Short-Term Antibiotic Use Can Lead to Prolonged Bacterial Resistance in Human Microbiome

Side effects of the antibiotic Cipro (ciprofloxacin) taken for just a five-day course may significantly disrupt some patients’ gut bacteria for up to a year.

While experts have long linked antibiotic overuse to a risk of antibiotic-resistant superbugs, new research suggests that even brief prescriptions can significantly disturb the balance of healthy gut bacteria and lead to serious side effects.

According to findings published in the journal Nature on April 23, using antibiotics like Cipro and Ciloxan for short durations causes disruptions to the gut microbiome for up to 10 weeks after use. 

The human microbiome is a collection of microorganisms that live in the gut, which help with digestion, nutrition, immunity and vitamin production.

Disruptions of the microbiome can lead to digestive problems like gas, bloating, diarrhea and the development of food sensitivities. These side effects are known as dysbiosis, which is an imbalance in the gut microbiome that can lead to increased vulnerability to infections, inflammatory bowel disease, ulcerative colitis, Crohn’s disease and other digestive problems.

In the new study, researchers from Stanford University examined data on 60 healthy adults who were given 500 mg of the antibiotic Cipro for five days. The research team, led by Dr. Eitan Yaffe, collected stool samples across a 20-week period.

The research team then used a new computational method to sequence the genomes of more than 5,600 populations of bacterial species in the participants. Across the study period they analyzed more than 2.3 million polymorphic sequence variants.

The resulting data indicates antibiotic use for even just five days led to persistent antibiotic resistance in human gut bacteria that lasted for more than 10 weeks. The antibiotic resistance emerged independently across different species of bacteria.

Cipro belongs to a class of broad-spectrum antibiotics known as fluoroquinolones, that work by interfering with bacterial DNA replication. According to the findings, 513 populations of bacteria experienced genetic mutations linked to fluoroquinolone resistance. The bacteria showed evidence of adaptive evolution to antibiotic resistance, the researchers warned.

Once the resistance was established, it persisted beyond 10 weeks. In some participants, it was detectable for up to one year. Researchers noted that other antibiotic resistance was found in other genes, but those were less common and appeared in fewer species.

The researchers concluded the findings highlight the need for monitoring microbial composition and abundance of the gut, before and during treatment, to help reduce antibiotic resistance and improve overall stewardship of antibiotic use.

Antibiotic Resistance Concerns

Antimicrobial resistance is a global health concern linked to millions of deaths each year, with the United Nations warning that antibiotic resistant superbugs pose a serious threat to human health.

Researchers have long worried about antibiotic resistant bacteria and the link to global health concerns. Research published in 2024 warned antibiotic resistant bacteria or “superbugs” will kill nearly 40 million people by 2050.

Worse yet, studies indicate the proliferation of antibiotic resistant bacteria is outpacing the development of new antibiotics that can treat resistant bacteria.

Doctor overprescribing and inappropriate prescribing has long been implicated for the emergence of antibiotic resistant bacteria. For example, less than one-third of pediatric antibiotic prescriptions were appropriate for the diagnosis given, according to a recent Vanderbilt University Medical Center study.

The issue of antibiotic overuse is also a major problem in nursing homes. Roughly 20% of nursing homes account for half of all infections of methicillin-resistant staphylococcus aureus (MRSA) bacteria, a type of antibiotic resistant bacteria.