Can the Microbiome Affect Crohn’s Disease and Ulcerative Colitis (IBD)?

ibd ulcerative colitis crohns

Inflammatory Bowel Disease (IBD) refers to a group of diseases characterized by changes in the intestinal immune system and chronic inflammation of the intestinal walls.

The most common of these conditions are Crohn’s disease and ulcerative colitis. (1, 2, 3, 4)

Crohn’s Disease

Crohn’s disease (CD) is an inflammatory bowel disease that can affect any part of the digestive tract, from mouth to anus. (2, 5)  It causes patches of inflammation that extend deep into the intestinal wall, sometimes going all the way through. These inflamed patches are typically separated by areas of healthy tissue.  (2, 5)

The inflamed patches of intestine are very painful and the defining symptom of Crohn’s disease is abdominal pain. Poor digestion and absorption of food by the inflamed gut walls also leads to diarrhea (which can be bloody or mucus-filled), weight loss, and nutritional deficiencies (particularly anemia and vitamin B12 deficiencies). (3, 5)

Though the diagnosis of Crohn’s disease mostly relies on changes in the digestive tract, the overactivation of the immune system in CD is not restricted to the gut. Abnormal immune function in the disease leads to a variety of non-digestive symptoms, as well, including:  (3, 5)

  • fever
  • arthritis (in the joints or spine)
  • canker sores
  • inflammation of the eyes and
  • inflammation of fat cells below the skin (erythema nodosum)

Ulcerative Colitis

Though similar to Crohn’s in many ways, ulcerative colitis (UC) has some distinct features.

In UC, the immune system only attacks the surface of the colon and/or rectum, not deep into the intestinal wall.  The inflammation in UC is also continuous, rather than patchy. It never skips over patches healthy tissue. (2, 5)

These differences in nature of the intestinal inflammation in UC lead to slightly different symptoms.

Rather than abdominal pain, the defining symptom of UC is frequent, urgent and severe diarrhea that is nearly always bloody.

UC can cause abdominal pain and unwanted weight loss, but, since the inflammation in UC is more limited and doesn’t involve small intestine (where nutrients are absorbed), these symptoms are less common in CD. (2, 5)

Though the intestinal inflammation in UC is less widespread than in CD, it would be a mistake to think the immune dysfunction itself is somehow “limited”. It is still significant and has full-body effects. Similar to the body-wide symptoms of Crohn’s, UC can cause: (2, 5)

  • fever
  • osteoporosis
  • mouth ulcers
  • leg ulcers
  • arthritis
  • inflammation of the bile ducts
  • inflammation of the eyes
  • formation of blood clots in the legs or lungs

What causes IBD?

The exact cause of IBD has baffled researchers for decades. (2, 6)

Studies clearly indicate that there are genetic factors at play. Population studies show different rates of IBD amongst different ethnicities and a strong clustering of IBD within families. (3, 4, 7) Detailed genetic studies have even been able to find over 160 unique gene mutations directly linked to an increased risk of IBD. (7)

But data also clearly shows that IBD isn’t an actual genetic disorder, either.

None of the 160 risk genes identified are common to everyone who gets IBD. (7)

There is no decisive inheritance pattern for IBD, like one sees with true genetic disorders such as hemophilia or cystic fibrosis. (8)

IBD can’t even be the result of a combination of high-risk genes since identical twins (who have identical DNA) don’t always both get IBD if one does. (9)

To summarize, genes play a role in IBD development, but don’t seem to cause IBD.

How does that work?

The leading theory at the moment is best explained by the “loaded gun analogy”. (10)

The Loaded Gun Analogy

As the name suggests, the “loaded gun analogy” imagines the development of IBD to be similar to firing a bullet from a gun.

In order to fire a bullet from a gun you need to do two things: First, you have to load a bullet into the chamber. Then, you have to pull the trigger.

If you leave out either of these steps, you can’t actually fire a bullet!

If you load the bullet but don’t pull the trigger, the bullet just sits harmlessly in the gun. And if you pull the trigger, but forgot to load the bullet, nothing happens.

Similarly, researchers now think that developing IBD requires two steps.

The first step (“loading the bullet) comes from your genetic risk. Inheriting IBD-promoting genes acts like loading a bullet into the chamber of the gun.

The second step ( “pulling the trigger”) comes from something completely non-genetic: your environment. The right environment acts like a finger on the trigger of the gun, actually firing the bullet.

If you leave out either of these steps, you don’t actually get IBD. If you have the genes for IBD, but are never exposed to the right environment, your genes sit harmlessly in your cells. If you live in the perfect environment to develop IBD, but have no IBD genes, nothing happens.

Pulling the Trigger of IBD

Clearly, not every environment can “pull the trigger” for IBD, or everyone with a genetic risk would get the disease.

Only specific things in the environment, then, can be capable of “pulling the trigger”.

Have researchers been able to find any solid candidates for these environmental “trigger-pullers”?

Quite a few, actually.

Scientists compared the environments of people who developed IBD and people who didn’t (even though they had a genetic risk) and found lots of differences.

They found that those who got IBD tended to:

  • live in specific parts of the world (North America or Europe) (4)
  • live in cities (11)
  • include less fruits and vegetables in their diet (12, 13)
  • work white-collar jobs (13)
  • be stressed out for long periods of time (13)
  • have been bottle-fed as an infant (14)
  • have been exposed to cigarette smoke (for Crohn’s disease only) (13, 14)
  • have been exposed to excessive air pollution (14)
  • have low vitamin D levels (15)
  • have taken non-steroidal anti-inflammatory drugs (NSAIDs), like ibuprofen (13)
  • not had their appendix removed (ulcerative colitis only) (13)
  • have had an intestinal infection (6, 13)
  • and have an unhealthy balance of gut bacteria (6, 14, 15, 16, 17, 18, 19, 20, 21, 22)

While scientists think all of these environmental factors are important, one has started to stand out over the last few years as one of the most important IBD-trigger: having unhealthy gut bacteria.

Unhealthy Gut Bacteria & IBD

There are 5 known ways that the microbes living in your gut can influence the development of IBD.  

Unhealthy Gut Bacteria Interact with the NOD2 Gene

The NOD2 gene is one of the most commonly mutated genes in IBD. It encodes a protein responsible for recognizing when bacteria are trying to sneak into the body. It sounds the alarm when this happens, telling the immune system to attack.

When it is mutated, NOD2 becomes very sensitive to unhealthy changes in the numbers and types of bacteria in the gut. Even small changes can cause NOD2 to tell the immune system to mount an enormous response.

Unfortunately, an enormous immune response damages the wall of the intestine. This damage is really small — smaller than the tiniest paper-cut you can imagine — but enough that bacteria from inside the gut can end up getting into the wall of the intestine itself.

Once in the intestinal wall, guess what these bacteria do? They are recognized by NOD2 because they are not supposed to be there. Of course, NOD2 tells the immune system to attack more. The wall of the intestine becomes more damaged. More bacteria can get in.

It becomes a vicious cycle that can lead to the symptoms of IBD. (6, 23, 24)

Unhealthy Gut Bacteria Interact with ATG16L1

It sounds kind of crazy, but some white blood cells have to be able to “swallow” bad bacteria before they can kill them. (If you’ve never seen a white blood cell gobble up a bacteria to kill it, you should check it out on YouTube. It looks really cool!)

One of the proteins these immune cells need to be able to “gobble up” bacteria is ATG16L1. If the gene that encodes for this protein is mutated (which it often is in IBD), ATG16L1 can’t do its job. This means that immune cells can’t “eat up” bacteria very well.

If unhealthy gut bacteria trigger immune cells to try to “eat” them, but the immune cell can’t because of a mutated ATG16L1, it has to resort to plan B. Plan B, unfortunately, is really bad for developing IBD.

Immune cells that can’t “eat” bacteria start spewing as many inflammatory chemicals as they can to try to kill the bacteria anyway. These inflammatory chemicals damage the wall of the intestine.

Just as we saw with NOD2, this damage can create a vicious cycle.

More bacteria get into the intestinal wall where it is damaged. These bacteria, who aren’t supposed to be there, activate new immune cells, which try to “eat” them. They can’t, of course, so these immune cells release more inflammatory chemicals. And on it goes. (6, 24, 25)

Unhealthy Gut Bacteria Make Toxins

Some of bacteria that are found in high numbers in the digestive tract of those with IBD can make gut-damaging toxins.

For example, two kinds of bacteria, called D. piger and B. wadsworthia, found at abnormally high levels in IBD, make a chemical called hydrogen sulfide. Hydrogen sulfide is a strong acid that can damage the walls of the intestine. (26, 27)

And, as we saw above, damaging the walls of the intestine can lead to inflammation of the gut wall and IBD.

Unfortunately, it is difficult to tell if you have hydrogen sulfide producing bacteria in your gut, especially your small intestine. Tests for unhealthy bacteria in your large intestine may pick up these toxin-producing bacteria, but a SIBO breath test can’t (yet, at least).  (28)

This makes hydrogen sulfide a potentially potent driver of IBD. Left undetected, this acid can damage gut walls for long periods of time, making it even more likely that the gut inflammation will progress to IBD.

Unhealthy Gut Bacteria Lead to Leaky Gut

Healthy bacteria produce molecules that help the intestinal wall stay strong and healthy. They do this by helping the cells that make up the wall of the intestines produce something called “tight junction proteins.” These proteins seal up the gaps between individual cells to create a seamless wall of cells, with no holes or gaps.

Unhealthy gut bacteria, on the other hand, don’t make enough of the chemicals that help the gut wall make tight-junction proteins. And without enough tight-junction proteins, holes and gaps can start forming in the intestinal wall, leading to a condition called “leaky gut”.

Once your gut is “leaky”, bacteria get through into your body and wreak havoc. They cause the immune system to go nuts, releasing inflammatory chemicals into the intestinal wall and bringing us into the vicious circle of IBD. (29)

Unhealthy Gut Bacteria Cause an Inflammatory Storm

Healthy gut bacteria make a group of chemicals called short-chain fatty acids (SCFAs). SCFAs have an important job in regulating the immune system. They help a group of immune cells, called T-regulatory cells, mature and function.

Mature T-regulatory cells do exactly what their name sounds like they do — they regulate the immune system. Specifically, they help turn off cells that release inflammatory chemicals, such as those damaging the gut wall in IBD.

Unhealthy gut bacteria do not make as many SCFAs, leaving the immune system with fewer T-regulatory cells. This makes it much harder to stop inflammatory chemicals from damaging the intestinal walls and stop IBD from progressing once it starts. (6, 30, 31)

Taking the Bacterial Finger Off the Trigger

Clearly, having unhealthy gut bacteria can be bad news when it comes to developing IBD.

If you have a genetic risk (a close family member who’s already been diagnosed, for example), is there anything you can do to prevent unhealthy gut bacteria from pulling the IBD trigger on you?

Research shows that there are a few things you can to do support healthy gut bacteria and potentially prevent IBD. These include:

  • Quit smoking — cigarette smoke harms your healthy gut bacteria. (13, 14, 32)
  • Limit alcohol intake — excessive amounts of alcohol can harm your healthy gut bacteria. (33)
  • Reduce the use of NSAIDs — NSAIDs can damage the walls of your intestines, making it more difficult for healthy gut bacteria to survive. (13, 34)
  • Eat lots of fruits and vegetables —  fruits and veggies are rich in fiber and prebiotics, both of which help support healthy gut bacteria. (12, 13)
  • Increase your intake of fermented foods or probiotics — These contain healthy gut bacteria which help support the immune system.  (35, 36, 37)
  • Get regular exercise — exercise helps healthy gut bacteria thrive. (38)
  • Drink enough water — proper hydration helps to prevent constipation, which can have negative effects on your gut bacteria can keep your healthy gut bacteria from growing properly. (39, 40)

If you know you are at risk for IBD or have already been diagnosed with IBD, you should absolutely test your gut microbiota.

Testing can identify unhealthy levels of gut bacteria that need to be treated more aggressively with antibiotics or antibiotic herbs.

Un-Firing the Bullet

What if you already have IBD? Can addressing poor gut bacterial health also address your IBD symptoms?

Research shows that fixing imbalanced gut bacteria can help IBD symptoms, but not always. We need more studies to be done in this area, but the current research shows that the beneficial effects of fixing imbalanced bacteria depend on both the type of IBD and the type of treatment used to balance unhealthy bacteria. (6, 41)

But a few treatments seem to be helpful for IBD patients, which I’ll go over below.

Researchers wondered the exact same thing and put it to the test. (6, 41)

Ulcerative Colitis Treatments

Studies show that treatment with the probiotics VSL#3 and E. coli Nissle 1917 are the most helpful bacterial-treatment option.

These probiotics contain purified strains of healthy gut bacteria and have been shown to improve the symptoms of ulcerative colitis better than placebos in multiple studies. (6, 42, 43, 44, 45, 46)

Ulcerative colitis symptoms may also respond to treatment with germinated barley foodstuff, a prebiotic.

Healthy gut bacteria can use germinated barley foodstuff for food and fuel, helping them get the upper hand on unhealthy gut bacteria and regain normal ratios. (6, 47, 48, 49)

Given the response to this particular prebiotic, it would make sense to suspect that other prebiotics, like FOS or GOS, may be useful, as well.

Crohn’s Disease Treatments

Studies show that fecal transplants can be very beneficial for Crohn’s disease patients. (6, 50)

Fecal transplants are medical procedures that do exactly what they sound like. Doctors use stool from a healthy donor without IBD, blend it, filter it and introduce the filtered liquid into the gut. This can be done via an enema, a colonoscopy or a tube threaded through the nose and throat into the gut. (6)

Studies show that fecal transplants are very effective at treating Crohn’s disease symptoms for months at a time. This is mostly true for those who have Crohn’s disease and an intestinal infection with a pesky bacteria called C. difficile. (6, 51)

Treatment Safety

While doctors and scientists believe that prebiotics, probiotics and fecal transplants are generally safe to use, they are not entirely without side effects. (6)

Most side effects are mild and include things like gas, bloating, or diarrhea. Not great when you’re trying to treat digestive issues, but not life-threatening. (6)

In those with IBD, however, there is a slight risk that probiotics and fecal transplants can lead to a very serious side-effect: blood poisoning. (6, 52, 53)

Both probiotics and fecal transplants contain live bacteria that can, in rare cases, get through the damaged gut wall in IBD and into the bloodstream. This is extremely dangerous. It can cause septic shock and death if not treated quickly and properly. (6, 52, 53)

For this reason, it is important that those with IBD discuss all treatments for unhealthy gut bacteria with their doctor and only take over-the-counter supplements under their doctor’s supervision.

Healthy Gut Bacteria: A Magic Bullet?

Even a couple of decades ago, no one imagined that gut bacteria could play such an important role in the development of IBD. Nor would anyone have imagined that the painful, debilitating, sometimes life-threatening symptoms of IBD might be cured with simple, easy treatments to address gut bacterial health.

While that is not yet a reality for everyone — there is no single magic bullet cure for IBD in treating unhealthy gut bacteria — researchers, doctors, and patients are starting to imagine it!

Maybe, with continued research, those dreams just might come true.

Have you been diagnosed with IBD? Have you tried balancing your gut bacteria to help your IBD symptoms? Let me know in the comment section below!

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