Scientists at Cedars-Sinai discovered that antibiotics have sex-specific effects on the gut microbiome makeup of male and female laboratory rats in a new study. The research results, which were published in the journal Frontiers in Microbiology, may have significance for using medications to treat or prevent bacterial infection in humans.
We found that giving the rats a multidrug antibiotic cocktail resulted in significant and sex-specific changes in both the stool, or large intestine, and the small bowel. For example, greater loss of the diversity of the microbes in both stool and small bowel was observed in the male rodents than in the females.”
Ruchi Mathur, MD, Study Principal Investigator
“Changes in the diversity of the gut microbiome could have a negative impact. Previous studies of intestinal health have demonstrated that overall microbial diversity promotes vitality and resilience, often making for a healthier gut,” said Mathur, an endocrinologist.
The Cedars-Sinai Medically Associated Science and Technology (MAST) Program researchers compared the structure of the gut microbes of male and female rats before, during, and after cure with broad-spectrum antibiotics like 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 their original, pre-antibiotic compositions in either sex during the duration of the study,” said research associate Gonzalo Parodi, first author of the paper.
Some studies have found that antibiotics have sex-specific effects on the large bowel (stool) microbiome in mice. However, the Cedars-Sinai researchers emphasize that this is the first research to look at changes in the small bowel microbiome caused by antibiotics, as well as the first to use male and female rats with no major differences in microbiome before the procedure.
“It is difficult to tease out the impact of the drugs if the lab animals’ gut microbiomes are different to begin with. We used rats with similar gut profiles right out of the gate. This allowed us to pinpoint changes in the microbiomes of the male and female rats that could be attributed specifically to the impact of the antibiotics during and after exposure to the medicines,” said Mark Pimentel, MD, director of the MAST program and a co-author of the study.
More research on different antibiotic combinations and exposure times is required. According to the researchers, if these research results hold true in humans, the study could affect how antibiotics are prescribed.
Sex is a biological variable, and like any variable, it needs to be taken into consideration in basic and medical research. Currently, we consider factors such as kidney function and weight when dosing medications for patients. Depending on the results of further research, specifically in humans, the sex of patients may one day be an important consideration when prescribing antibiotics.”
Ruchi Mathur, MD, Study Principal Investigator
Source:
Journal reference:
Parodi, G., et al. (2022) The Response of the Rodent Gut Microbiome to Broad-Spectrum Antibiotics Is Different in Males and Females. Frontiers in Microbiology. doi.org/10.3389/fmicb.2022.897283.