Sexual dimorphism in the response to broad-spectrum antibiotics during T cell-mediated colitis.

Background: Broad spectrum antibiotics, including combination therapy with ciprofloxacin and metronidazole (Abx) are often prescribed during the treatment of IBD to alleviate symptoms, but with varying success. In this pilot study, we studied the effects of Abx in the course of experimental colitis, with a particular focus on sex as a determinant of the microbial and inflammatory responses.

Methods: The effects of Abx was tested on colonic inflammation and microbiome in male and female Rag-/- mice using adoptive transfer of naïve T cells to induce colitis in a short-term (two-week) and long-term (9-week) study.

Results: We observed disparities between sexes in both the response to adoptive T-cell transfer and the effects of Abx. At baseline, without Abx, female mice displayed a trend toward a more severe colitis than males. In both the short- and the long-term experiments, gut microbiota of some female mice exposed to Abx showed weak, delayed, or negligible shifts. Cecum weight was significantly lower in Abx-treated females. Abx exposure favored a quick and persistent rise in Enterococcaceae exclusively in females. Males had higher relative abundance of Lactobacillaceae following Abx exposure relative to females. Abx-treated females trended toward higher colitis scores than Abx-treated males, and towards higher levels of IL-17A, NOS2, and IL-22.

Conclusion: While preliminary, our results suggest a differential response to both inflammation and Abx between male and female mice, The findings may be relevant to current practice and as the basis for further studies on the differential gender effects during long term antibiotic exposure in IBD.