BACKGROUND: Broad-spectrum antibiotics [Abx], including combination therapy with ciprofloxacin and metronidazole, are often prescribed during the treatment of inflammatory bowel disease [IBD] to alleviate symptoms, but with varying success. In this pilot study, we studied the effects of Abx on 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 were 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 [2-week] and long-term [9-week] study. RESULTS: We observed disparities between the 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. Caecum weight was significantly lower in Abx-treated females. Abx exposure favoured 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. CONCLUSIONS: Although 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 also as the basis for further studies on the differential gender effects during long-term antibiotic exposure in IBD.
BACKGROUND: Broad-spectrum antibiotics [Abx], including combination therapy with ciprofloxacin and metronidazole, are often prescribed during the treatment of inflammatory bowel disease [IBD] to alleviate symptoms, but with varying success. In this pilot study, we studied the effects of Abx on 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 were 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 [2-week] and long-term [9-week] study. RESULTS: We observed disparities between the 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. Caecum weight was significantly lower in Abx-treated females. Abx exposure favoured 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. CONCLUSIONS: Although 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 also as the basis for further studies on the differential gender effects during long-term antibiotic exposure in IBD.
Authors: Emma L Armitage; Marian C Aldhous; Niall Anderson; Hazel E Drummond; Rudolph A Riemersma; Subrata Ghosh; Jack Satsangi Journal: Gastroenterology Date: 2004-10 Impact factor: 22.682
Authors: H J van der Zaag-Loonen; M Casparie; J A J M Taminiau; J C Escher; R Rodrigues Pereira; H H F Derkx Journal: J Pediatr Gastroenterol Nutr Date: 2004-03 Impact factor: 2.839
Authors: Subra Kugathasan; Robert H Judd; Raymond G Hoffmann; Janice Heikenen; Gregorz Telega; Farhat Khan; Sally Weisdorf-Schindele; William San Pablo; Jean Perrault; Roger Park; Michael Yaffe; Christopher Brown; Maria T Rivera-Bennett; Issam Halabi; Alfonso Martinez; Ellen Blank; Steven L Werlin; Colin D Rudolph; David G Binion Journal: J Pediatr Date: 2003-10 Impact factor: 4.406
Authors: Mark E Obrenovich; George E Jaskiw; Thriveen Sankar Chittoor Mana; Christina P Bennett; Jennifer Cadnum; Curtis J Donskey Journal: Pathog Immun Date: 2019-11-14