Colitis, or inflammation of the colon, isn’t a single disease with a single cause. You can get it from an infection, an immune system malfunction, reduced blood flow, certain medications, or even radiation treatment. The type of colitis you develop depends entirely on what triggered the inflammation, and the causes range from eating contaminated food to taking common over-the-counter painkillers.
Infections: The Most Common Cause
Infectious colitis is the type most people encounter. Bacteria like Salmonella and E. coli are frequent culprits, and the usual route of exposure is contaminated food or water. Undercooked meat, unwashed produce, and unpasteurized dairy are classic sources. The infection inflames the colon lining, causing diarrhea, cramping, and sometimes bloody stool that typically resolves within days to a couple of weeks as your body clears the pathogen.
Antibiotics and C. diff Overgrowth
A bacterium called Clostridioides difficile (C. diff) already lives in your intestines in small numbers. Normally it’s kept in check by the other bacteria sharing the space. But when you take antibiotics, the drugs wipe out many of those competing bacteria, giving C. diff room to multiply rapidly. The overgrowth produces toxins that attack the colon lining, causing a particularly severe form of colitis called pseudomembranous colitis.
You’re up to 10 times more likely to develop a C. diff infection while taking antibiotics and in the month after finishing a course. Longer courses of antibiotics roughly double the risk again. This can happen with virtually any antibiotic, not just broad-spectrum ones. C. diff colitis is especially common in hospital and nursing home settings, where both antibiotic use and exposure to the bacterium are high.
Ulcerative Colitis: An Immune System Problem
Ulcerative colitis (UC) is one of the two main forms of inflammatory bowel disease, and it develops when your immune system attacks the lining of the colon by mistake. The inflammation typically starts in the rectum and can spread continuously through the large intestine. Unlike an infection, this type of colitis is chronic, meaning it involves recurring flares that alternate with periods of remission.
No single gene or trigger causes UC. Researchers have identified variations in dozens of genes that appear to play a role, many of them involved in the colon’s protective barrier function or in regulating immune cells called T cells. The current thinking is that a breakdown in the intestinal lining allows normal gut bacteria to contact deeper tissue, triggering an immune reaction that spirals out of control in genetically susceptible people. Environmental factors clearly matter too, since UC rates have risen sharply in industrialized countries over the past several decades.
One unusual wrinkle: smoking appears to be protective against ulcerative colitis. UC primarily affects nonsmokers and former smokers, and some evidence suggests that even childhood exposure to secondhand smoke reduces UC risk later in life. The opposite is true for Crohn’s disease, the other major form of inflammatory bowel disease, where smoking is a well-established risk factor. This paradox likely involves nicotine’s effects on immune function, mucus production, and blood flow in the colon, though the exact mechanism isn’t fully understood.
Reduced Blood Flow: Ischemic Colitis
Your colon needs a steady blood supply to stay healthy. When blood flow drops, the cells lining the colon are starved of oxygen, leading to damage and inflammation. This is ischemic colitis, and it tends to strike suddenly with cramping and bloody diarrhea, most often in adults over 60.
The causes are varied. Fatty deposits narrowing the arteries (atherosclerosis) is a common one, especially in people with high cholesterol or diabetes. Low blood pressure from dehydration, heart failure, or shock can also cut blood flow to the colon. Other risk factors include:
- Blood clotting disorders like factor V Leiden or sickle cell disease
- Abdominal surgery, where scar tissue can compress blood vessels
- Bowel obstruction from a hernia, tumor, or adhesions
- Cocaine or methamphetamine use, which constrict blood vessels
- Certain medications, including some heart drugs, migraine medicines, and hormone-based treatments like birth control pills
Medications That Inflame the Colon
Beyond antibiotics triggering C. diff, several common drug classes can directly cause colitis. Microscopic colitis, a form that can only be detected under a microscope, has strong associations with three types of widely used medications: NSAIDs (like ibuprofen and naproxen), proton pump inhibitors (acid reflux drugs), and SSRIs (a common class of antidepressants). In a large study, acid reflux drugs carried roughly a threefold increased risk, while NSAIDs and SSRIs each approximately doubled the risk. The strongest association was seen in people taking both NSAIDs and acid reflux drugs at the same time, which carried a fivefold increased risk.
Microscopic colitis typically causes chronic watery diarrhea without visible bleeding. It affects women far more often than men, with about 73% of cases occurring in women, and the average age at diagnosis is around 63.
Radiation Treatment
Radiation therapy directed at the pelvic area can damage the lining of the colon and rectum. This is most common after treatment for rectal, prostate, or cervical cancers. The risk increases with larger radiation fields, higher doses, prior pelvic surgery, or receiving chemotherapy at the same time as radiation. Symptoms can appear during treatment or develop months to years afterward.
Diet and Ultra-Processed Foods
Diet doesn’t cause colitis in the way an infection does, but it plays a meaningful role in triggering flares for people with inflammatory bowel disease. Multiple studies have found that high intake of ultra-processed foods is associated with active disease. In one cohort study, people with Crohn’s disease who ate more than 3.6 servings per day of ultra-processed foods had roughly a fourfold higher probability of relapse compared to those eating less. In ulcerative colitis, higher ultra-processed food intake has been linked to elevated markers of intestinal inflammation.
Specific food additives have also come under scrutiny. Carrageenan, a thickener found in many dairy and non-dairy products, triggered higher disease activity scores and increased inflammatory markers in one placebo-controlled trial of people with ulcerative colitis in remission. Ultra-processed meats showed the strongest association with active Crohn’s disease in cross-sectional data, followed by processed beverages, starches, and pastries. That said, trials that simply removed food additives from the diet have produced mixed results, so the relationship between specific additives and colitis is still being untangled.
Why the Type Matters
Knowing what caused the colitis determines what happens next. Infectious colitis from Salmonella usually clears on its own. C. diff colitis requires stopping the triggering antibiotic and often needs targeted treatment. Ischemic colitis may resolve with supportive care or, in severe cases, require surgery. Microscopic colitis often improves once the offending medication is stopped. And ulcerative colitis, being a chronic autoimmune condition, requires long-term management to control inflammation and prevent flares. The symptoms of these different types can overlap considerably, which is why identifying the underlying cause through stool tests, imaging, or colonoscopy is an essential first step.