What Is PUD? Causes, Symptoms, and Treatment

Peptic ulcer disease (PUD) is a condition in which open sores develop in the lining of the stomach or the upper part of the small intestine (the duodenum). The two major culprits behind most cases are infection with a bacterium called Helicobacter pylori and regular use of common painkillers like ibuprofen and aspirin. Globally, PUD affected roughly 8 million people as of 2019, and while that number has risen in absolute terms due to population growth, the rate per person has actually fallen over the past few decades. Despite being treatable and even preventable, ulcers remain a source of real suffering and, when complications arise, genuine danger.

How an Ulcer Forms

Your stomach produces hydrochloric acid and an enzyme called pepsin to break down food. That acid is strong enough to damage tissue, so the stomach and duodenum rely on a built-in defense system: a layer of mucus gel coats the lining, and cells beneath that gel secrete bicarbonate, which neutralizes acid right at the surface. This creates a thin zone of near-neutral pH between the corrosive acid in the stomach cavity and the delicate cells underneath.1PubMed. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin Pepsin, meanwhile, is kept at bay by the mucus gel itself, which acts as a physical barrier the enzyme cannot easily penetrate.

An ulcer forms when something disrupts this balance. In people with PUD, the proportion of a particularly aggressive form of pepsin (pepsin type 1) in gastric juice is four to five times higher than normal, and the protective mucus layer in the area near the ulcer is structurally weakened.2PubMed. Pepsins and the mucus barrier in peptic ulcer disease Once the mucus barrier breaks down, acid and pepsin reach the underlying tissue, and the result is an erosion that deepens into an ulcer. The old clinical saying captures the idea neatly: “no acid, no pepsin, no ulcer.”

The Two Main Causes

H. pylori Infection

H. pylori is a spiral-shaped bacterium uniquely adapted to survive in the acidic environment of the stomach. It burrows into the mucus layer, triggers chronic inflammation, and over time weakens the mucosal defense. The pattern of inflammation matters: when the infection causes widespread inflammation without significant tissue thinning, duodenal ulcers tend to result; when the inflammation leads to thinning (atrophy) of the stomach lining, gastric ulcers or even stomach cancer become more likely.3PubMed Central. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer In one hospital-based study of patients presenting with upper gastrointestinal bleeding, about two-thirds had ulcers tied to H. pylori alone, and another 11% had ulcers linked to both H. pylori and painkiller use.4PubMed Central. Non-Helicobacter pylori, non-NSAIDs peptic ulcers: a descriptive study on patients referred to Taleghani hospital with upper gastrointestinal bleeding

NSAIDs

Nonsteroidal anti-inflammatory drugs, the class that includes ibuprofen, naproxen, and aspirin, are the other major cause. These drugs work by blocking enzymes called COX-1 and COX-2. The catch is that COX-1 also helps produce prostaglandins that protect the stomach lining, stimulating mucus and bicarbonate secretion and maintaining blood flow to the tissue.5PubMed. Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself? When you take an NSAID, you suppress pain and inflammation elsewhere in the body, but you also reduce the stomach’s ability to defend itself.6PubMed Central. Effects of Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Gastroprotective NSAIDs on the Gastrointestinal Tract: A Narrative Review Occasional use rarely causes problems in otherwise healthy people, but chronic daily use, especially in older adults or those with a history of ulcers, raises the risk substantially.

Rare and Overlooked Causes

Not every ulcer traces back to H. pylori or NSAIDs. In that same hospital study, about 13% of bleeding ulcer patients had neither cause identified.4PubMed Central. Non-Helicobacter pylori, non-NSAIDs peptic ulcers: a descriptive study on patients referred to Taleghani hospital with upper gastrointestinal bleeding These “idiopathic” ulcers pose a clinical puzzle because there is no clear target to treat and no established way to prevent recurrence.7PubMed Central. Helicobacter pylori-negative, non-steroidal anti-inflammatory drug: negative idiopathic ulcers in Asia Another uncommon cause is Zollinger-Ellison syndrome, in which a tumor (gastrinoma) secretes massive amounts of the hormone gastrin, flooding the stomach with acid. These tumors are often malignant, and a significant proportion of patients already have metastatic disease by the time they are diagnosed.8Radiology Case Reports. Zollinger-Ellison syndrome: Revelation of the gastrinoma triangle Other less common contributors include heavy alcohol use, severe physiological stress (such as being in an intensive care unit), and certain other medications like corticosteroids when combined with NSAIDs.

Risk Factors Beyond the Usual Suspects

Smoking and being overweight both appear to independently raise your odds of developing an ulcer. A genetic analysis that used a method designed to tease out cause-and-effect found that a genetic predisposition to smoking was associated with increased risk of both gastric and duodenal ulcers, and higher body mass index showed a similar pattern.9PubMed Central. Smoking, alcohol consumption, diabetes, body mass index, and peptic ulcer risk: A two-sample Mendelian randomization study Interestingly, that same analysis did not find a clear causal link between alcohol consumption or type 2 diabetes and ulcer risk, which goes against what many people assume. Smoking likely worsens ulcers through several routes: it increases acid secretion, impairs blood flow to the stomach lining, and slows the healing of existing ulcers. If you smoke and have a confirmed ulcer, quitting is one of the most straightforward things you can do to help it heal.

What an Ulcer Feels Like

The classic symptom is a burning or gnawing pain in the upper abdomen, between the navel and the breastbone. But the timing and triggers differ depending on where the ulcer sits. Duodenal ulcers tend to hurt several hours after eating, often waking people in the middle of the night. Eating something usually brings relief, at least temporarily, because food buffers the acid. Gastric ulcers behave differently: eating tends to make the pain worse, not better, and the discomfort may radiate to the back.10Digestive Diseases. Chronic Abdominal Pain: Gastroenterologist Approach

Many people with ulcers also experience bloating, nausea, a sense of fullness after small meals, or loss of appetite. Some ulcers produce no noticeable symptoms at all, which is why they occasionally get discovered only when a complication occurs. If you notice dark, tarry stools, vomit that looks like coffee grounds, or experience sudden severe abdominal pain, those are warning signs of a complication and warrant urgent medical attention.

How Ulcers Are Diagnosed

The most reliable way to diagnose PUD is upper endoscopy, where a thin, flexible camera is passed through the mouth into the stomach and duodenum. This lets the doctor see the ulcer directly, take biopsies if needed, and test for H. pylori at the same time. Biopsy-based tests for the bacterium tend to be highly specific, meaning that if the test says H. pylori is there, it almost certainly is. However, in patients who are actively bleeding, the sensitivity of individual tests drops, and combining more than one testing method improves the chances of catching the infection.11PubMed Central. Accuracy of the Helicobacter pylori diagnostic tests in patients with peptic ulcer bleeding: a systematic review and network meta-analysis Non-invasive options for detecting H. pylori include a urea breath test and a stool antigen test, both of which are accurate and widely used when endoscopy is not immediately necessary.

For younger patients with typical ulcer symptoms and no alarm signs (like weight loss, difficulty swallowing, or anemia), many guidelines allow a “test and treat” approach: test for H. pylori noninvasively, and if positive, treat without endoscopy first. Endoscopy is generally recommended for anyone over 50 or 55 with new symptoms, anyone with alarm features, and anyone whose symptoms persist despite treatment.

Treatment

Acid Suppression

Proton pump inhibitors (PPIs) like omeprazole, lansoprazole, and esomeprazole are the cornerstone of ulcer treatment. They shut down the acid pumps in the stomach lining, dramatically reducing acid output and giving the ulcer a chance to heal. PPIs are effective for both uncomplicated and complicated ulcers, and most ulcers heal within four to eight weeks on standard doses.12PubMed Central. 25 Years of Proton Pump Inhibitors: A Comprehensive Review One practical quirk: PPIs work best when taken 30 to 60 minutes before a meal, because they only block acid pumps that are actively working. Some people experience breakthrough symptoms, especially at night, if the timing is off.

Eradicating H. pylori

If H. pylori is detected, killing the bacterium is critical. Without eradication, ulcers recur at high rates. The treatment regimens have evolved because the bacterium has become increasingly resistant to common antibiotics, particularly clarithromycin.13Gastroenterology. Reconciliation of Recent Helicobacter pylori Treatment Guidelines in a Time of Increasing Resistance to Antibiotics Current guidelines in many regions now recommend bismuth quadruple therapy as a first-line option: a PPI, bismuth subsalicylate, and two antibiotics (typically metronidazole and tetracycline), taken for 14 days.14PubMed Central. Development of Helicobacter pylori treatment: How do we manage antimicrobial resistance? In areas where clarithromycin resistance is still low, clarithromycin-based triple therapy remains an option. The regimen your doctor chooses should ideally be guided by local resistance patterns or, better yet, by susceptibility testing of the specific strain you carry.

Managing NSAID-Related Ulcers

For ulcers caused by NSAIDs, the first step is straightforward: stop the NSAID if possible. If you need to keep taking a painkiller for a chronic condition like arthritis, the strategy shifts toward protection. PPIs taken alongside the NSAID reduce ulcer risk considerably. Switching to a COX-2 selective inhibitor (like celecoxib), which spares COX-1 and thus the stomach’s protective prostaglandins, is another option. For people at the highest risk, such as those with a history of ulcer bleeding, combining a COX-2 inhibitor with a PPI appears to offer the greatest gastrointestinal safety.15PubMed Central. Prevention of NSAID-induced gastroduodenal ulcers Misoprostol, a synthetic prostaglandin, is another preventive option and was shown in direct comparison to be more effective than sucralfate (a mucosal-coating drug) at preventing NSAID-related gastric ulcers.16PubMed. Prevention of nonsteroidal anti-inflammatory drug-induced gastroduodenal ulcers: role of mucosal protective and gastric antisecretory drugs Misoprostol can cause diarrhea and cramping, though, so it is not always well tolerated.

When Things Go Wrong

Most ulcers heal without serious trouble if treated, but untreated or poorly controlled ulcers can lead to three major complications:

Surgery for PUD Today

Before effective acid-suppressing drugs and H. pylori eradication therapy existed, surgery to reduce acid production (like vagotomy or partial gastrectomy) was a mainstay of ulcer treatment. Today, surgery is almost exclusively reserved for complications. In perforation cases, simple closure of the hole, often with an omental patch, is sufficient in the large majority of patients. Both open and laparoscopic approaches are used, and definitive acid-reducing surgery is no longer considered justified during emergency repair.17PubMed. Surgical management of peptic ulcer disease today–indication, technique and outcome For large or “giant” perforations, more complex techniques may be needed.20Current Surgery Reports. Surgical Management of Perforated Peptic Ulcers For bleeding ulcers that endoscopy cannot control, surgeons can directly suture the bleeding site or ligate the supplying artery.

Ulcers at the Extremes of Age

PUD is not just a middle-aged adult’s disease. In children, H. pylori infection can cause ulcers, but the approach to testing and treating differs. Children have a limited selection of antibiotics that are both safe and effective for them, a higher rate of reinfection, and in some cases, the infection clears on its own.21PubMed Central. Diagnosis and treatment of Helicobacter pylori infections in children and elderly populations Because of that spontaneous clearance, most guidelines recommend against testing and treating children unless they have clear ulcer symptoms or a confirmed ulcer, rather than screening broadly.

In elderly patients, the challenges are different. They are more likely to be on NSAIDs for arthritis, more likely to be on aspirin or blood thinners for heart disease, and more likely to have silent ulcers that present only when a complication strikes. They also tend to tolerate the multi-drug eradication regimens less well, experiencing more side effects from the antibiotics and the PPIs. Drug interactions are a particular concern in older adults who already take multiple medications. Doctors managing PUD in elderly patients typically need to balance the benefit of eradicating H. pylori against the realistic burden of a 14-day regimen with four drugs.

The Changing Landscape of PUD

The epidemiology of peptic ulcer disease has shifted considerably over the past century. In 2019, the global age-standardized prevalence rate was about 99 per 100,000 people, down from roughly 143 per 100,000 in 1990.22PubMed Central. The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study Much of this decline reflects improvements in sanitation, falling H. pylori infection rates in younger generations, and the availability of PPIs. Duodenal ulcers in particular have become less common in Western populations, while the incidence of gastric ulcers has remained more stable.23PubMed Central. Incidence of duodenal ulcers and gastric ulcers in a Western population: back to where it started

That said, PUD has not disappeared, and in some ways the remaining cases are harder to manage. As H. pylori rates fall, the proportion of ulcers caused by NSAIDs, by other medications, or by unknown causes grows. Antibiotic resistance in the H. pylori strains that do persist makes eradication more difficult and sometimes requires multiple treatment attempts. The disease has evolved from a common condition with a single dominant cause into a more heterogeneous one where the treatment plan depends heavily on the specific situation.

Diet, the Gut Microbiome, and Complementary Approaches

For decades, people with ulcers were told to eat bland diets and drink milk. That advice has been largely abandoned because there is little evidence it helps and because milk actually stimulates acid secretion. The modern understanding is more nuanced. Diets high in fiber, polyphenol-rich foods (like berries and green tea), omega-3 fatty acids, and fermented foods appear to support a gut bacterial environment that may be less hospitable to H. pylori.24PubMed. Probiotics and Diet Modifications: A Holistic Approach to Tackling Helicobacter pylori with the Help of the Gut Microbiota This is not a substitute for medical treatment, but it is a reasonable complementary strategy.

Probiotics have attracted growing interest. Certain strains produce compounds that inhibit H. pylori growth and can modulate immune responses in ways that support eradication. Standard eradication therapy itself, which involves a PPI and two or more antibiotics, disrupts the broader gut microbiome, and natural supplements including probiotics may help with recovery of that microbial balance.25Journal of Drug Delivery and Therapeutics. Exploring the Gut Microbiome’s Influence on Peptic Ulcer Disease: Mechanistic Insights, Pharmacological Implications, and Emerging Therapeutic Strategies Some clinical trials have added probiotics to standard eradication regimens and reported modestly improved eradication rates and fewer antibiotic side effects, though the evidence is not yet strong enough for probiotics to be included in most official guidelines. Curcumin and ginger have also shown preliminary promise in supporting ulcer healing, but human trial data remain limited. If you want to try these approaches, they work best as additions to, not replacements for, proven medical therapy.

Ulcers with No Clear Cause

The small but meaningful subset of ulcers that test negative for both H. pylori and NSAID use presents a genuine clinical challenge. In a study of patients presenting with upper GI bleeding, about 13% fell into this category, and those patients were more likely to have coexisting medical conditions.4PubMed Central. Non-Helicobacter pylori, non-NSAIDs peptic ulcers: a descriptive study on patients referred to Taleghani hospital with upper gastrointestinal bleeding Without an identifiable cause, there is no targeted fix. These patients typically receive long-term PPI therapy to keep acid levels low, but there is no effective strategy to prevent recurrence the way eradicating H. pylori prevents recurrence of bacterial ulcers.7PubMed Central. Helicobacter pylori-negative, non-steroidal anti-inflammatory drug: negative idiopathic ulcers in Asia Part of the puzzle is that some of these cases may involve undetected NSAID or aspirin use (over-the-counter painkillers people forget to mention), surreptitious use of other ulcer-causing drugs, or rare conditions like Crohn’s disease affecting the upper GI tract. When an ulcer keeps coming back despite appropriate treatment and no obvious cause, a careful workup for unusual etiologies becomes essential.