Antibiotics can be lifesaving treatments for serious infections, but new research suggests their effects on the gut microbiome may last much longer than previously thought.

In a large study published March 11 in Nature Medicine, researchers found that antibiotic use was linked to measurable changes in gut bacteria as long as four to eight years after treatment. The findings come from an analysis of nearly 15,000 adults in Sweden whose prescription histories were linked to detailed microbiome data.

The research was led by scientists at Uppsala University and explored how a person’s past antibiotic use relates to the diversity and composition of bacteria living in the digestive system.

“We can see that antibiotic use as far back as four to eight years ago is linked to the composition of a person’s gut microbiome today. Even a single course of treatment with certain types of antibiotics leaves traces,” said Gabriel Baldanzi, the study’s first author and a former doctoral student at Uppsala University.

Antibiotics work by killing or inhibiting bacteria that cause infections. But they can also affect beneficial microbes that live in the human body, particularly in the gut. Scientists have long known that antibiotics can disrupt the microbiome in the short term. What has been less clear is how long those changes persist.

To investigate, the researchers analyzed prescription drug registry data alongside microbiome samples collected from 14,979 participants in Swedish population studies. The team compared the gut microbiomes of people who had received antibiotics in the past with those who had not taken antibiotics during the study period.

The analysis revealed that antibiotic history was strongly linked to the composition and diversity of gut bacteria, even years after treatment.

The effects varied depending on the type of antibiotic used. The strongest associations were seen with clindamycin, fluoroquinolones and flucloxacillin. By contrast, penicillin V, a commonly prescribed antibiotic for infections treated outside hospitals in Sweden, was associated with smaller and shorter-lived changes to the microbiome.

“The strong link between the narrow-spectrum flucloxacillin and the gut microbiome was unexpected, and we would like to see this finding confirmed in other studies,” said Tove Fall, professor of molecular epidemiology at Uppsala University and the study’s principal investigator.

Fall noted that the findings could eventually help inform decisions when doctors choose between different antibiotics that are equally effective for treating an infection.

“However, we believe that the findings of our study may help inform future recommendations on antibiotic use, especially when choosing between two equally effective antibiotics, one of which has a weaker impact on the gut microbiome,” Fall said.

The researchers emphasize that antibiotics remain essential treatments and should be used when prescribed by medical professionals. Sweden already has strict antibiotic stewardship policies designed to reduce unnecessary use while ensuring patients receive appropriate care.

The study also has several limitations. The researchers analyzed prescription data from the previous eight years, so longer-term effects beyond that period remain unclear. In addition, each participant’s gut microbiome was sampled only once.

Scientists are now collecting additional microbiome samples from many of the same participants. Those follow-up data may help researchers better understand how long the microbiome takes to recover after antibiotic exposure and why some individuals appear more vulnerable to lasting disruptions than others.

As research into the microbiome continues, scientists are increasingly interested in how medications, diet and lifestyle factors shape the complex ecosystem of bacteria that live in the human gut.

The study was conducted by researchers at Uppsala University using Swedish national prescription records and microbiome data from population cohorts. The research was published in the peer-reviewed journal Nature Medicine.

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