Even non-antibiotics can disrupt the microbiome

The human intestine is home to a dense network of microorganisms, known collectively as the gut microbiome, which shape our health by helping with digestion, training the immune system and protecting against dangerous intruders. It is well known that the use of antibiotics can disrupt this protection, but now it turns out that even non-antibiotic medications can change the microbiome so that pathogens can colonise the gut more easily and cause infections.

A research team led by the University of Tübingen studied 53 common non-antibiotics, including allergy remedies, antidepressants and hormone drugs. Their effects were tested in the laboratory in synthetic and real human gut microbial communities, with the results published in the journal Nature. It turns out that that about one-third of these medications promoted the growth of Salmonella — bacteria that can cause severe diarrhoea.

“The scale of it was utterly unexpected,” said study leader and senior author Professor Lisa Maier. “Many of these non-antibiotics inhibit useful gut bacteria, while pathogenic microbes such as Salmonella Typhimurium are impervious. This gives rise to an imbalance in the microbiome, which gives an advantage to the pathogens.”

The researchers observed a similar effect in mice, where certain medications led to greater growth of Salmonella. The consequence was severe disease progression of a salmonellosis, marked by rapid onset and severe inflammations. This involved many layers of molecular and ecological interactions: medications reduced the total biomass of the gut microbiota, harmed biodiversity or specifically eliminated microbes that normally compete for nutrients with the pathogens. This resulted in a change in the microbiome creating a more favourable environment for pathogenic microbes such as Salmonella, which were then able to proliferate unimpeded.

“Our results show that when taking medications, we need to observe not only the desired therapeutic effect but also the influence on the microbiome,” said co-lead author Anne Grießhammer. “While the necessity of drugs is unnegotiable, even drugs with supposedly few side effects can, so to speak, cause the microbial firewall in the intestine to collapse.”

“It’s already known that antibiotics can damage the gut microbiota,” Maier added. “Now we have strong signs that many other medications can also harm this natural protective barrier unseen. This can be dangerous to frail or elderly people.”

Maier’s team has now developed a high-throughput technology which allows testing of how medications influence the resilience of the microbiome under standard conditions. They also recommend that in the future, medications should be assessed not only pharmacologically but also microbiologically — especially for drug classes such as antihistamines, antipsychotics or selective oestrogen-receptor modulators as well as for combinations of several medications.

“If you disrupt the microbiome, you open the door to pathogens — it is an integral component of our health and must be considered as such in medicine,” Maier concluded.

Image caption: Scanning electron microscopy image of a gut bacterial community. Medications can eliminate beneficial bacteria and thereby promote the growth of harmful species. Image produced by the Maier Lab (Lisa Maier, Anne Grießhammer, Leonardo Boldt) together with the Tübingen Structural Microscopy Core Facility (Michaela Wilsch-Bräuninger, Stefan Fischer). Colouring: Elke Neudert.