Introduction
If you've been diagnosed with ulcerative colitis (UC), one of the first questions you probably asked was: why me? The honest answer is that researchers still can't point to a single cause. UC develops from a collision of genetic susceptibility, immune system malfunction, gut microbiome disruption, and environmental exposures. But that doesn't mean the science is a dead end. Over the past decade, the picture has sharpened considerably, and understanding the contributing factors can help you make sense of your diagnosis, assess family risk, and focus on the variables you can actually influence.
Your Immune System Turns on Your Own Tissue
Ulcerative colitis is classified as an autoimmune-related condition. In a healthy gut, the immune system tolerates the trillions of bacteria living in the colon. In UC, that tolerance breaks down. The immune system mistakes the lining of the colon for a threat and launches a sustained inflammatory attack.
The specific mechanisms involve an imbalance in T-cell activity. In UC patients, certain T-cell subsets (particularly Th2 and Th9 cells) become overactive and flood the colon lining with pro-inflammatory cytokines like TNF-alpha and interleukins. At the same time, regulatory T cells that normally suppress inflammation lose ground. The result is chronic, relapsing inflammation that damages the mucosal barrier of the colon.
This barrier damage creates a vicious cycle. Once the intestinal lining is compromised, bacteria that normally stay in the gut lumen can penetrate deeper tissue layers, triggering further immune activation through toll-like receptor signaling and neutrophil recruitment. The inflammation feeds on itself.
Genetics Load the Gun
UC has a clear genetic component, though it's far from deterministic. According to MedlinePlus, people with a first-degree relative who has inflammatory bowel disease (IBD) are four to eight times more likely to develop some form of it themselves. Roughly 10% to 25% of UC patients have a parent or sibling with IBD.
Genome-wide association studies have identified more than 240 genetic loci linked to IBD, and about 67% of those are shared between UC and Crohn's disease. Many of the implicated genes relate to immune regulation, epithelial barrier function, and microbial sensing. Genes like ECM1, CDH1, and HNF4-alpha, which are involved in maintaining the mucosal barrier, appear to confer specific risk for UC.
But genetics alone don't seal your fate. Most people who carry UC-associated gene variants never develop the disease, and many UC patients have no family history at all. Genes create vulnerability. Something else pulls the trigger.
The Gut Microbiome Is Out of Balance
One of the most consistent findings in UC research is that patients have a disrupted gut microbiome, a state called dysbiosis. Compared to healthy individuals, people with UC tend to have fewer beneficial bacterial species (like Faecalibacterium prausnitzii and Bifidobacterium longum) and higher levels of potentially harmful bacteria.
These microbial shifts matter because gut bacteria play a direct role in immune regulation. Beneficial bacteria help expand regulatory T cells that keep inflammation in check and produce short-chain fatty acids that nourish the colon lining. When these populations decline, the immune system loses a critical check on inflammatory signaling.
Whether dysbiosis causes UC or results from it remains an active area of investigation. The most likely answer is both: genetic and environmental factors create conditions for dysbiosis, and once established, the altered microbiome perpetuates the inflammatory cycle.
Environmental Factors and the Westernization Effect
If UC were purely genetic, its incidence would stay relatively stable over time. Instead, rates have climbed steadily in industrialized nations over the past century and are now rising rapidly in newly industrializing countries across South America, Eastern Europe, Asia, and Africa. This pattern strongly implicates environmental factors tied to modern, urbanized living.
Researchers have identified several environmental exposures that correlate with increased UC risk. Diet is among the most studied. The Western dietary pattern, heavy in ultra-processed foods, refined sugars, red meat, and saturated fats, has been linked to increased UC risk and symptom severity. Food additives like emulsifiers, carrageenan, and artificial sweeteners may disrupt gut barrier function and microbial balance. One analysis of six cohorts from the U.S. and Europe found that adherence to healthy lifestyle behaviors (including eating sufficient fruits, vegetables, and fiber) could potentially prevent around 50% of UC cases.
Air pollution, reduced breastfeeding, and improved sanitation (which limits early microbial exposure) have also been flagged as contributing factors. The overarching theory is that modern environments alter the gut microbiome and immune development in ways that increase susceptibility to conditions like UC.
Medications That May Increase Risk
Two common medication classes deserve attention in the UC conversation.
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen have been associated with UC flares, though the evidence is somewhat mixed. Some studies show a meaningful increase in flare risk within the first two weeks after NSAID use, while others suggest confounding factors may explain the association. Regardless of the debate, most gastroenterologists advise UC patients to use NSAIDs with caution and prefer acetaminophen when possible.
Antibiotics are a clearer concern. Research published in the Journal of Crohn's and Colitis found that specific antibiotics significantly increased the risk of IBD flare-ups. Antibiotic exposure has also been associated with increased risk of developing IBD in the first place, particularly in people over 40. The mechanism likely involves disruption of the gut microbiome, which, as noted above, plays a central role in immune regulation.
Stress Doesn't Cause UC, but It Fuels Flares
Stress is one of the most commonly cited triggers among UC patients, and the science supports the connection, though with an important caveat: psychological stress does not cause UC. It can, however, contribute to the first expression of the disease in someone who is already genetically and immunologically primed, and it reliably increases the risk of clinical flares in people with established disease.
The mechanism runs through the gut-brain axis. Under chronic stress, the body activates the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system, which can increase intestinal permeability, shift the gut microbiome, and amplify inflammatory signaling in the colon. Research from the Crohn's & Colitis Foundation has identified specific microbial signatures associated with high stress reactivity and increased flare risk, suggesting that a patient's microbiome may determine how vulnerable they are to stress-induced disease activity.
Two Surprising Protective Factors
UC research has produced two genuinely counterintuitive findings.
The first involves smoking. While cigarette smoking increases the risk of Crohn's disease and nearly every other chronic condition, it is consistently associated with a reduced risk of UC. Nicotine appears to modulate mucosal immune responses, reduce inflammatory cell recruitment, and increase the thickness of protective colonic mucus. Researchers have studied nicotine patches and enemas as potential therapies, but side effects have limited clinical usefulness. This is an observation with scientific value, not a treatment recommendation: the health risks of smoking far outweigh any protective effect against UC.
The second involves appendectomy. Removal of the appendix, specifically for appendicitis before age 20, is associated with a significantly reduced risk of developing UC later in life. Among patients who already have UC, prior appendectomy is linked to lower colectomy rates and milder disease courses. A recent clinical trial published in The Lancet Gastroenterology & Hepatology found that appendectomy was superior to standard medical therapy alone for maintaining UC remission. The appendix contains immune tissue that may play a role in driving colonic inflammation in susceptible individuals.
What This Means for You
UC isn't caused by any one thing. It emerges from a combination of inherited genetic risk, immune system dysfunction, microbiome disruption, and environmental exposures that converge in the gut. You didn't do something wrong to get this disease, and no single lifestyle change would have prevented it.
What you can do is focus on the modifiable factors. Dietary choices, stress management, medication awareness, and microbiome health are all areas where your daily decisions interact with your disease. Tracking how your body responds to specific foods, stressors, and exposures over time can help you identify patterns that are unique to your disease, patterns that population-level research can't capture. Tools like Aidy can help you log symptoms alongside potential triggers, so you can move from general knowledge about UC causes to specific insight about what drives your flares.