog, depression, anxiety, irritability, and memory loss. Although brain inflammation may cause loss of brain function, it won’t cause physical pain. (Headache pain is believed to happen when dilated blood vessels press on surrounding nerve fibers.)

Likewise, gut inflammation does not necessarily cause gut pain because the gut doesn’t have pain fibers. Abdominal pain happens when these nerve fibers on the outside of the gut walls are activated by distension. However, in most people gut inflammation and leaky gut don’t “hurt” in the gut, though they may cause many troubling symptoms or pain elsewhere in the body due to inflammatory compounds traveling from the gut into the bloodstream.

Therefore, it’s important to be aware of symptoms of brain and gut inflammation since you won’t feel them the way you will feel inflammation in a joint.

Inflammation makes its way into the brain not only through the vagus nerve but also through a leaky blood-brain barrier. The proteins that cause leaky gut also cause leaky brain, and if you have leaky gut you can be sure you also have leaky brain. You can measure LPS and protein antibodies that identify leaky gut and leaky blood-brain barrier through Cyrex Labs.

The microbiome and heart disease

When most people think of heart disease risk, they think of red meat and cholesterol. However, studies show your microbiome plays a role in heart disease risk. For instance, red meat promotes arterial plaque in some people but not others depending on their microbiome. For the high-risk groups, carnitine, an amino acid in meats, metabolizes into a compound that damages the vascular system. When researchers treated the at-risk group with antibiotics, they saw a drop in the carnitine metabolite that damaged blood vessels.

The same has been found with salt and high blood pressure. Some people’s microbiome makes them prone to high blood pressure from salt and, so far, researchers haven’t figured out a way to alter that.

This kind of research gives us an idea of what a health checkup might look like in the future and how treatments and advice can be customized by assessing each person’s microbiome signature. It also will hopefully shift health care and popular culture away from shaming people for their health issues or weight.

Improving your gut microbiome health and diversity

Although the science shows about one-third of our microbiome is set for life, the good news is we can still influence the other two-thirds with sometimes profound improvements in health and well being.

In my article on oral tolerance and in my oral tolerance program, I talk about the ways in which you can significantly improve your gut microbiome health. This will impact all facets of your health, including your ability to have fewer food sensitivities and tolerate more foods.

As I mentioned before, I also believe SCFAs are one of the most under-utilized nutritional compounds that can have a profound effect on your immune, brain, and gut health.

However, it’s not enough to simply take SCFA supplements. SCFAs need an environment rich in fiber from a diet that is predominantly plant-based. SCFAs help fuel the production of more SCFAs, so good health requires a symbiotic relationship between gut bacteria, a diet high in plant fiber, and SCFAs — this is an area where you can really influence your health on your own.

Also, while butyrate and the other SCFAs may be vital to a healthy gut microbiome, they do not fight off the bacterial and yeast infections in your gut, nor do they compensate for a diet high in sugars and junk foods that promotes an infectious environment. You will have to do the work toward that end yourself as well.

The importance of SCFAs for repairing leaky gut

SCFAs and butyrate in particular are vital to healthy gut function and repairing leaky gut:

Sufficient butyrate and other SCFAs nourish the mucosal lining of the gut. In fact, poor gut bacteria diversity is a factor in causing leaky gut in itself because your beneficial bacteria may feed on your mucosal lining to survive in the absence of sufficient plant fiber.

Butyrate binds to proteins that promote blood flow to the gut. In addition to oxygen, healthy blood flow to the gut also delivers nutrients and healing compounds and helps remove harmful compounds so the gut can function more efficiently.

Butyrate helps dampen inflammation in the gut. It does this by inhibiting inflammatory immune compounds and binding to regulatory T cells, activating them to dampen inflammation. In fact, SCFAs train T regulatory cells to fight autoimmunity in the brain and block the response that causes multiple sclerosis.

Butyrate inhibits over active dendritic cells that lead to loss of oral tolerance.

Butyrate plays a role in the synthesis of tight junction proteins. Tight junction proteins comprise the gut barrier, allowing in nutrients while keeping out undigested foods, bacteria, yeast, and other pathogens. Leaky gut happens when these tight junction proteins break down. In fact, butyrate is so essential to gut health that a butyrate deficiency is all that’s needed to acquire leaky gut absent of infections or inflammatory triggers. Research has shown the gut mucosa receding like a melting ice cap in the absence of sufficient butyrate.

SCFAs can mitigate the effects of antibiotics.

Supplementing with SCFAs

The best way to boost your supply of SCFAs is to eat an abundant and diverse array of produce. Switch it up regularly, explore the produce aisles, and shop in markets that carry produce you’re not accustomed to in order to surprise your gut with new plant fibers.

That said, you may benefit from supplementing with SCFAs as they will help your existing bacteria turn all that plant fiber into a bounty of SCFAs.

When you start taking a SCFA supplement, start with one capsule and work your way up. You can mix it in with food if you like; that’s an easy way to get it to children. If you are breastfeeding, your baby will get it from your breast milk. Some people even like to add them to an enema bag.

If you feel an energy boost from one capsule, that’s a sign your gut microbiome is in poor shape and your gut bacteria diversity and SCFAs need support.

Work your way up to two capsules twice a day. Some people take more. It usually contains sodium, so make sure to drink plenty of water and not overdo it.

Another key nutrient to support boosting SCFA levels is glutathione. Glutathione is a master antioxidant and can dampen inflammation in the gut — gut inflammation is one of the primary factors inhibiting gut bacteria diversity so it’s important to dampen it.

I tell my patients to take their butyrate supplement with a mix of veggies (including a veggie smoothie you make in the blender — but watch your blood sugar and go easy on the fruit juice) and some high quality, absorbable glutathione, such as s-acetyl glutathione, oral liposomal glutathione, or a combination of the two.

You can also take glutathione precursors such as n-acetyl cysteine.

Take glutathione or glutathione precursors several times a day and experiment with dosages to see what has an effect on dampening inflammation.

Conclusion

I realize the information surrounding the gut microbiome, SCFAs, and oral tolerance is vast, but hopefully it gives you new understanding into what the body desires for optimal gut, immune, and brain function.

What excites me most about this information is how far reaching the potential of these therapies is and the fact that the average person can make big changes on their own at home.

It’s important to remember many other factors can be at play in your health journey and that addressing gut microbiome and SCFAs isn’t meant as the single magic bullet. Chronic undiagnosed infections, inflammatory triggers, dietary issues, lifestyle or emotional stressors, anemia, autoimmunity, and brain function disorders are just a few of the issues that can play a role in your health.

However, I hope this information gives you another puzzle piece to fit into your overall health strategy.