Acid blockers (PPIs): what they change in the gut and how to stop them properly

Healthy state

The parietal cells of the stomach lining pump acid into the stomach with an enzyme, the proton pump. Proton pump inhibitors Proton pump inhibitors (PPIs) Acid blockers such as omeprazole or pantoprazole. They inhibit the acid pump in the stomach lining. , PPIs for short, block this pump. Well-known active ingredients are omeprazole, pantoprazole and esomeprazole. They lower acid more strongly and for longer than older drugs and reliably heal oesophagitis and ulcers.

But stomach acid has several tasks. It kills a large part of swallowed germs, activates the protein-splitting pepsin, releases vitamin B12 from food, helps absorb iron and magnesium and, via the duodenum, gives the start signal for further digestion.

In an empty stomach the pH is around 1 to 2. This acidic environment is a barrier: many bacteria do not survive it, and what comes down from the mouth and throat is largely held back in the stomach. The acid is also a signal. When acidic chyme reaches the duodenum, its lining releases secretin Secretin A hormone from the duodenum. It is triggered by stomach acid and makes the pancreas and bile ducts release bicarbonate to neutralise it. More in the chapter “The digestive chain: how stomach acid, bile and pancreas set each other off”, a hormone that prompts the pancreas to release bicarbonate. The bicarbonate neutralises the acid and so creates the right conditions for the digestive enzymes in the small intestine.

The body notices when acid is missing. It releases more gastrin, the hormone that drives acid production. The parietal cells multiply. As long as the PPI is working, this goes unnoticed.

Guidelines see clear reasons for long-term therapy: severe oesophagitis, Barrett's oesophagus, previous stomach bleeding and a high bleeding risk, for example with blood thinners together with painkillers. For uncomplicated reflux, the US professional society AGA recommends trying to lower the dose or stop after successful short-term treatment.

Because the drugs work so well and are well tolerated, they are often taken for years, even when the original reason is long gone. Professional societies point out that a considerable share of long-term use has no clear ongoing indication, often because the drug was started in hospital or as protection against stomach bleeding and never reviewed again. That is the main reason this chapter exists: not against the PPI, but for a conscious decision.

Disrupted state: causes and effects

In three Dutch cohorts with 1815 people, the gut flora Microbiome, gut microbiota The community of all microbes in the gut, mainly bacteria, plus viruses, fungi and archaea. Most live in the colon. More in the chapter “Building microbial diversity” of PPI users was less diverse, and around a fifth of bacterial groups were changed. There were more bacteria that normally live in the mouth and throat. At population level, the effect was larger than that of antibiotics.

When acid falls as a barrier, the journey of germs changes. Bacteria from the mouth and throat, such as streptococci and Veillonella, survive the stomach more easily and settle in the small and large intestine. At first this is a shift in composition, not automatically a disease. In some people with corresponding risks, such as disturbed small intestinal movement, diverticula Diverticula Small pouches of the gut lining that bulge through weak spots in the colon wall. When they become inflamed, it is called diverticulitis. More in the chapter “Diverticula, haemorrhoids and fissures: what can go wrong at the end of the gut” in the small intestine or a missing ileocaecal valve, it can turn into small intestinal bacterial overgrowth Small intestinal bacterial overgrowth (SIBO) Too many bacteria in the small intestine, where normally few live. Bloating and diarrhoea are typical; it is usually diagnosed with a breath test. More in the chapter “When the small intestine is too densely colonised”. More in the chapter on small intestinal bacterial overgrowth.

The consequences show up in infections. In a large trial, 17,598 people with cardiovascular disease received pantoprazole or placebo Placebo A dummy treatment without an active ingredient. Comparing with it shows how much a remedy achieves beyond expectation and chance. for three years. Gut infections were somewhat more common with pantoprazole, 1.4 versus 1.0 per cent. C. difficile Clostridioides difficile A bacterium that can spread after antibiotics and cause severe diarrhoea with its toxins. More in the chapter “After antibiotics: C. difficile and faecal transplants” occurred about twice as often, but with only 13 cases in total this difference was not statistically significant. Small intestinal bacterial overgrowth is also more common on PPIs.

Infections from food are also caught more easily. Stomach acid intercepts many pathogens that arrive with food and water, for example Salmonella or Campylobacter. Under PPIs fewer germs are enough to cause illness. This explains why travellers on acid blockers may have a slightly higher risk of diarrhoea. They should not stop right away because of this, but should pay attention to food hygiene.

For many other feared consequences, the same trial found no difference: pneumonia, fractures, kidney disease, dementia, cancer and mortality were not increased. The warnings came from observational studies, in which sicker people take PPIs more often. In a large study, more than two years of use was associated with a 65 per cent higher risk of vitamin B12 deficiency. For magnesium the data are inconsistent.

Without acid, nutrient absorption also changes. Iron from plant foods is absorbed less well at higher pH, calcium carbonate tablets dissolve less well (calcium citrate depends less on it), and vitamin B12 is only released from protein-rich food with acid and pepsin. You usually notice this only after years. Those at risk are mainly older people, people on vegetarian or vegan diets, with low iron stores or already existing inflammation of the stomach lining. Some medications need acid to dissolve; with long-term medication this belongs in the discussion too.

One observation that makes you sit up: in 152 adults without known allergy, after three months of acid blockers, 10 per cent had more and 15 per cent had new IgE antibodies IgE The antibody of classic allergy. It sits on mast cells and triggers their alarm on contact with the allergen. More in the chapter “Allergies and intolerances: how the gut learns to tolerate food” against foods such as milk, celery or wheat. Without acid, food proteins are broken down less in the stomach and arrive in the gut as larger pieces. In infants, giving acid blockers was associated with more food allergies. These are associations, not proof.

And stopping has a trap. Because the body has made more gastrin and more parietal cells, acid temporarily overshoots after stopping. In one study, 44 per cent of healthy people without previous symptoms developed heartburn or belching on stopping after eight weeks of PPIs, compared with 15 per cent on placebo. Many take this for a relapse and keep taking the PPI.

Rebound or relapse? Telling them apart helps with stopping. Rebound typically appears in the first days to weeks and then fades as gastrin and parietal cells return to normal. A true relapse persists, tends to get stronger and returns with the old triggers. What you write down during this time helps your doctor decide. Warning signs such as difficulty swallowing, weight loss, black stool or vomiting should always be checked right away.

Finally, a word about people and course. In infants and children, PPIs only make sense with a clear indication; the frequent spitting up of small children is normal and no case for acid blockers. In older people, more medications and an already lower acid production play a role. And if symptoms do not go away on a PPI, acid is not always the cause: some people have an oversensitive oesophagus or functional heartburn, where less acid changes nothing. This should be investigated instead of raising the dose again and again.