Sexual Dimorphism in the Response to Broad-spectrum Antibiotics During T Cell-mediated Colitis

Christy A. Harrison, Daniel Laubitz, Monica T. Midura-Kiela, Deepa R. Jamwal, David G. Besselsen, Fayez K Ghishan, Pawel R Kiela

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)115-126
Number of pages12
JournalJournal of Crohn's & colitis
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Colitis
Sex Characteristics
Anti-Bacterial Agents
T-Lymphocytes
Adoptive Transfer
Inflammatory Bowel Diseases
Lactobacillaceae
Enterococcaceae
Inflammation
Interleukin-17
Microbiota
Metronidazole
Ciprofloxacin
Weights and Measures
Therapeutics

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Sexual Dimorphism in the Response to Broad-spectrum Antibiotics During T Cell-mediated Colitis. / Harrison, Christy A.; Laubitz, Daniel; Midura-Kiela, Monica T.; Jamwal, Deepa R.; Besselsen, David G.; Ghishan, Fayez K; Kiela, Pawel R.

In: Journal of Crohn's & colitis, Vol. 13, No. 1, 01.01.2019, p. 115-126.

Research output: Contribution to journalArticle

Harrison, Christy A. ; Laubitz, Daniel ; Midura-Kiela, Monica T. ; Jamwal, Deepa R. ; Besselsen, David G. ; Ghishan, Fayez K ; Kiela, Pawel R. / Sexual Dimorphism in the Response to Broad-spectrum Antibiotics During T Cell-mediated Colitis. In: Journal of Crohn's & colitis. 2019 ; Vol. 13, No. 1. pp. 115-126.
@article{81097a81fdb344b4a239ccf0d09bd09e,
title = "Sexual Dimorphism in the Response to Broad-spectrum Antibiotics During T Cell-mediated Colitis",
abstract = "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 na{\"i}ve 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.",
author = "Harrison, {Christy A.} and Daniel Laubitz and Midura-Kiela, {Monica T.} and Jamwal, {Deepa R.} and Besselsen, {David G.} and Ghishan, {Fayez K} and Kiela, {Pawel R}",
year = "2019",
month = "1",
day = "1",
doi = "10.1093/ecco-jcc/jjy144",
language = "English (US)",
volume = "13",
pages = "115--126",
journal = "Journal of Crohn's and Colitis",
issn = "1873-9946",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Sexual Dimorphism in the Response to Broad-spectrum Antibiotics During T Cell-mediated Colitis

AU - Harrison, Christy A.

AU - Laubitz, Daniel

AU - Midura-Kiela, Monica T.

AU - Jamwal, Deepa R.

AU - Besselsen, David G.

AU - Ghishan, Fayez K

AU - Kiela, Pawel R

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85058922500&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058922500&partnerID=8YFLogxK

U2 - 10.1093/ecco-jcc/jjy144

DO - 10.1093/ecco-jcc/jjy144

M3 - Article

C2 - 30252029

AN - SCOPUS:85058922500

VL - 13

SP - 115

EP - 126

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

SN - 1873-9946

IS - 1

ER -