The human intestine hosts a complex ecosystem of microorganisms known as the gut microbiome, which plays a crucial role in maintaining our health. These microorganisms aid digestion, train the immune system, and defend against harmful invaders. However, this protective function can be disrupted, not only by antibiotics designed to target pathogenic bacteria but also by various other medications.
A recent study reveals that many common drugs aimed at different bodily systems can alter the microbiome, making it easier for pathogens to colonize the gut and cause infections. The research, led by Professor Lisa Maier from the Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT) and the Cluster of Excellence Controlling Microbes to Fight Infections (CMFI) at the University of Tübingen, has been published in Nature.
NatureThe researchers examined 53 common non-antibiotic drugs, including allergy treatments, antidepressants, and hormone therapies. They tested these medications' effects on both synthetic and real human gut microbial communities in a laboratory setting. They discovered that approximately one-third of these medications promoted the growth of Salmonella bacteria, known for causing severe diarrhea.
Professor Maier, senior author of the study, remarks, "The scope of this effect was completely unexpected. Many non-antibiotic drugs inhibit beneficial gut bacteria while pathogenic microbes like Salmonella Typhimurium remain unaffected. This imbalances the microbiome and gives pathogens a competitive advantage."
The researchers observed similar effects in mice, where certain medications led to increased growth of Salmonella, resulting in severe salmonella infection with rapid onset and intense inflammation.
Anne Grießhammer and Jacobo de la Cuesta, lead authors of the study from Maier's research group, explain that these drugs disrupt multiple layers of molecular and ecological interactions. Medications reduced the overall mass of gut microbiota, harmed biodiversity, or specifically eliminated microbes competing with pathogens for nutrients. This altered the microbiome, creating a favorable environment for pathogenic microbes like Salmonella to proliferate uncontrolled.
"Our findings underscore the need to consider both the therapeutic benefits and the effects on the microbiome when taking medications," says Grießhammer. "Even drugs thought to have minimal side effects can compromise the gut's microbial defense mechanism."
Professor Maier adds, "It is well-known that antibiotics can damage the gut microbiota; now we have evidence that many other medications may also harm this natural protective barrier, potentially endangering vulnerable or elderly individuals."
The researchers advocate for systematic evaluation of drugs' effects on the microbiome during development, especially for classes like antihistamines, antipsychotics, and selective estrogen-receptor modulators, as well as combinations of multiple medications.
Maier's team has developed a new high-throughput technology that allows rapid, reliable testing of how medications influence the resilience of the microbiome under standard conditions. These findings suggest that pharmaceutical research needs to reconsider its approach: future drug assessments should evaluate not only pharmacological effects but also microbiological impacts.
"Disrupting the microbiome can open the door to pathogens—it is a crucial component of our health and must be recognized as such in medical practice," Maier emphasizes.
Professor Dr. Dr. h.c. (Dôshisha) Karla Pollmann notes, "The microbiome research at Tübingen has made an important discovery. Incorporating the effects on the microbiome into drug development could lead to more suitable treatments with reduced side effects for patients in the long term."