New to IBD

Although having certain genes can increase your risk for Inflammatory Bowel Disease (IBD), genetics alone don’t determine whether someone will develop it. Researchers have identified over 200 genetic variants (risk “loci”) associated with IBD, 110 of which are shared with CD and UC ⁶. Many of these are also associated with other immune-mediated diseases like ankylosing spondylitis and psoriasis, which are common extra-intestinal manifestations of IBD.⁷ Many of these genes influence how the immune system responds, how the lining of the gut works, or how your body interacts with the microbes in your intestines.⁸

Still, even with all those genetic markers, researchers estimate that these genetic risk factors explain less than 30% of why IBD occurs in people, which means that environmental and other non-genetic factors must play a large role.⁹

Indeed, over the past several decades, IBD has increased sharply in countries adopting a more “Western” lifestyle, changes in diet, sanitation, antibiotics use, urban living, and other environmental exposures have been strongly linked to that rise.¹⁰ Moreover, recent studies suggest that among people who do develop IBD, environmental factors can strongly influence when the disease appears, sometimes even more than genetics. In one large recent study, environmental exposures explained a significant portion of the variation in age at diagnosis of IBD, while genetic risk was not significantly associated with earlier onset.¹¹

In practical terms: having “IBD genes” may raise your susceptibility, but many people who carry risk genes never develop IBD, because in many cases the “triggering conditions” involve changes in environment, diet, gut microbes, or other life exposures. Because environment appears to be such a big piece of the puzzle, this means there is hope, modifying environmental and lifestyle factors may influence not just risk, but potentially the disease course.

Environmental and lifestyle factors play a crucial role in the risk of developing IBD. Diet, physical activity, smoking, and antibiotic use can influence intestinal inflammation and the composition of the microbiome. 

• Diet: The Western diet, especially a high intake of highly processed foods and a low-fiber diet, can disrupt the intestinal barrier and promote inflammation. 
• Exercise: Physical activity and exercise have been shown to positively influence the diversity of the microbiome. 
• Smoking: has an ambiguous effect: it worsens Crohn's disease, but appears to have a protective effect against ulcerative colitis. Obviously, the benefits of potentially preventing ulcerative colitis do not outweigh the other health risks of smoking. 
• Antibiotic: use can disrupt the gut microbiome and potentially trigger or worsen IBD symptoms.

The gut microbiome is the collection of billions of bacteria, viruses, fungi and other microorganisms that live in the intestines. These microbes play an important role in digestion, the immune system and general health. A healthy balance of the gut microbiome helps digest food, fight harmful invaders and reduce inflammation. It plays a crucial role in maintaining intestinal health. Dysbiosis, or an imbalance in intestinal bacteria, is associated with the development of IBD. 

At the molecular level, several mechanisms contribute to the development of IBD:

• Intestinal Barrier Dysfunction:
  The intestines are lined with epithelial cells, which form a protective barrier between the intestinal contents and the rest of the body. They help with the absorption of nutrients, prevent harmful substances and bacteria from entering the body and play a role in the immune system by sending signals in the event of infections or inflammation. Disruption of this barrier allows the passage of bacteria and antigens, triggering immune responses and inflammation. This is also called intestinal permeability, or leaky gut.
• Cytokine production:
  Cytokines are small proteins released by cells of the immune system to regulate the immune response. They activate other immune cells to help fight infections and promote wound healing. Some cytokines inhibit inflammation and while other cytokines stimulate inflammation, leading to possible tissue damage and increased inflammation. Inhibiting these cytokines is the basis of many current treatments for IBD.  
• Oxidative stress:
  When there is inflammation in the intestines, the body produces extra aggressive oxygen particles, also called reactive oxygen species (ROS). These particles can cause damage to cells and tissues in the intestine. This is called oxidative stress. This damage weakens the intestinal wall, making it easier for bacteria and other harmful substances to enter. This ensures that the immune system continues to respond and does not stop the inflammation - thus creating a negative vicious circle.¹³