The Response of the Rodent Gut Microbiome to Broad-Spectrum Antibiotics Is Different in Males and Females

Abstract

Gut microbiome composition is different in males and females, but sex is rarely considered when prescribing antibiotics, and sex-based differences in gut microbiome recovery following antibiotic treatment are poorly understood. Here, we compared the effects of broad-spectrum antibiotics on both the stool and small bowel microbiomes in male and female rats. Adult male and female Sprague Dawley rats were exposed to a multi-drug antibiotic cocktail for 8 days, or remained unexposed as controls. Following cessation of antibiotics, rats were monitored for an additional 13-day recovery period prior to euthanasia. Baseline stool microbiome composition was similar in males and females. By antibiotic exposure day 8 (AbxD8), exposed male rats exhibited greater loss of stool microbial diversity compared to exposed females, and the relative abundance (RA) of numerous taxa were significantly different in exposed males vs. exposed females. Specifically, RA of phylum Proteobacteria and genera Lactobacillus, Sutterella, Akkermansia, and Serratia were higher in exposed males vs. exposed females, whereas RA of phyla Firmicutes and Actinobacteria and genera Turicibacter and Enterococcus were lower. By 13 days post antibiotics cessation (PAbxD13), the stool RA of these and other taxa remained significantly different from baseline, and also remained significantly different between exposed males and exposed females. RA of phyla Firmicutes and Actinobacteria and genus Enterococcus remained lower in exposed males vs. exposed females, and genus Sutterella remained higher. However, RA of phylum Proteobacteria and genus Akkermansia were now also lower in exposed males vs. females, whereas RA of phylum Bacteroidetes and genus Turicibacter were now higher in exposed males. Further, the small bowel microbiome of exposed rats on PAbxD13 was also significantly different from unexposed controls, with higher RA of Firmicutes, Turicibacter and Parabacteroides in exposed males vs. females, and lower RA of Bacteroidetes, Proteobacteria, Actinobacteria, Oscillospira, Sutterella, and Akkermansia in exposed males vs. females. These findings indicate that broad-spectrum antibiotics have significant and sex-specific effects on gut microbial populations in both stool and the small bowel, and that the recovery of gut microbial populations following exposure to broad-spectrum antibiotics also differs between sexes. These findings may have clinical implications for the way antibiotics are prescribed.

Host microbiome depletion attenuates biofluid metabolite responses following radiation exposure

“…Plasma levels of hippuric acid, indole-3-acetic acid, amino acids, and glycerol in rats were perturbed across several antibiotic classes while changes in indoxyl sulfate was associated with tetracyclines [42], however, we found in the current study urinary levels of indoxyl sulfate are heavily affected by a combination of a fluoroquinolone (enrofloxacin) and ampicillin as well. While sex differences are observed in the normal gut microbiota [44], differential response to antibiotics have also been observed in Sprague Dawley rats given a mixture of vancomycin, ampicillin, neomycin, and metronidazole [45]. Male rats showed an increased loss of microbial diversity than females in the stool, the relative abundance of Lactobacillus, Akkermansia, Serratia, and Sutterrella was higher in male stool [45].…”

“…While sex differences are observed in the normal gut microbiota [44], differential response to antibiotics have also been observed in Sprague Dawley rats given a mixture of vancomycin, ampicillin, neomycin, and metronidazole [45]. Male rats showed an increased loss of microbial diversity than females in the stool, the relative abundance of Lactobacillus, Akkermansia, Serratia, and Sutterrella was higher in male stool [45]. Although changes in the microbiome can be treatment and sex specific, we find several similarities across previous studies using this broad-spectrum antibiotic mixture, which induced changes in several metabolic pathways including tryptophan and amino acid metabolism, bile secretion, and steroid hormone biosynthesis.…”

“…Not all microbes will be eliminated using antibiotic treatments and there can be sex-effects as observed in the current study. Future studies may use a microbiome profiling approach to determine which microorganisms are present after this particular antibiotic regimen and how this would be different between males and females, as has been observed in a Sprague Dawley rat model [45]. Also, the use of a single metabolomics platform (here LC/MS) will not capture the whole metabolome.…”

Microbiome Dynamics: A Paradigm Shift in Combatting Infectious Diseases

“…Different microorganisms within the microbiome possess varying degrees of resistance or susceptibility to specific drugs. By analyzing an individual's microbiome profile, healthcare professionals can predict drug responses and select appropriate antibiotics or antivirals that are more likely to be effective against the specific pathogens present [321,322]. This personalized approach can minimize the risk of treatment failure or adverse drug reactions, leading to improved therapeutic outcomes.…”