Can Long-Term PPI Use Cause SIBO? What Stomach Acid Does for Your Small Intestine
What stomach acid does to protect your small intestine, and what changes when a PPI turns it down.
Photo: Atilla Taskiran / Unsplash
Can long-term PPI use cause SIBO? Long-term use of a proton pump inhibitor (PPI) is associated with a higher rate of SIBO. PPIs are the class of acid-reducing drugs that includes omeprazole and pantoprazole, and SIBO (small intestinal bacterial overgrowth) means too many bacteria are living in the small intestine. Researchers haven't shown that the PPI is the whole cause, and studies disagree about how much the testing method changes the answer. If you have taken a PPI for years and now have SIBO, the medication is a reasonable thing to raise with whoever prescribes it. That is a different step from stopping it on your own.
What stomach acid does for your small intestine
Your stomach makes acid for more than digesting food. Gastric acid is your first line of defense against the bacteria you swallow by accident, and part of its job is to sanitize your food before it moves on. A PPI lowers the amount of acid the stomach lining makes, which is why it helps with reflux. It is also why more of the bacteria that arrive with a meal can survive the trip into the small intestine.
Stomach acid is one protection among several. Between meals, the small intestine clears itself with a wave of muscle activity called the migrating motor complex. When that clearing wave slows down, SIBO tends to come back. I think of a PPI as removing one layer of protection. It raises the odds of SIBO without making it certain, and someone whose motility is also slow has fewer layers left. Weaker stomach acid can make food poisoning more likely too, and food poisoning is one recognized route into post-infectious IBS and SIBO.
What the studies found in people taking PPIs
In 2010, Lombardo and colleagues in Italy gave a glucose breath test to 450 consecutive patients. That group included 200 people with reflux who had taken a PPI for a median of 36 months (three years), 200 people with IBS (irritable bowel syndrome) who had not taken one for at least three years, and 50 healthy control subjects who had not taken a PPI for at least 10 years. SIBO turned up in 50% of the PPI users. That compares with 24.5% of the IBS group and 6% of the healthy controls. The authors also reported that SIBO became more common after the first year of PPI treatment.
With only one study, there's no way to know how typical its result is, which is why researchers pool studies into reviews. In 2025, Khurmatullina and colleagues combined 29 studies covering 3,682 PPI users and 2,907 people not taking one. Across those studies, 36.8% of PPI users had SIBO. In the comparison group it was 19.9%. The odds of SIBO were roughly twice as high in PPI users. When the authors grouped studies by how long people had taken the medication, use beyond six months carried the highest odds, about four times those of nonusers. The one-to-six-month group was close behind, though the estimate for the longest group was imprecise, and the increase could plausibly be anywhere from modest to more than tenfold.
Among the limitations the authors listed was that SIBO has no standardized diagnostic criteria, so the studies used different breath test thresholds and different culture techniques. They also rated 20 of the 29 studies as having moderate methodological limitations. The review included observational studies, meaning ones that compare people who already take a PPI with people who don't. With a design like that, researchers can measure an association, but they can't prove the PPI caused the SIBO.
Why the test you took changes the answer
Some studies have found no link at all. In 2012, Ratuapli and colleagues at Mayo Clinic in Arizona reviewed the charts of 1,191 people who had a glucose breath test. Of those, 566 (48%) were taking a PPI. Positive results didn't differ significantly between PPI users and nonusers under any of the four definitions of a positive test that the researchers applied. Shah's 2020 review, covered below, also found no link between PPI use and SIBO among the people with IBS it included.
A 2013 review by Lo and Chan offers one explanation for disagreements like this. They pooled 11 studies with 3,134 people and found the link between PPIs and SIBO in studies that diagnosed SIBO with aspirate culture. In an aspirate culture, fluid is collected from the small intestine during an endoscopy, and the lab grows whatever bacteria are in it. In studies that used the glucose breath test, the link didn't reach significance. Their conclusion was that PPI use was associated with SIBO only when the diagnosis came from that more accurate test. They added that differences between studies could come from the tests themselves.
The 2025 review reached a different result on that point. In their discussion, the authors reported that the size of the PPI link didn't vary significantly by test, unlike the earlier reviews. Among PPI users, SIBO rates ranged from about a third to two in five across the three main tests. So there is still disagreement over how much the testing method explains.
The sugar used in a breath test changes the count as well. Shah and colleagues published a 2020 review of SIBO in IBS. Lactulose breath tests diagnosed SIBO 3.6 times as often as glucose breath tests in people with IBS, and 7.6 times as often in the comparison groups without IBS. The cutoff your lab uses changes the result too. It helps to know which sugar and which threshold your result was based on.
Questions to bring to whoever prescribes your PPI
PPIs have legitimate uses, and some people need them for a long time. There's an appropriate use for these medications, and healing an ulcer is one example. What I suggest is a regular check-in, roughly every six months, with whoever prescribes the PPI, to ask if you still need it. Any change belongs in that conversation. Stopping suddenly can bring on rebound reflux, which is one more reason to plan it with your prescriber.
Some things to have ready for that conversation:
- Why the PPI was first prescribed, and if that reason still applies
- How long you have been taking it, and at what dose
- Your SIBO result, including which sugar the breath test used and what counted as positive
- How your SIBO plan handles motility once treatment is finished
Other posts on SIBO testing, treatment, and motility are listed on the SIBO hub.
If you want a structured walk-through of SIBO treatment, the SIBO Treatment Algorithm lays out the treatment options, what to do when symptoms don't improve or come back, gentler routes for people who are more sensitive, and the gut and motility repair that comes after.
FAQ
Do PPIs cause SIBO?
Long-term PPI use is associated with SIBO. In a 2025 review of 29 studies, about 37% of PPI users had SIBO compared with about 20% of people not taking one. The review included observational studies, which compare people already taking a PPI with people who aren't, and a design like that can show an association without proving the medication was the cause. Stomach acid helps kill bacteria you swallow, which gives a plausible route, and slowed motility is involved as well.
How long does someone need to take a PPI before SIBO becomes more likely?
There isn't a single cutoff. In a 2010 Italian study, SIBO became more common after the first year of PPI treatment. In a 2025 review, people who had taken a PPI for more than six months had the highest odds, about four times those of nonusers, though that estimate came with a wide margin of uncertainty.
Should I stop my PPI if I have SIBO?
That decision belongs with whoever prescribes the PPI. Some people need acid suppression for a reason such as an ulcer that has to heal, and stopping suddenly can cause rebound reflux. What you can do is ask for a review of your continued need for the PPI, and of the dose.
Can SIBO be treated while someone is still taking a PPI?
In the 2010 Italian study, high-dose rifaximin, a prescription antibiotic, cleared SIBO in 87% of the PPI users while they continued their PPI. That result comes from a single study.
Does the type of breath test change the result?
Yes. In a 2020 review, lactulose breath tests diagnosed SIBO 3.6 times as often as glucose breath tests in people with IBS, and 7.6 times as often in the comparison groups without IBS. A 2013 review found the PPI link in studies that used intestinal fluid cultures, while in studies using glucose breath tests the link didn't reach significance. Knowing which sugar and which cutoff your test used makes the result easier to interpret.
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