Irritable Bowel Disease and the Gut Mircobiome

Irritable Bowel Disease and the Gut Microbiome

Introduction:

    When people ask me what specialty I want to pursue, my wife likes to tease me that my response changes based on whatever unit I’m on in medical school. And there is some truth to that. I’ve tossed around cardiology and orthopedic surgery. Right now, my response might be gastroenterology or endocrinology, which, as you might have guessed, means we are currently doing our GI unit. 

    This week’s topic is irritable bowel disease (I’ll be using the abbreviation IBD from here on out). Why is it important to be informed about IBD? Well, Chron’s disease and ulcerative colitis, the two main forms of IBD are extremely common. Over 3 million Americans have a diagnosis of IBD, meaning that it is likely that you or someone you know currently battles IBD. Additionally, IBD can be developed at any point throughout someone's life. Even though there is a strong genetic component to developing the disease (meaning that you are more likely to develop it if a family member has it), anybody can develop IBD. Many additional factors play into one’s risk for developing IBD including diet, lifestyle, environmental factors, and the gut microbiome. 

    In this post, I will first explain some anatomy to get you oriented with the gut. Then, I will briefly talk about the pathology of Chron’s disease and ulcerative colitis. There is a lot of fascinating, relatively recent research into how the gut microbiome influences the development and progression of IBD, and I will end by diving into emerging research on that topic. 

Anatomy of the Gut:

What I’m about to tell you may ruin eating donuts. So, if you love donuts, proceed at your own risk. When it comes to talking about the gut tube, or the alimentary tract to be fancy, think of it as a donut. There is a tube that goes from your mouth to your anus in an unbroken line, and that is like the hole of the donut. The rest of our body makes up the doughy part of the donut. Basically, we are all walking, talking donuts. Food goes in one side of the tube, gets processed, and comes out the other side. The journey of food through the alimentary tract goes in this order:

• Mouth
• Esophagus
• Stomach 
• Small intestine (which consists of the duodenum, jejunum, and ilium)
• Large intestine (i.e. colon) 
• Rectum
• Anus

Image credit: https://my.clevelandclinic.org/health/body/21758-stomach

Chron’s Disease:

    The first type of IBD (inflammatory bowel disease) is Chron’s disease. As the name “inflammatory bowel disease” implies, it is characterized by chronic inflammation that affects the end of the small intestine and the beginning of the large intestine. While the exact cause of Chron’s disease is unknown, the inflammation is caused by an overactive immune response to intestinal bacteria which causes remodeling of the tissues lining the gut (the layer of tissue lining the inside of the gut tube is called the mucosa) [1]. Patients with Chron’s disease have a characteristic “cobblestoning” appearance with deep fissures in the intestinal mucosa. This can cause a whole host of symptoms ranging from abdominal pain, bloody stool, diarrhea, and constipation to weight loss, joint pain, and fever. Additionally, fat accumulates around the outside of the colon (see image below) as a protective measure to prevent bacteria from passing through the disease-caused fissures and getting into the abdomen.

Image credit: https://www.health.harvard.edu/a_to_z/crohns-disease-a-to-z

    Treatment for Chron's disease generally involves dietary and lifestyle changes, antibiotics, and immunosuppressants to reduce the body’s overactive immune response. In severe cases of Chron’s disease, surgery may be necessary to remove the damaged part of the colon (i.e. large intestine). 

Ulcerative Colitis:

    Ulcerative colitis is similar to Chron’s disease. It causes chronic (meaning long-term) inflammation and ulceration (i.e. formation of sores) in the mucosa (i.e. the inner lining of the intestines) from an overactive response by the body’s immune system. Ulcerative colitis differs from Chron's in that it only affects the large intestine (i.e. the colon). With ulcerative colitis, the colon's mucosal lining becomes compromised, allowing bacteria and toxins to penetrate. This is what causes the immune response. The problem with ulcerative colitis (and IBD in general) is that the immune response is overactive, structurally changing the lining of the gut and causing adverse symptoms.

    Many of the symptoms of ulcerative colitis are similar to those of Chron’s disease, notably cramping in the lower left abdomen, blood in the stool, diarrhea, constipation, fatigue, fever, and joint pain to name a few. Symptoms may come and go with flare-ups and remission. Additionally, like Chron’s disease, the exact cause of ulverative colitis is not well understood. Both genetic and environmental factors play a role in developing the disease. 

Image Credit: https://en.wikipedia.org/wiki/Ulcerative_colitis

Gut Microbiome:

    The mechanisms underlying how ulcerative colitis develops are complex, and we still have a long way to go to fully understand them, but a lot of new emerging research points to connections with the gut microbiome. To explain the gut microbiome simply, lining our intestines - and really throughout our entire gastrointestinal tract from the mouth to the anus - there are tens of trillions of bacteria that have taken up residence within us. They play vital roles such as helping with metabolism, providing certain vitamins, balancing hormones, supporting our immune system, obtaining nutrients from food, and even preventing kidney stones [3]. Our gut microbiome consists of thousands of different strains of bacteria. These bacteria can broadly be placed into three different categories. Bacteria that are beneficial, bacteria that are neither beneficial nor harmful under normal conditions, and bacteria that are pathogenic, meaning they can cause disease.

    When it comes to the development of ulcerative colitis (I did more research on ulcerative colitis and its connections to the gut microbiome, but there exist links between Chron’s disease and the gut microbiome as well), it seems to be caused to a large extent by an imbalance between the beneficial and pathogenic bacteria and the immune response of the mucosal layer (i.e. inner lining of the intestines) [4]. What does imbalance mean? Normally, the body’s immune system prevents bad bacteria from growing while tolerating good bacteria in the gut. Factors like diet and stress have a huge effect on the relative proportions of good and bad bacteria. It is important to note many, if not all, of the strains of bacteria in our gut create compounds and chemicals that have all sorts of effects. The presence of excessive bad bacteria and the toxins they create stimulates an overreactive response from the immune system that leads to disease, such as ulcerative colitis. 

    You may be wondering if ulcerative colitis can be caused exclusively by an imbalance in the microbiome. One study found “animals raised in a sterile environment did not develop IBD” [5]. This means that animals raised in a lab and kept under conditions where a microbiome could not develop did not get IBD, therefore, the microbiome plays a central role in developing IBD. With this in mind, it is important to clarify that the microbiome is just one piece of the puzzle. Other factors like age, smoking, other underlying conditions, genetics, etc. also play into the big picture of disease development. But what is clear is that maintaining a healthy gut microbiome is crucial to both preventing and managing disease. As the genetic components of IBD become better understood, then more targeted approaches using gene therapy, probiotics, and antibiotics to target specific strains of bad, pathogenic bacteria can be developed, leading to better treatments and better patient outcomes. 

Dietary Interventions:

    First, I want to be clear that the treatment for IBD is complex and should be managed by a physician. Some dietary/lifestyle changes considered to improve the gut microbiome may actually worsen the symptoms of someone who has IBD. For those with IBD, there is currently very little data on beneficial dietary interventions beyond avoiding foods that worsen symptoms, so I cannot make any recommendations for those who have developed IBD.

    That being said, many studies have shown that the typical Western diet, rich in fats, simple sugars, and protein, and poor in fruits and vegetables (basically lots of highly processed foods) leads to decreased microbiome diversity and increased prevalence of IBD [6]. Studies have also repeatedly shown that eating a diet high in fruits, vegetables, and dietary fiber reduces the risk of developing IBD [7]. Eating more of a Mediterranean diet is beneficial in increasing the diversity of the microbiome and decreasing the permeability of the lining of the gut [8] (this means there is less inflammation in the gut which presumably helps decrease the likelihood of developing IBD). I have included a helpful diagram below that depicts what a Mediterranean diet consists of. While I personally do not adhere to a Mediterranean diet, there are aspects of it that I strive to incorporate such as eating more fruits, vegetables, whole grains, olive oil, and seafood. 

Image Credit: https://www.mdpi.com/2072-6643/13/1/7

Probiotics:

    Probiotics are living organisms (i.e. bacteria) that have health benefits when given in proper amounts. They can be taken in pill form or by eating foods with live cultures like yogurt, kefir, sauerkraut, kombucha, or pickles. Generally, they are considered to be safe unless you have an autoimmune disorder or serious medical condition. How do probiotics affect the gut microbiome? Good bacteria in the gut help digest complex carbohydrates, produce vitamins, and lower inflammation. Additionally, they reduce the permeability (i.e. ability for other microorganisms to penetrate the mucosal lining). [9]. 

Smoking:

    This should go without saying, but smoking is bad for overall health. Smoking is associated with a higher risk of developing IBD and worsening the symptoms of someone who has IBD [5].

Conclusion:

    The two types of IBD are Chron’s disease and ulcerative colitis. Both are caused, to a large extent, by dysregulation between the gut microbiome and the body's immune response. Both cause chronic inflammation and changes to the physiological structure of the bowels which leads to a host of adverse symptoms.

    While many factors such as genetics, environmental factors, and other conditions play into the development of IBD, the gut microbiome plays a pivotal role in both the development and progression of the disease. This raises the question of whether taking active steps to alter and improve the gut microbiome can lessen the risk of developing IBD or improve the symptoms of someone with IBD. While there is still much research to be done to answer these questions definitively, it appears that certain interventions can lessen the risk of developing IBD. Those who already have IBD will require more nuanced and intensive treatment that should be managed by professionals. 

    Dietary measures include avoiding foods typical of a Western diet in exchange for more fiber-rich foods like fruits, vegetables, beans, nuts, and legumes. Probiotics, including live-culture foods, can also be very beneficial, and smoking should be avoided at all costs. Taking active steps to improve the gut microbiome can lessen the risk of developing IBD and improve overall health. 

Sources:

1. Petagna, L., Antonelli, A., Ganini, C., Bellato, V., Campanelli, M., Divizia, A., Efrati, C., Franceschilli, M., Guida, A. M., Ingallinella, S., Montagnese, F., Sensi, B., Siragusa, L., & Sica, G. S. (2020). Pathophysiology of Crohn's disease inflammation and recurrence. Biology direct, 15(1), 23. https://doi.org/10.1186/s13062-020-00280-5
2. Reddavide, R., Rotolo, O., Caruso, M. G., Stasi, E., Notarnicola, M., Miraglia, C., Nouvenne, A., Meschi, T., De' Angelis, G. L., Di Mario, F., & Leandro, G. (2018). The role of diet in the prevention and treatment of Inflammatory Bowel Diseases. Acta bio-medica : Atenei Parmensis, 89(9-S), 60–75. https://doi.org/10.23750/abm.v89i9-S.7952
3. Zhang, Y. J., Li, S., Gan, R. Y., Zhou, T., Xu, D. P., & Li, H. B. (2015). Impacts of gut bacteria on human health and diseases. International journal of molecular sciences, 16(4), 7493–7519. https://doi.org/10.3390/ijms16047493
4. Shen, Z. H., Zhu, C. X., Quan, Y. S., Yang, Z. Y., Wu, S., Luo, W. W., Tan, B., & Wang, X. Y. (2018). Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World journal of gastroenterology, 24(1), 5–14. https://doi.org/10.3748/wjg.v24.i1.5
5. https://www.acpjournals.org/doi/abs/10.7326/0003-4819-143-12-200512200-00007?journalCode=aim
6. Gerasimidis, K., Godny, L., Sigall-Boneh, R., Svolos, V., Wall, C., & Halmos, E. (2021). Current recommendations on the role of diet in the aetiology and management of IBD. Frontline gastroenterology, 13(2), 160–167. https://doi.org/10.1136/flgastro-2020-101429
7. Ananthakrishnan A. N. (2013). Environmental risk factors for inflammatory bowel disease. Gastroenterology & hepatology, 9(6), 367–374.
8. Merra, G., Noce, A., Marrone, G., Cintoni, M., Tarsitano, M. G., Capacci, A., & De Lorenzo, A. (2020). Influence of Mediterranean Diet on Human Gut Microbiota. Nutrients, 13(1), 7. https://doi.org/10.3390/nu13010007
9. Thomas, C. M., & Versalovic, J. (2010). Probiotics-host communication: Modulation of signaling pathways in the intestine. Gut microbes, 1(3), 148–163. https://doi.org/10.4161/gmic.1.3.11712