New Research Disputes That Antibiotics Can Cause MC

by Wayne Persky

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For years, antibiotics have been suspected of contributing to the development of microscopic colitis (MC). However, a major new study suggests this link may be overstated, and possibly a result of diagnostic bias, rather than a true biological effect.​

Researchers from the Karolinska Institutet in Sweden conducted a nationwide, self-controlled case series study examining 2,393 individuals aged 65 and older who were prescribed antibiotics and later diagnosed with biopsy-confirmed MC between 2007 and 2017.

The study was published in Alimentary Pharmacology & Therapeutics and also summarized by an online Medscape article under the headline “Antibiotics Getting False Blame for Colitis” (Szilcz. Wastesson, Bergman, Johnell, and Ludvigsson, 2025; Rai, 2025, February 21).”1, 2 The study found that:

The risk was slightly increased during and after antibiotic treatment:

​

• During antibiotic treatment there was a 44% increased risk of a diagnosis of MC (adjusted incidence rate ratio [aIRR] = 1.44)
• In the 3–12 months following-treatment, there was a 19% increased risk (aIRR = 1.19)
• The short-term risk (during the first 3 months after treatment) was modest or statistically insignificant

But negative controls show a similar pattern.

• A parallel analysis of over 19,000 patients who underwent colon biopsy but were found to have normal mucosa showed a similar increase in diagnoses following antibiotic use.
• This suggests diagnostic workups (triggered by GI symptoms from antibiotic use) may explain the apparent association with MC, rather than a direct causative effect.​

In other words, antibiotics are notorious for causing diarrhea, and this might present the illusion of causing MC.

The study found that:

• Women and individuals aged 80 and older had slightly higher risk increases.
  
• The two most commonly prescribed antibiotics were penicillin V (50%) and doxycycline (35%).
  

So why are antibiotics thought to cause MC?

Antibiotics are frequently implicated because they commonly cause chronic, watery, nonbloody diarrhea, suggestive of MC. And because of this characteristic, subsequent investigation frequently uncovers pre-existing, asymptomatic cases of MC.

When a colonoscopy is used to evaluate chronic, watery, nonbloody diarrhea:

• 10 to 15% result in a diagnosis of MC.
• 30 to 50% have no visible or microscopic inflammation. This is often diagnosed as "functional diarrhea" or irritable bowel syndrome with diarrhea (IBS-D).
• 5 to 10% are found to be due to other microscopic abnormalities, including nonspecific colitis, drug-induced changes, or early IBD.
• 5 to 10% are found to have macroscopic inflammation, including Crohn's disease or ulcerative colitis (UC), with mucosal changes visible during the colonoscopy.
• 5 to 10% result in other diagnoses, including ischemic colitis, bile acid diarrhea, radiation colitis, or eosinophilic colitis.
• 10 to 15% result in nonspecific findings, or mild histologic changes, which may show subtle lymphocytic infiltration, mild edema, or inflammation without clear diagnostic criteria.
• 1 to 5% are found to have "infectious colitis" (this is often diagnosed by's stool tests, not colonoscopy)
• 1 to 2% may be attributed to colorectal cancer or polyps, although this is a somewhat rare cause of watery diarrhea, unless the tumor is large or secretory.

So based on the statistics, if antibiotics trigger chronic, watery, nonbloody diarrhea, it's not surprising that gastroenterologists might expect to find MC. But obviously a large portion of people with chronic diarrhea (30 to 50%) will have a completely normal colonoscopy, with normal, or near-normal biopsies, resulting in a diagnosis of IBS-D, functional diarrhea, medication -induced diarrhea (for example, metformin, SSRIs, PPIs, magnesium) or bile acid diarrhea (underdiagnosed unless specifically tested).

Note that this research didn't totally exonerate antibiotics.

While it was shown that antibiotics do not cause MC, the study also found that antibiotic associated GI symptoms may lead to additional colonoscopies, thereby increasing the chance of detecting pre-existing MC.

Did the study prove that antibiotics cannot trigger symptomatic flares in previously asymptomatic MC? Well, no, because it didn't test that directly. What it did show was that the rise in MC diagnoses after antibiotic use was matched by a rise in normal colon biopsies, which implies that the antibiotics themselves may not be causing new disease, but rather unmasking existing conditions, by provoking the symptoms of diarrhea.

In other words, the study suggests that antibiotics might provoke symptoms in someone who has asymptomatic or subclinical MC, which then leads to investigation, and a diagnosis of MC. But there's no clear evidence that antibiotics cause MC where it did not exist previously, and no clear evidence that antibiotics convert asymptomatic MC into active disease (this was not specifically investigated).

Medications such as NSAIDs, SSRIs, and PPIs have also long been considered to be possible causes for the development of MC. In view of the findings of this large, well-controlled study that determined the long-held assumption that antibiotics are a significant cause of MC to be without merit, will research soon show that medications such as NSAIDs, SSRIs and PPIs do not cause MC, either?

Probably not, because unlike antibiotics (which don't generally cause chronic inflammation) NSAIDs, SSRIs, and PPIs can definitely cause chronic inflammation, and chronic inflammation commonly causes the development of MC.

References

1. Szilcz, M. Wastesson, J. W., Bergman, D., Johnell, K. and Ludvigsson, J. F. (2025). Antibiotic Use and Risk of Microscopic Colitis in Older Adults: A Nationwide Self-Controlled Case Series Study. Alimentary Pharmacology and Therapeutics, Retrieved from https://onlinelibrary.wiley.com/doi/10.1111/apt.70028

2. Rai, A. (2025, February 21). Antibiotics Getting False Blame for Colitis, Study Finds. Medscape, Retrieved from https://www.medscape.com/viewarticle/antibiotics-getting-false-blame-colitis-study-finds-2025a10004j5?ecd=mkm_ret_250418_mscpmrk_idhiv_antibiotic_etid7362030&uac=95382HN&impID=7362030