Intestinal problems caused by non-antibiotics are more common than previously thought

How "normal" medications pave the way for pathogens

Unexpectedly common side effect: Not only antibiotics, but also a surprisingly large number of other classes of active ingredients weaken our intestinal flora and thus the natural protective function of the intestine. As a result, pathogenic bacteria such as salmonella can more easily colonize there, as researchers report in "Nature." These side effects of common medications have so far been overlooked, but should be taken into account when developing new active ingredients.

Medications from more classes of active ingredients than previously thought disrupt our intestinal flora.

Our intestines are home to trillions of beneficial microorganisms that actively influence our health. The bacteria in our intestinal flora, for example, help with digestion, train our immune system, and protect us from invaders. However, the intestinal microbiome can only inadequately perform these tasks if some of its members are killed and the community becomes unbalanced. This can occur as a side effect of antibiotics, which, in addition to pathogenic bacteria, also inadvertently kill health-promoting intestinal inhabitants.

Side effects of non-antibiotics investigated

But how do other medications affect the intestinal flora – those that are not antibiotics and therefore do not primarily target bacteria, but rather other targets in our body? Initial studies suggest that they can also have negative side effects. A team led by Anne Grießhammer from the University of Tübingen has now examined this in more detail using over 1,000 medications.

The microbiologists are testing 53 common non-antibiotics, including allergy medications such as antihistamines, antidepressants, and hormone preparations. They analyzed the effects of these drug classes on the intestinal flora using human intestinal communities cultured in the laboratory, consisting of dozens of bacteria. They also tested the effect in mice.

Drugs Facilitate the Spread of Salmonella and Other Bacteria

The analysis showed that around one-third (28 percent) of the tested active ingredients disrupted the balance of the intestinal flora and promoted the growth of Salmonella. These bacteria can cause severe diarrhea. In mice, these drugs even led to severe salmonellosis, characterized by a rapid onset of disease and severe inflammation. "This extent was completely unexpected," says senior author Lisa Maier from the University of Tübingen.

Through their interactions, microorganisms form an ecosystem essential to human health. Drugs can disrupt this fragile balance. © Lisa Maier/ Maier Lab

But how does this happen? The drugs act in different ways, which can occur individually or simultaneously, as the researchers discovered: Some reduce the overall biomass of the intestinal flora, others disrupt biodiversity and composition, or eliminate bacteria that compete with pathogens for nutrients. Without natural competitors, pathogenic bacteria like Salmonella can then multiply unhindered.

"Many of these non-antibiotic drugs inhibit beneficial intestinal bacteria, while pathogenic bacteria like Salmonella Typhimurium are resistant. This creates an imbalance in the microbiome that gives pathogens the advantage," explains Maier.

Antibiotics aren't the only thing that endangers the intestinal flora.

According to this study, non-antibiotic medications can also alter the microbiome in our intestines, making it easier for pathogens to grow and cause infections. "It is known that antibiotics can disrupt the intestinal flora. Now we have strong evidence that many other medications also inadvertently damage this natural protective barrier," says Maier.

"Our results show that when taking medications, not only the desired therapeutic effect must be observed, but also the impact on the microbiome," adds Grießhammer. "Even active ingredients with seemingly few side effects can cause the intestinal microbial barrier to collapse." This could be dangerous for weakened or elderly people.

New screening tool for drug development

To ensure that new medications cause such unintended side effects in the intestines less frequently in the future, their effects on the intestinal flora should be more systematically investigated during drug development, the researchers recommend. The effects of combining several medications on the intestinal flora should also be considered and researched. To enable rapid and reliable testing, Grießhammer and her colleagues have already developed a new high-throughput method that allows for the simultaneous screening of many combinations of microbes and active ingredients at different doses.

The exact molecular and cellular processes by which the drugs affect the intestinal flora are still unclear. These will be investigated in more detail in follow-up studies. It is also still unknown whether and how quickly the intestinal microbiome self-regulates after discontinuation of drug use.

(Nature, 2025; doi: 10.1038/s41586-025-09217-2)

Source: Eberhard Karls University of Tübingen