Antibiotic Use Linked to Long-Term Gut Microbiome Alterations in Large Cohort Study

Research published in Nature Medicine on April 14, 2026, indicates that oral antibiotic use can lead to long-term alterations in the gut microbiome, with some effects persisting for four to eight years after treatment.

The study, led by scientists at Uppsala University, examined 14,979 adults by integrating fecal metagenomes with data from the Swedish National Prescribed Drug Register. The findings suggest that the gut microbiome may act as a fingerprint of an individual’s antibiotic use history.

Impact and Duration of Microbiome Changes

Researchers found that antibiotic use within one year prior to fecal sampling was associated with the most significant reduction in species diversity. However, significant associations remained evident for antibiotic use occurring one to four years and four to eight years before the samples were taken.

The data revealed that these long-lasting traces can occur even after a single course of treatment. The extent of the impact varied significantly depending on the class of antibiotic administered.

Specific antibiotics were more strongly associated with changes in the abundance of individual species than others:

• Clindamycin, fluoroquinolones and flucloxacillin accounted for the majority of associations with individual species abundance.
• Use of these specific antibiotics four to eight years prior was associated with altered abundance in 10% to 15% of the studied species.
• Penicillin V, nitrofurantoin, and extended-spectrum penicillins were associated with changes in only a few species.

Clinical Context and Health Implications

While antibiotics are essential for treating serious infections, disruptions to the gut microbiome are implicated in various health outcomes. Observational studies have linked recurrent and long-term antibiotic use to an increased risk of several conditions, including:

• Type 2 diabetes
• Obesity and overweight
• Cardiovascular disease
• Colorectal polyps and cancer

The researchers noted that while the short-term impact of antibiotics on the gut microbiome is well documented, the duration of these changes has previously been unclear. This study provides evidence that the footprint of these drugs can be persistent.

One 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,

Gabriel Baldanzi, first author of the study and former doctoral student at Uppsala University

The study was conducted in Sweden, a country that Gabriel Baldanzi noted already maintains a strict antibiotic stewardship.

Research Methodology and Findings

The team utilized multivariable confounder-adjusted regression models to analyze the relationship between drug records and metagenomic profiles. The results remained consistent when comparing individuals who had one antibiotic course four to eight years before sampling against those who had used no antibiotics in the past eight years.

This research adds to previous findings, such as an intervention study showing that broad-spectrum antibiotics produce microbiome alterations persisting for at least 180 days. However, the Uppsala University study extends this timeline significantly, showing potential effects lasting nearly a decade.