Nine in ten people with ulcerative colitis experience rectal bleeding. Not occasional spotting – active, recurring blood loss that shows up in the toilet on an ordinary Tuesday morning. Yet surveys consistently show that most people with UC waited over a year before getting diagnosed, often because the early signs looked like something far more ordinary.
New medicines for conditions like ulcerative colitis are only made possible through clinical research volunteers, and the window to participate in studies testing tomorrow’s treatments is often limited. The symptoms below are the ones doctors and researchers look for first, and understanding them is the first step toward getting the right care.
Eli Lilly is currently running a Phase 2 clinical trial called EMERALD-3, designed specifically for adults with moderate to severe ulcerative colitis, testing a potential new oral treatment in a large, global, double-blind study against placebo over nearly two years of follow-up. Knowing exactly what ulcerative colitis looks like in the body – and in which specific ways it can escalate – is what makes that opportunity meaningful.
1. Bloody or Discolored Stools
According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), symptoms of UC may include diarrhea, passing blood, and abdominal pain. Of all those signs, blood in the stool tends to be the most alarming – and the most commonly minimized. People assume hemorrhoids, a dietary issue, or a rough week. They put off calling a doctor.
Ulcerative colitis is a chronic nonspecific inflammatory disease of the large intestine, characterized by continuous and diffuse inflammatory changes in colorectal mucosa. When that mucosa is inflamed, it bleeds. Symptoms include increased frequency of defecation, soft, mucous, and bloody feces, a feeling of urgent need to defecate, mucous discharge, nocturnal defecation, and incontinence.
The scale of this symptom is significant. By 2023, the global prevalence of UC was estimated at 5 million cases, with a sharp increase in global incidence. Among those affected, blood in the stool is nearly universal. In a 2025 study published in Egyptian Rheumatology and Rehabilitation, 90.9% of UC patients experienced rectal bleeding across 66 participants studied for both intestinal and extraintestinal disease manifestations. If you’re seeing blood consistently, this is not something to wait out.
2. Urgent, Uncontrollable Trips to the Bathroom
The urge to go right now – not in a few minutes, but immediately – is one of the ulcerative colitis signs that tends to disrupt daily life most severely. Lilly’s own research notes that for many people with UC, the unpredictable and immediate need to find a restroom can be stressful and disruptive to everyday activities.
The symptoms of ulcerative colitis can range from mild to severe and often develop gradually over time. Bowel urgency is among the most pervasive of those symptoms. Surveys of UC patients routinely report this as one of the most quality-of-life-damaging features of the disease – it affects travel, work, social plans, sleep, and mental health.
Some people with UC feel a frequent urge to go to the bathroom but find nothing is there – this is called rectal tenesmus, and up to 30% of people with ulcerative colitis experience it. The inflammation of the large bowel sends false signals to the nervous system, triggering urgency even when the bowel is empty. This cycle is one of the primary reasons UC patients in research studies report the most desire for better treatments.
3. Persistent Diarrhea
Diarrhea in UC isn’t simply an inconvenience. It’s the direct result of the inflamed colon losing its ability to absorb water normally. The NIDDK confirms that diarrhea is among the most common symptoms of ulcerative colitis alongside abdominal pain and rectal bleeding.
New medicines are made possible by clinical research volunteers in part because conditions like UC are so relentless. After 12 weeks, doctors in clinical trials check whether the signs and symptoms of ulcerative colitis have improved, using bowel frequency as one of the most measurable markers of disease activity.
Among UC patients, diarrhea is one of the most consistently reported symptoms, alongside urgency and bloody stool. About half of people with UC have mild symptoms during flare-ups, while others experience frequent fevers, bloody diarrhea, nausea, and severe abdominal cramps. The frequency and severity tend to track closely with how much of the colon is affected.
4. Abdominal Pain and Cramping
The cramping that comes with UC is distinct from ordinary stomach pain. It tends to concentrate in the lower left side of the abdomen and arrives in waves, often tied directly to the urge to use the bathroom. Abdominal pain in UC is typically localized in the left lower quadrant, particularly in cases of whole-colon involvement or toxic megacolon.
The NIDDK confirms that ulcerative colitis occurs when abnormal reactions of the immune system cause inflammation and ulcers in the lining of the large intestine. Those ulcers – open sores on the inner wall of the colon – are the direct source of much of the pain. As they develop, eating, moving, and digesting all become triggers for cramping.
Symptoms can vary depending on the extent of the inflammation and range from mild discomfort to severe, debilitating pain. For people with pancolitis (where the entire colon is affected), symptoms tend to be more severe and can include frequent, bloody diarrhea, significant abdominal pain, fatigue, and weight loss. Pain that is regular, located on the left side of the abdomen, and tied to bowel urgency warrants prompt evaluation.
5. Fatigue That Sleep Doesn’t Fix
Persistent inflammation places a significant burden on the body, leading to profound tiredness and lack of energy that can impact daily activities and work. This kind of fatigue is different from being tired after a long day. Several mechanisms drive it simultaneously: bleeding in the colon reduces red blood cell counts, nighttime bathroom trips interrupt sleep, and chronic diarrhea leads to dehydration – all of which compound into exhaustion that cannot be explained away by lifestyle alone.
Screening is required within 35 days prior to enrollment in UC clinical trials, partly because researchers need to establish a clear baseline of disease activity – including fatigue levels – before testing whether a new treatment produces improvement. Fatigue is now recognized as a primary endpoint in many modern UC studies precisely because it’s so debilitating for patients.
6. Unintended Weight Loss
Diarrhea, loss of appetite, and the inability to absorb calories from food can cause significant weight loss in people with UC. The NIDDK notes that UC symptoms may cause some people to lose their appetite and eat less, resulting in insufficient nutrients. Inflammation and general malaise can also lead to nausea, which reduces a person’s desire to eat, further contributing to potential nutritional deficiencies.
People with active UC often find themselves in a cycle where eating triggers symptoms, so they eat less, which accelerates nutrient deficiency and weight loss. Eli Lilly confirmed in March 2026 that their phase 3 study timeline for UC research will last approximately 4 – 5 years, which reflects how seriously the research community is treating the long-term burden of this disease. Unintentional weight loss in someone with known or suspected UC is a clinical red flag that typically accelerates the need for diagnosis and treatment evaluation.
7. Joint and Skin Problems
Extraintestinal manifestations – symptoms that appear outside the intestine – are a recognized feature of UC. The 2025 Egyptian Rheumatology and Rehabilitation study found that among 66 UC patients, 24 had peripheral arthropathy and 20 had inflammatory back pain, confirming that joint involvement is common rather than exceptional. Inflammation can affect the joints, leading to pain, stiffness, and swelling, particularly in larger joints like the knees, ankles, and hips.
A 2023 review in StatPearls published by the NIH found that extraintestinal manifestations are present in 10% to 30% of patients with ulcerative colitis, including episcleritis, uveitis, peripheral arthropathies, erythema nodosum, and pyoderma gangrenosum. Red, burning, or itchy eyes and painful bumps, rashes, or ulcers on the skin are also documented manifestations of UC in people with active disease. These symptoms can appear before bowel symptoms fully develop, which is one reason the diagnosis can be delayed.
Crucially, these manifestations can occur without any bowel symptoms being present at the time. For some patients, joint problems worsen during a flare but improve with treatment; others experience joint involvement even when bowel symptoms feel better.
When Severity Worsens
Not all UC is the same. In 2025, the American College of Gastroenterology published updated clinical guidelines on ulcerative colitis in adults that classify disease severity in concrete terms. Mild disease is defined as fewer than four bowel movements daily. Moderate and severe categories involve higher frequency, bleeding, systemic symptoms like fever, and markers of inflammation in the blood.
For participants in clinical trials, the total duration of study participation is typically about 69 weeks, including screening, which reflects how long it takes to fully evaluate whether a treatment moves someone from active disease toward sustained remission. Up to 15% of UC patients may also experience symptoms of severe disease, and severe UC can include life-threatening complications. Escalating severity is not inevitable, but it is common when disease management is delayed or inadequate.
Read More: How Often Should You Go to the Toilet? 7 Gut Health Facts
Inside the EMERALD-3 Study
If you’ve recognized several of the ulcerative colitis signs above in yourself, joining a clinical research study may be one of the most meaningful decisions you make – both for your own care and for others living with this disease.
Eli Lilly’s EMERALD-3 is a Phase 2 trial for adults with moderate to severe ulcerative colitis, testing an investigational oral drug called LY4268989 (also known as MORF-057) against placebo in a global, double-blind study. The drug is taken by mouth and is designed to calm gut inflammation and reduce flares, offering a potential alternative to injectable or infused treatments.
The planned duration is about 108 weeks per participant, which means the study is designed to evaluate both short-term symptom improvement and longer-term safety over nearly two full years. Key design elements and timelines were refined as recently as March 2026 before patient recruitment began. Participants can expect regular check-ins with medical staff, blood and stool tests to monitor inflammation, and structured assessments of how their symptoms are responding.
Clinical trials are voluntary at every step. Participants may ask questions at any time, take time before deciding to enroll, and withdraw from the study if they choose. Safety monitoring is rigorous throughout. Adverse events are closely tracked and reported in clinical trials of advanced therapies for ulcerative colitis, and data safety monitoring boards review participant data on an ongoing basis to ensure the process remains safe. The study team assesses how well the body is absorbing what it needs and whether inflammation is being controlled, using objective markers alongside symptom reports.
If you have moderate to severe UC and current treatments aren’t giving you adequate relief, this study may represent an opportunity to access a potential new therapy before it’s commercially available, under careful medical supervision. The EMERALD-3 trial enrollment page has full eligibility details and allows you to find a study site near you. Talking with your gastroenterologist before pre-screening is a sensible first step. The details of the trial can also be viewed at ClinicalTrials.gov.
What to Do Now
In UC clinical trials, doctors assess whether signs and symptoms have improved after a defined period – but that process only begins once someone takes the step of enrolling. If you’ve been living with rectal bleeding, persistent urgency, loose stools, abdominal cramping, or joint pain that your current treatment isn’t resolving, those are ulcerative colitis signs that deserve a fresh clinical conversation.
A successful oral therapy for ulcerative colitis could expand treatment options significantly for the large population of people managing this disease – and the only way to find out if LY4268989 works is for adults with active UC to participate in the study. Visit the EMERALD-3 study page at Lilly’s clinical trials portal to check eligibility criteria, browse trial sites, and take the first step. The page is built specifically to help you understand whether this study fits your situation – no commitment is required to pre-screen.
Ulcerative colitis has no cure and is a lifelong disorder with a significant impact on both physical and mental health. Staying active in your care, asking your doctor about every available option, and considering whether research participation is right for you are concrete steps that matter. The patients who benefit most from tomorrow’s breakthroughs are often the ones who chose to be part of finding them.
Disclaimer: The author is not a licensed medical professional. The information provided is for general informational and educational purposes only and is based on research from publicly available, reputable sources. It is not intended to constitute, and should not be relied upon as, medical advice, diagnosis, or treatment. Always consult a licensed physician or other qualified healthcare provider regarding any medical condition, symptoms, or medications. Do not disregard, avoid, or delay seeking professional medical advice or treatment because of information contained herein.
AI Disclaimer: This article was created with the assistance of AI tools and reviewed by a human editor.