Do Gut Bacteria Influence Autoimmunity?

Autoimmune disorders are conditions that occur when the body’s immune system attacks its own healthy tissues. There are many different autoimmune conditions, depending on which healthy tissues are attacked. Some examples include multiple sclerosis, rheumatoid arthritis and lupus.

Autoimmune conditions are often thought of as “rare” (1) because most of the individual disorders affect a relatively small number of people (2). As a disease class, though, autoimmune disorders are actually among the most common conditions in the United States.

In 2012, the U.S. National Institutes of Health reported that a staggering 23.5 million Americans have at least one autoimmune disease. According to the American Autoimmune Related Diseases Association (AARDA), however, even this remarkable number may be significantly too low, since it was calculated using data concerning diseases that are entirely autoimmune mediated. The AARDA estimates that, if all diseases believed to have any autoimmune component were included in the calculation, the real number of Americans affected by autoimmunity may actually be closer to 50 million.

That means that up to 20% of the population — or 1 in every 5 people — may suffer from autoimmune symptoms.

And autoimmune symptoms can be extremely severe. Depending on the tissues being attacked, autoimmune diseases can cause intense pain, disability, loss of quality of life, loss of income, and even promote premature death. (1, 3)  

Genetics are believed to play an important role (4), but so are a wide variety of environmental factors, such as birth-weight, infections, (5) dietary intake of certain compounds (like gluten, mercury or tryptophan), and exposure to toxins from things like cigarette smoke, air pollution and paint thinners.

While all of these factors have interesting implications for the development, prevention, and treatment of autoimmunity, this article will focus on the newly discovered connections between autoimmunity and the health of your gut microbiota.

Not only are these connections now among the most solidly established, (6, 7) they may also ultimately provide some of the most practical opportunities to develop new treatment options, since, unlike many other factors, gut bacteria are relatively easy to manipulate. (8, 9)

To fully understand the links between autoimmunity and gut bacteria, though, let’s first take a quick step back and look at how your immune system normally works, and what researchers now know goes wrong in autoimmune diseases.

THE HEALTHY IMMUNE SYSTEM & SELF-TOLERANCE

If you think about it, your immune system has a really tricky job. It has to scan your whole body all day, everyday and find dangerous bacteria, infectious viruses, and sick or malfunctioning cells and kill them. If it misses any, you may end up with a serious infection or cancer, either of which could kill you — so it really can’t let any slip by!

On the other hand, your immune system also can’t overshoot and kill cells if it’s not positive they are dangerous because if it kills off your healthy cells, your organs can’t work. Of course, that can be fatal as well!

The immune system has to find the perfect balance: find each and every danger while leaving each and every healthy cell alone.

In order to be able to do this, the human body has evolved a very sophisticated network of immune cells that regulate each other directly (via proteins bound to their surfaces) and indirectly (via special hormones called cytokines).

There are hundreds of types of cells involved in keeping the whole immune system working properly, but for the functions that prevent/cause autoimmunity, the relationships between individual members of a family of cells called T-cells are considered among the most important. (6, 7)

There are three key members of the T-cell family: cytotoxic T-cells, helper T-cells, and regulatory T-cells.

  1. Cytotoxic T-cells (Tcyt-cells) are the cells responsible for actually killing a sick or malfunctioning cell once the rest of the immune system has found it.
  2. Helper T-cells (Th-cells), like their name suggests, help the cytotoxic T-cells. They double check that the cell really needs to be killed and gives the Tcyt-cells the “green light” to actually go through with it. They do this both via protein signals on their surfaces and the release of a special mixture of cytokines. Without these signals from Th-cells, Tcyt-cells are pretty powerless.
  3. Regulatory T-cells (Treg-cells) act as a counter-balance to cytotoxic and helper T-cells. Treg-cells use the proteins on their surfaces and a different mixture of cytokines to call off Tcyt-cells and Th-cells from carrying out attacks.

For a long time, researchers thought that under normal circumstances, all Tcyt-cells that recognized healthy cells in your body as dangerous were forced to undergo “apoptosis” (cellular suicide). In healthy people, this system worked perfectly and no self-reactive cells survived. In people who developed autoimmune diseases, however, one (or more) self-reactive Tcyt-cell did not die for some reason, allowing them free-reign to attack their bodies. (2, 10, 11)

Newer research indicates, however, that even in perfectly healthy people, there are always small numbers self-reactive Tcyt-cells that do not undergo apoptosis. They are always present in your body, trying to attack random, healthy organs, but are simply stopped from doing so by constant suppressive signals from healthy Treg-cells. (2, 10, 11) With a normal, healthy balance between Treg-cells and Tcyt-cell/Th-cells, no Tcyt-cells attack any of your healthy cells. This is referred to as the state of self-tolerance.

As you can imagine, though, this set-up to maintain self-tolerance means that even relatively small manipulations in the number of Tcyt-cells/Th-cells or Treg-cells can easily lead to a problem.

If your levels of self-attacking Tcyt-cells/Th-cells increase, or your levels of Treg-cells decrease, you may end up with too many Tcyt-cells/Th-cells and not enough Treg-cells to stop all of them. (6)

If this happens and Tcyt-cells/Th-cells begin killing your healthy tissue, you have, by definition, developed an autoimmune disorder.

SELF-TOLERANCE, AUTOIMMUNITY & GUT BACTERIA

So what do your gut bacteria have to do with any of this?

It turns out, a lot.

In fact, if we wanted to go down to the individual protein and cytokine signals, we would probably have thousands of effects and interactions to talk about!

Luckily, all of the effects gut bacteria have on regulating self-tolerance and autoimmunity can more or less be grouped together into two basic effects which we can talk about more generally:

  1. Regulating the ratios of Th-cells-to-Treg-cells in your body
  2. Influencing your risk of developing more self-attacking Tcyt-cells than normal

Let’s look at these one at a time.

REGULATING HELPER T-CELL TO REGULATORY T-CELL RATIOS

Mounting evidence now clearly shows that the types, numbers, and ratios of bacteria in your gut directly influence how many Th– and Treg-cells you have in your body. (6, 7)

Healthy gut bacteria boost Treg-cell levels in your body by helping your immune system decide to turn immature T-cells into Treg-cells. (6, 7, 12)  Studies in mice have shown that healthy gut bacteria increase Treg-cell numbers through their production of a group of molecules called short-chained fatty acids (SCFAs). (13, 14) Healthy gut bacteria make SCFAs when they break down fiber for energy. (6, 15)

SCFAs can be absorbed into the bloodstream and enter immature T-cells which haven’t decided if they are going to be Tcyt-cells, Th-cells or Treg-cells. There, SCFA turn on the genes that turn them into Treg-cells. (13, 16) This leads to a greater number of Treg-cells in the body, decreasing the chances of a cytotoxic T-cell being able to slip past and start attacking your healthy cells.

Unhealthy gut bacteria, on the other hand, can boost the levels of Th-cells in the body, making it easier for Tcyt-cells to attack your body.

For example, studies show that the growth of even one species of unhealthy bacteria (B. adolescentis) in the gut is able to increase the numbers of Th-cells in the blood. (17)

This effect can even occur just from the wrong ratios of normally healthy gut bacteria in the gut! Overgrowth of the normally healthy E. coli species E. coli 2A, for example, has been shown to to boost Th-cell levels. (18)  

Combined, the effects of decreased healthy bacteria, abnormal ratios of healthy bacteria or the growth of unhealthy bacteria in the gut may shift the ratio of Th-cells-to-Treg cells decidedly in the favor of Th-cells. This can make it much more likely that the “attack” signals outweigh the “don’t attack” signals given to your Tcyt-cells, which can ultimately result in the development of an autoimmune disease. (6, 18)

INFLUENCING YOUR RISK OF DEVELOPING SELF-REACTIVE Tcyt-Cells

In addition to helping to determine which balance of signals your Tcyt-cells receive, your gut bacteria also influence your risk of producing Tcyt-cells that recognize your body as dangerous in the first place.They do this through their role in helping your intestinal wall maintain normal “barrier function.”

Normally, healthy gut bacteria help create a solid barrier between you and the outside world, letting only small nutrients through, while keeping larger molecules and bacteria out. If your gut bacteria become unhealthy, however, you can develop a condition called a “leaky gut” that allows larger molecules to get into your body. (19)

Though rare, some of the molecules that can leak into your gut may be what researchers call “molecular mimics”. (20)

A “molecular mimic” is a molecule that happens to have a structure very similar to one that naturally exists in your body.

If one of these mimics gets into your body, your immune system correctly recognizes it as foreign and mounts a defense. As part of this defense, new Tcyt-cells are made that specifically recognize the molecular mimic. Unfortunately, these Tcyt-cells may also accidentally also recognize the mimicked molecule in your body, too. (20) For example, certain human retroviruses contain a protein, VP7, that happens to look very similar to a protein found on human pancreatic β-cells called IA-2. If you become infected with VP7, your body may make Tcyt-cells that correctly identify VP7 as dangerous. Unfortunately, they may also recognize IA-2, since it is so similar. If this happens, these Tcyt-cells may begin attacking the β-cells in your pancreas, leading to type 1 diabetes. (21)

By regulating how many foreign molecules get into your body through your intestinal wall (19), your gut bacteria help determine the risk of your immune system coming into contact with a molecular mimic and producing a Tcyt-cell that will attack both the mimic and your own molecule.

The fewer foreign molecules leak into your body, the smaller the chance one that makes it in will happen to look like one of your own proteins. The more molecules that leak in, the higher the risk!

When combined with the fact that the same unhealthy gut bacteria that cause a leaky gut also promote a high Th-cell-to-Treg cell ratio that encourages Tcyt-cells to kill their targets, you can see how poor gut health can put you at serious risk for autoimmunity.

IMPROVING SELF-TOLERANCE BY HEALING YOUR GUT BACTERIA

Since poor gut health puts you at greater risk for developing an autoimmune disease, it stands to reason that protecting your gut health is likely a good way to help prevent an autoimmune disease from developing.

Here are some diet and lifestyle changes that have been shown to improve gut bacteria balance:

  • Avoid refined sugars and fats – Both processed sugar and fat can induce dysbiosis and a leaky gut, letting more potentially mimicking molecules into your body. Note that the type of fat seems to be of importance; I discuss this in more detail in this podcast episode.  (22, 23)
  • Eat lots of fiber and prebiotics – Fiber feeds your healthy gut bacteria. It can help prevent or reverse dysbiosis. (24)
  • Eat an abundance of phytonutrient and polyphenol-rich fruits and vegetables – Polyphenols can boost levels of healthy gut bacteria.
  • Drink plenty of water – Staying properly hydrated prevents constipation and constipation can promote the growth of unhealthy bacteria. (25)
  • Exercising regularly – Exercise has been shown to boost levels of healthy gut bacteria in your intestines. (26)

Can improving your gut bacteria balance actually treat autoimmune disorders? Is there any evidence that improving gut health may also be helpful for individuals after they have already developed an autoimmune disorder?

Relatively few studies have specifically looked at treating gut health to improve the symptoms of autoimmune diseases.

However, a few possibly useful dietary and lifestyle changes have already been identified. These include:

  • Eat plenty of fiber-rich foods – Fiber feeds the good gut bacteria that make SCFAs and promote Treg-cell development. (12, 28)
  • Add specific probiotics – Some studies suggest that probiotics containing specific bacteria (B. infantilis, for example), may be able to boost Treg-cell levels (29); ultimately, which supplements might be effective for you would be best determined by examining your gut bacteria and identifying which bacteria are out of balance. (6)
  • Consume vitamin A rich foods or take a vitamin A supplement – There is growing evidence that retinoic acid, a metabolite made from vitamin A in the body, works in conjunction with gut bacteria to help them increase the number of  Treg-cells in your body. (30) I would recommend 5,000 IU per day, and potentially more under the supervision of your doctor or dietitian.

As always, it’s important to consult with your medical provider for any treatments for your autoimmune disease.

If you’d like to learn more about how your diet and lifestyle influence your gut health, I recommend checking out my 8-week online course Build Your Biome.

Are you hopeful that scientists will eventually find a way to cure autoimmune diseases by manipulating gut bacteria? Let me know your thoughts in the comments below!

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