In a new study, Cedars-Sinai researchers have found that antibiotics have sex-specific effects on the gut microbiome composition of male and female lab rats. The results, published in the journal Frontiers in microbiologycould have implications for the use of drugs in humans to treat or prevent bacterial infection.
We found that giving rats a multi-drug antibiotic cocktail caused significant, sex-specific changes in both the feces, or large intestine, and the small intestine. For example, a greater loss of microbe diversity in the feces and small intestine was observed in male rodents than in females.”
Ruchi Mathur, MD, study principal investigator
“Changes in the diversity of the gut microbiome could have a negative impact. Previous studies on gut health have demonstrated that overall microbial diversity promotes vitality and resilience, often leading to a healthier gut,” said Mathur, endocrinologist.
In the controlled study, researchers from the Cedars-Sinai Medically Associated Science and Technology (MAST) program compared the composition of gut microbes in male and female rats before, during, and after treatment with broad-spectrum antibiotics, including vancomycin, ampicillin, metronidazole and neomycin.
“We followed the rats for a period after the antibiotics were stopped and found that many of the sex-specific changes we observed during treatment remained. The constellation of microbes in the gut did not return to its original pre-antibiotic compositions in both sexes over the duration of the study,” said research associate Gonzalo Parodi, first author of the paper.
Some studies have identified sex-specific effects of antibiotics on the large intestine (feces) microbiome in mice. But the Cedars-Sinai researchers point out that this is the first study to also examine antibiotic-induced changes in the small intestine microbiome and to also use male and female rats which showed no significant differences. in the composition of the microbiome before treatment.
“It is difficult to determine the impact of drugs if the gut microbiomes of laboratory animals are different at baseline. We used rats with similar gut profiles from baseline. This allowed us to identify changes in microbiomes of male and female rats that could be attributed specifically to the impact of antibiotics during and after drug exposure,” said Mark Pimentel, MD, MAST program director and study co-author.
Further studies are needed using different combinations of antibiotics and exposure times. The researchers say if these findings hold true for humans, the research could have implications for how antibiotics are prescribed.
“Sex is a biological variable and, like any variable, it must be taken into account in basic and medical research. Currently, we take into account factors such as kidney function and weight when administering drugs to patients. According to the results of further research, specifically in humans, the gender of patients may one day be an important consideration when prescribing antibiotics,” said Mathur.