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

Most people think stomach ulcers are caused by stress or spicy food. That’s what we were told for decades. But here’s the truth: peptic ulcer disease is mostly caused by a bacteria you can’t see and painkillers you probably take without thinking. And the good news? It’s one of the most treatable conditions in gastroenterology-if you know what to do.

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 fails, acid eats through, causing pain, bleeding, and sometimes serious complications.

There are two main culprits. The first is Helicobacter pylori (H. pylori), a spiral-shaped bacteria that lives in the stomach. It was discovered in 1982 by two Australian doctors, Barry Marshall and Robin Warren, who proved it wasn’t just a bystander-it was the cause. They even drank a culture of it to prove their theory. Marshall got sick. They won the Nobel Prize in 2005. Today, H. pylori is found in over half of all duodenal ulcers and 30-50% of gastric ulcers.

The second major cause? NSAIDs. That’s nonsteroidal anti-inflammatory drugs: ibuprofen, naproxen, aspirin. These are the go-to painkillers for headaches, back pain, arthritis. But they block protective chemicals in the stomach lining. In fact, NSAIDs now cause more ulcers than H. pylori in many places, especially among older adults who take them daily. If you’re over 60 and take ibuprofen every day for knee pain, you’re at higher risk.

Stress and spicy food? They don’t cause ulcers. But they can make them worse. Smoking doubles or triples your risk. Drinking more than three alcoholic drinks a day increases it by 300%. So while they’re not the root cause, they’re still dangerous partners in crime.

How Do You Know You Have One?

The classic sign is a burning or gnawing pain in your upper belly, right below the breastbone. It often comes between meals or at night. Some people say it feels better after eating-then comes back a couple hours later. That’s because food temporarily buffers the acid against the ulcer.

Other signs include:

• Feeling full too fast
• Nausea or vomiting
• Intolerance to fatty or greasy foods
• Bloating or belching

But here’s the danger zone: if you start vomiting blood (looks like coffee grounds), passing black, tarry stools, or losing weight without trying, you need help right away. These mean bleeding or a perforation-both medical emergencies.

The only way to confirm an ulcer? An endoscopy. A thin camera is passed down your throat to look directly at the ulcer. During the procedure, doctors also take samples to test for H. pylori. Blood, breath, and stool tests can detect the bacteria too, but endoscopy gives you the full picture.

Antibiotics: How They Erase H. pylori

If H. pylori is the cause, antibiotics are the solution. But not just one. You need a combo. The old standard was triple therapy: two antibiotics plus a proton pump inhibitor (PPI) for 7-14 days.

Common combinations include:

• Amoxicillin + clarithromycin + omeprazole
• Metronidazole + clarithromycin + lansoprazole
• Amoxicillin + metronidazole + pantoprazole

You’ll be taking 3-4 pills, 2-3 times a day. It’s a lot. And it’s messy. Many people report a strong metallic taste with metronidazole. Others get diarrhea, nausea, or a weird aftertaste. But sticking to the full course is non-negotiable. If you skip even one dose, you risk leaving behind resistant bacteria. That makes the next round harder-and less effective.

Here’s the payoff: when H. pylori is fully cleared, the chance of the ulcer coming back drops from 70% to under 10%. That’s the difference between a chronic problem and a one-time fix.

But here’s the twist: clarithromycin resistance is rising. In the U.S., over 35% of H. pylori strains are now resistant to it. That’s why new guidelines from the American College of Gastroenterology (2022) now recommend quadruple therapy as first-line in many areas. That means adding bismuth (like Pepto-Bismol) to the mix: two antibiotics, bismuth, and a PPI. It’s more pills, more side effects, but it works better where resistance is high.

And there’s a new player: vonoprazan. Approved in the U.S. in January 2023, it’s not a PPI. It’s a potassium-competitive acid blocker. It shuts down acid production faster and more completely. In Japan, it cleared H. pylori in 90% of cases-higher than traditional PPIs. It’s not yet widely used, but it’s the future.

Acid-Reducing Medications: PPIs vs. H2 Blockers

Antibiotics kill the bacteria. But acid-reducing meds give your stomach time to heal. That’s where proton pump inhibitors (PPIs) come in.

PPIs like omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), and lansoprazole (Prevacid) block the final step of acid production. One dose lasts 24-72 hours. That’s why they’re the gold standard. They heal ulcers faster than anything else.

H2 blockers-like famotidine (Pepcid), cimetidine (Tagamet), and nizatidine (Axid)-work too, but they’re weaker. They only block about half the acid and last 10-12 hours. They’re fine for mild heartburn, but not for healing ulcers.

Timing matters. PPIs must be taken 30-60 minutes before a meal. That’s when your stomach’s acid pumps are waking up. Take them after eating? They’re less effective.

But there’s a catch. Long-term PPI use has risks. The FDA has issued warnings about:

• Increased risk of bone fractures with high doses over a year
• Lower vitamin B12 levels (because acid helps absorb it)
• Higher chance of C. difficile infection (a serious gut bug)
• Rebound acid hypersecretion-your stomach overproduces acid when you stop

That last one trips people up. They feel worse after stopping PPIs and think the ulcer’s back. It’s not. It’s your body overcompensating. That’s why doctors recommend tapering off slowly, not quitting cold turkey.

What If You Need NSAIDs?

If you have arthritis, back pain, or heart disease and need daily NSAIDs, you can’t just stop. So what do you do?

Option one: switch to COX-2 inhibitors like celecoxib (Celebrex). They’re gentler on the stomach, but not risk-free. Option two: take a PPI daily as a shield. Many doctors prescribe this long-term for high-risk patients.

There’s also misoprostol, a prostaglandin analog. It helps rebuild the stomach lining. But it’s not popular-it causes cramping and diarrhea. And if you’re a woman of childbearing age? It can cause miscarriage. So it’s rarely used.

The best move? Use the lowest effective NSAID dose for the shortest time. And always pair it with acetaminophen (Tylenol) when you can. It doesn’t hurt your stomach.

Lifestyle: The Silent Healer

Medicines fix the problem. But your habits keep it from coming back.

• Quit smoking. Smokers heal slower. Their ulcers are more likely to bleed. Smoking cuts blood flow to the stomach lining-exactly what you don’t want.
• Limit alcohol. More than three drinks a day triples your risk. Even moderate drinking can irritate an already damaged lining.
• Don’t self-medicate. Over-the-counter painkillers are not harmless. Read labels. Don’t take multiple NSAIDs at once.
• Manage stress. It won’t cause an ulcer, but it can make pain feel worse and slow healing.

What Happens After Treatment?

After finishing your antibiotics and PPI, you’ll need a follow-up test. Not because you feel bad. Because you might still have H. pylori. The breath test or stool test is the gold standard for confirmation. Don’t skip it. Up to 20% of people don’t clear the infection on the first try.

If the ulcer doesn’t heal? That’s called a refractory ulcer. It’s usually because:

• You didn’t take the meds correctly
• The bacteria are resistant
• You’re still taking NSAIDs
• You’re still smoking

In rare cases, it could be something else-like stomach cancer. That’s why endoscopy is often repeated if healing doesn’t happen.

The Big Picture

Peptic ulcer disease used to be a chronic, lifelong condition. Now, it’s a fixable problem. The cure rate for H. pylori is over 85% with proper treatment. The market for ulcer meds is growing-$18 billion by 2028-because people still need pain relief, and we still need better ways to protect the stomach.

The future? Personalized treatment. Before prescribing antibiotics, doctors will test for resistance patterns. One-size-fits-all is fading. And with new drugs like vonoprazan, healing will get faster and more reliable.

But the real win? You don’t have to live with pain. You don’t have to fear bleeding. You don’t have to be afraid of your own stomach. The science is clear. The tools exist. All you need is to get tested-and stick with the plan.