Antibiotic Prescriptions Linked to Gut Microbiome Alterations Years Later, with Gabriel Baldanzi, MD, MSc

A landmark study published in Nature Medicine reveals the "footprint" of a single antibiotic course on the human gut microbiome can persist for up to 8 years. Analyzing individual-level prescription data from 14,979 Swedish adults, investigators found specific antibiotic classes significantly reduce microbial diversity and alter species abundance long after the initial treatment.¹

“We can see that antibiotic use as far back as 4 to 8 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,” stated Gabriel Baldanzi, MD, MSc the first author of the study and a former doctoral student at Uppsala University.

While it is well-established antibiotics cause acute disruptions to the gut flora, this study provides unprecedented evidence of long-term consequences. Investigators linked fecal metagenomes to the Swedish Prescribed Drug Register, tracking antibiotic use over an 8-year period. Fecal metagenomics data that were collected as part of 3 population-based cohorts in Sweden: Swedish CArdioPulmonary bioImage Study (SCAPIS, n = 8488), Swedish Infrastructure for Medical Population-based Life-course and Environmental

Research (SIMPLER, n = 4784) and the Malmö Offspring Study (MOS, n = 1707). They discovered antibiotic use 4 to 8 years prior to sampling was still associated with reduced alpha diversity and altered abundance in approximately 10% to 15% of studied species.^1,2

The study identified 3 classes with the most profound long-term effects: clindamycin, fluoroquinolones, and flucloxacillin. For example, a single course of clindamycin taken less than a year before sampling was associated with an average loss of 47 microbial species. Notably, flucloxacillin—a narrow-spectrum penicillin—showed a surprisingly large impact, primarily affecting the Bacillota A phylum.

Conversely, penicillin V, extended-spectrum penicillin, and nitrofurantoin were associated with minimal long-term changes. These findings suggest the clinical choice of antibiotic may have lasting implications for a patient's internal ecosystem.

For primary care physicians, these findings add a new dimension to antimicrobial stewardship. Beyond the immediate concern of antibiotic resistance, clinicians must consider the potential for chronic microbiome disruption. The study linked antibiotic-associated species—such as Sellimonas intestinalis and Ruminococcus B gnavus—to higher BMI, serum triglycerides, and C-reactive protein levels. These alterations may contribute to the long-term risk of type 2 diabetes, cardiovascular disease, and inflammatory bowel disease.

Principal investigator Tove Fall, PhD, emphasized when choosing between 2 equally effective treatments, clinicians should prioritize the option with the lower projected impact on the gut microbiome. As the field of metagenomics advances, such "microbiome-sparing" strategies may become central to outpatient infectious disease management.

Patient Care Online sat down with investigator Baldanzi to learn more about how antibiotics can affect gut microbiome for several years.

Patient Care Online: Your research indicates antibiotics can leave a "footprint" on the gut microbiome for 4 to 8 years; can you explain the significance of this duration?

Gabriel Baldanzi: Previous intervention studies have followed individuals for up to 18 months after antibiotic treatment and found evidence of this “footprint.” Other observational studies like ours have examined associations between the number of antibiotic prescriptions in the past 10 years and the gut microbiome (https://doi.org/10.1038/s41467-022-28464-9). However, these studies did not distinguish between recent and past antibiotic use or between different antibiotic classes.

Additionally, these studies did not consider confounders in their analyses. Confounders are differences between antibiotic users and non-users are also linked to the gut microbiome. For example, individuals with type 2 diabetes are more likely to need antibiotics and they also have a different gut microbiome composition from people without diabetes.

In summary, our study shows antibiotic use 4–8 years earlier is associated with gut microbiome composition, even after accounting for more recent antibiotic use and potential confounders. This had never been done before and it represent the strongest evident to date that changes in the gut microbiome produced by antibiotics can last for so long.

Patient Care Online: The study utilized the Swedish Prescribed Drug Register alongside fecal metagenomes from nearly 15,000 adults. How did this specific data infrastructure allow for insights that smaller, short-term studies might miss?

Gabriel Baldanzi: Smaller, short-term studies provide very good evidence for alterations in the gut microbiome observed during the follow-up period. However, it becomes impractical and expensive to follow individuals for a several years. Additionally, the microbiome is highly variable between individuals, so smaller studies may not be able to differentiate between the effects of antibiotics and the natural biological variation in the gut microbiome.

The Swedish Prescribed Drug Register, which captures all antibiotics dispensed to outpatients since 2005, allowed us to examine associations even for antibiotic treatments prescribed up to 8 years earlier. In addition, the large sample size allowed us to link alterations in low-prevalence and/or low-abundance bacteria to antibiotic use. Such alterations would likely not have been detected in studies with smaller sample sizes.

Patient Care Online: Why did clindamycin, fluoroquinolones, and flucloxacillin show such a markedly stronger association with microbiome changes compared to others?

Gabriel Baldanzi: Antibiotics may have a large impact on the gut microbiome for 2 main reasons. The first is the spectrum of activity—in other words, which bacteria are likely to be killed by the antibiotic. Fluoroquinolones are known to kill many types of bacteria, including Gram-positive and Gram-negative bacteria.

The second reason is how the antibiotic is removed from the body. Some antibiotics, including clindamycin, undergo so-called enterohepatic circulation. This means that they are absorbed in the intestine into the bloodstream but are then secreted back into the intestines by the liver. These antibiotics can therefore reach very high concentrations in the intestine, including the last part (the colon), where most of the gut microbiome is located.

The strong association between flucloxacillin use and gut microbiome composition was a surprise, as this antibiotic is considered to have a narrow spectrum of activity against Gram-positive bacteria. Therefore, our findings may be related to enterohepatic circulation of flucloxacillin. However, as far as we know, the intestinal levels of flucloxacillin in the gut have not yet been well characterized.

Patient Care Online: The study suggests even a single course of treatment can leave traces years later. How should this finding influence the "risk-benefit" conversation during a standard patient consultation?

Gabriel Baldanzi: Antibiotics are important medications that save lives. At the same time, the emergence of antimicrobial resistance is the major threat to the efficacy of antibiotic treatment. Although the effects of antibiotics on the gut microbiome are undesirable, antimicrobial resistance should remain the main reason for restricting antibiotic use.

Patient Care Online: Epidemiological studies have linked high antibiotic use to an increased risk of type 2 diabetes and gastrointestinal infections. Based on your findings, what role does the microbiome's "long-term footprint" play in the pathogenesis of these conditions?

Gabriel Baldanzi: This is definitely an area that requires more research. We observed that the use of certain antibiotics was linked to a higher abundance of bacteria that are also found at higher abundance in individuals with type 2 diabetes. However, this is not the final evidence that changes in the gut microbiome caused by antibiotics are contributing to the pathogenesis of type 2 diabetes. Our results can inform future research about gut microbiome alterations are more likely to be involved.

Regarding viral and common bacterial gastrointestinal infections, more work needs to be done. In the case of gastrointestinal infections caused by the bacterium Clostridium difficile, the link between antibiotic use and this infection is well established, and acute changes in the gut microbiome are considered the main driver.

Patient Care Online: The current data relies on a single fecal sample per participant. What are the inherent limitations of this "snapshot" approach when studying a dynamic system like the microbiome?

Gabriel Baldanzi: Great question. There may be antibiotic-induced alterations that we were unable to detect using only 1 sample per participant, especially those involving bacterial species that are absent in most individuals or species that vary greatly in abundance between individuals. We have a high degree of confidence that the alterations we detected actually exist, but having repeated samples from the same individuals would help us obtain more precise estimates of the magnitude of the changes and the rate of recovery.

Note: The above transcript has been lightly edited for grammar and clarity.

References:

1. Antibiotics can affect the gut microbiome for several years. EurekAlert! Published March 11, 2026. Accessed March 16, 2026. https://www.eurekalert.org/news-releases/1119005?
2. Baldanzi G, Larsson A, Sayols-Baixeras S, et al. Antibiotic use and gut microbiome composition links from individual-level prescription data of 14,979 individuals. Nature Medicine. Published online March 11, 2026:1-11. doi:https://doi.org/10.1038/s41591-026-04284-y