In a battle against an infection, antibiotics can bring victory over enemy germs. Yet that war-winning aid can come with significant collateral damage; microbial allies and innocents are killed off, too. Such casualties may be unavoidable in some cases, but a lot of people take antibiotics when they’re not necessary or appropriate. And the toll of antibiotics on a healthy microbiome can, in some places, be serious, a new study suggests.

In two randomized, placebo-controlled trials of healthy people, a single course of oral antibiotics altered the composition and diversity of the gut microbiome for months, and in some cases up to a year. Such shifts could clear the way for pathogens, including the deadly Clostridium difficile. Those community changes can also alter microbiome activities, including interacting with the immune system and helping with digestion. Overall, the data, published Tuesday in the journal mBio, suggests that antibiotics may have more side effects than previously thought—at least in the gut.

In the mouth, on the other hand, researchers found that microbial communities fared much better, rebounding in weeks after antibiotic treatments. The finding raises the question of why the oral microbiome is less disturbed by drugs. It could simply be because of the way that antibiotics, taken orally, circulate through the body. Or, it could imply that oral microbiomes are innately more resilient, a quality that would be useful to replicate in microbial communities all over the body.

The joint trials, led by Egija Zaura at the University of Amsterdam, followed 66 healthy participants, 29 in Sweden and 37 in the United Kingdom. At each location, participants were randomly assorted into either a placebo group or one of two groups given antibiotics. The two antibiotics given in the Swedish trial were a lincosamide (clindamycin) and a quinolone (ciprofloxacin). The UK trial included a tetracycline (minocycline) and a penicillin (amoxicillin).

Researchers sequenced microbes of each person’s saliva and feces before and immediately after they took a course of drugs. Then the researchers did follow up sampling at 1, 2, 4, and 12 months.

Gut microbial diversity was significantly altered by all four kinds of antibiotics, which lasted for months. In participants that took ciprofloxacin, microbial diversity was altered for up to 12 months. The antibiotic treatments also caused a spike in genes associated with antibiotic resistance. Lastly, the researchers noted that clindamycin killed off microbes that produce butyrate, a short-chain fatty acid that inhibit inflammation, carcinogenesis, and oxidative stress in the gut.

The oral microbiome saw some community shifts. But the communities surprisingly rebounded within a short time—in some cases a week—the authors report. And, the amount of genes associated with antibiotic resistance were generally stable before and after drug treatments.

The authors speculate that the oral microbiome’s steadiness may be related to the constant onslaught of disturbances, such as tooth brushing and changes in moisture and air.

mBio, 2015. DOI: 10.1128/mBio.01693-15 (About DOIs).