Peptic Ulcer Disease: What Causes It and How Antibiotics and Acid Reducers Really Work

Most people think stomach ulcers are caused by stress or too much spicy food. That’s what we were told for decades. But here’s the truth: peptic ulcer disease is mostly caused by two things you can’t control - a bacteria called Helicobacter pylori or daily use of common painkillers like ibuprofen or aspirin. And the good news? It’s one of the most treatable digestive conditions out there.

What Actually Causes a Peptic Ulcer?

A peptic ulcer isn’t just a sore in your stomach. It’s a deep break in the lining of your stomach or the first part of your small intestine (duodenum). This lining normally protects itself from stomach acid. But when that protection breaks down, acid eats away at the tissue, causing pain and sometimes serious bleeding.

The two biggest culprits are clear from decades of research:

• Helicobacter pylori (H. pylori) - This spiral-shaped bacteria lives in the stomach lining of over half the world’s population. It doesn’t cause problems for most people. But in some, it triggers inflammation, weakens the mucus barrier, and lets acid damage the tissue underneath. It’s found in more than 50% of duodenal ulcers and 30-50% of gastric ulcers.
• NSAIDs - These are nonsteroidal anti-inflammatory drugs like ibuprofen (Advil), naproxen (Aleve), and aspirin. They’re used for headaches, arthritis, and muscle pain. But they block protective chemicals in the stomach lining. Over time, especially with daily use, they can cause ulcers. Today, NSAIDs cause more than half of all peptic ulcers, especially in older adults who take them long-term for chronic pain.

How Do You Know If You Have One?

Symptoms can be mild or severe. Many people ignore them at first, thinking it’s just indigestion.

Common signs include:

• A burning or gnawing pain in the upper belly, often between meals or at night
• Pain that gets better after eating or taking antacids
• Feeling full too quickly, bloating, or nausea
• Losing appetite or unexplained weight loss
• Heartburn or a sour taste in the mouth

If you see any of these warning signs, don’t wait:

• Vomiting blood - looks like coffee grounds
• Black, tarry stools - a sign of digested blood
• Sudden, sharp abdominal pain that doesn’t go away

These mean your ulcer may be bleeding or perforating. That’s an emergency.

How Is It Diagnosed?

You can’t diagnose a peptic ulcer just by symptoms. Doctors need proof.

The gold standard is an upper endoscopy. A thin, flexible tube with a camera goes down your throat to look directly at your stomach and duodenum. If there’s an ulcer, they can take a small tissue sample to test for H. pylori.

Other tests include:

• Stool antigen test - Checks for H. pylori proteins in your poop. Fast, accurate, and non-invasive.
• Breath test - You drink a special solution. If H. pylori is present, it breaks it down and releases carbon dioxide you breathe out. They measure it with a device.
• Blood test - Looks for antibodies to H. pylori. But it can’t tell if you have an active infection or just had one in the past.

Antibiotics: The Real Cure for H. pylori

If H. pylori is the cause, antibiotics are the only way to get rid of it for good. But you don’t just take one antibiotic. You take two - plus a stomach acid reducer.

The standard treatment is called triple therapy: two antibiotics + one proton pump inhibitor (PPI), taken for 7 to 14 days.

Common antibiotic combinations include:

• Amoxicillin + clarithromycin
• Metronidazole + clarithromycin
• Amoxicillin + metronidazole

The PPI - like omeprazole or esomeprazole - helps by lowering stomach acid. That lets the antibiotics work better and gives your lining time to heal.

But here’s the catch: antibiotic resistance is rising. In the U.S., about 35% of H. pylori strains are now resistant to clarithromycin. That means triple therapy fails in up to 20% of cases.

That’s why newer guidelines (from the American College of Gastroenterology, 2022) now recommend quadruple therapy as first-line in areas with high resistance. This adds bismuth (like Pepto-Bismol) to the mix, making it four medications for 10-14 days. It’s more pills, more side effects - but it works better when resistance is common.

Proton Pump Inhibitors: The Acid Reducers That Heal

PPIs are the backbone of ulcer treatment - whether H. pylori is involved or not.

They work by shutting down the acid pumps in your stomach cells. Unlike older H2 blockers (like famotidine), PPIs reduce acid for 24-72 hours per dose. That’s why they’re the go-to for healing ulcers.

Common PPIs include:

• Omeprazole (Prilosec)
• Esomeprazole (Nexium)
• Lansoprazole (Prevacid)
• Pantoprazole (Protonix)
• Rabeprazole (AcipHex)

You need to take them 30-60 minutes before a meal - usually breakfast. That’s when your stomach starts pumping out acid. Taking them on an empty stomach lets the drug reach the pumps before they turn on.

For H. pylori ulcers, you take the PPI for 4-8 weeks after antibiotics. For NSAID ulcers, you might need it longer - sometimes indefinitely - if you can’t stop the painkillers.

What About NSAID-Induced Ulcers?

If your ulcer is from ibuprofen or aspirin, the first step is simple: stop using them - if you can.

But many people with arthritis or heart disease can’t just quit. So doctors have two options:

• Switch to a safer painkiller - Acetaminophen (Tylenol) doesn’t harm the stomach lining. It’s the best alternative for chronic pain.
• Keep the NSAID, but protect your stomach - That means taking a PPI daily, or sometimes misoprostol (a prostaglandin analog). Misoprostol helps rebuild the stomach’s natural defenses, but it can cause diarrhea and isn’t safe during pregnancy.

What Happens If It Doesn’t Heal?

About 10-15% of ulcers don’t respond to standard treatment. These are called refractory ulcers. The top reasons:

• You didn’t finish your antibiotics - even missing one dose can let H. pylori come back
• You kept taking NSAIDs
• You’re still smoking - smoking doubles your risk of ulcers and slows healing
• You have antibiotic-resistant H. pylori
• You have another condition like Zollinger-Ellison syndrome (rare, but causes extreme acid production)

If your ulcer doesn’t heal, your doctor will likely repeat the endoscopy and test for resistance. Newer drugs like vonoprazan - approved in the U.S. in January 2023 - are showing 90% success rates in eradicating H. pylori, even in resistant cases. It’s not yet first-line everywhere, but it’s changing the game.

Side Effects and Long-Term Risks

PPIs work well - but they’re not harmless.

Short-term side effects from antibiotics include:

• Metallic taste (common with metronidazole)
• Diarrhea or nausea
• Headaches
• Yeast infections

Long-term PPI use (more than a year) has been linked to:

• Lower vitamin B12 levels - because acid helps absorb it
• Increased risk of bone fractures - especially in older adults
• Higher chance of C. diff infection - a dangerous gut bug
• Rebound acid reflux - when you stop PPIs suddenly, your stomach overproduces acid for weeks

That’s why doctors now recommend the lowest effective dose for the shortest time. Don’t take PPIs daily unless you need them.

Lifestyle Changes That Actually Help

Medication fixes the cause. But your habits decide if it comes back.

• Quit smoking - It increases ulcer risk by 2-3 times and slows healing by 40%
• Limit alcohol - More than 3 drinks a day increases ulcer risk by 300%
• Avoid NSAIDs - Use acetaminophen instead for pain
• Eat regular meals - Skipping meals lets acid build up
• Don’t lie down after eating - Wait 2-3 hours to reduce reflux

What’s Next for Peptic Ulcer Treatment?

The future is personalized.

By 2025, 60% of H. pylori treatments in the U.S. are expected to include antibiotic resistance testing. Instead of guessing which drugs to use, your doctor will test your bacteria first - then pick the antibiotics that will actually work.

Vonoprazan is gaining traction. It’s faster, stronger, and works even when acid levels are high. It’s already standard in Japan and now available in the U.S.

And while H. pylori rates are dropping in wealthy countries (down from 60% in 1980 to 25% today), NSAID ulcers are rising. Why? More older adults with arthritis, more people taking daily painkillers.

So even as we get better at killing bacteria, we still need smarter ways to protect stomachs from the medicines we rely on.

Frequently Asked Questions