Header

UZH-Logo

Maintenance Infos

Loss of PTPN22 abrogates the beneficial effect of cohousing-mediated fecal microbiota transfer in murine colitis


Spalinger, Marianne R; Schwarzfischer, Marlene; Hering, Larissa; Shawki, Ali; Sayoc, Anica; Santos, Alina; Gottier, Claudia; Lang, Silvia; Bäbler, Katharina; Geirnaert, Annelies; Lacroix, Christophe; Leventhal, Gabriel E; Dai, Xuezhi; Rawlings, David; Chan, Andrew A; Rogler, Gerhard; McCole, Declan F; Scharl, Michael (2019). Loss of PTPN22 abrogates the beneficial effect of cohousing-mediated fecal microbiota transfer in murine colitis. Mucosal Immunology, 12(6):1336-1347.

Abstract

Fecal microbiota transfer (FMT) is a very efficient approach for the treatment of severe and recurring C. difficile infections. However, the beneficial effect of FMT in other disorders such as ulcerative colitis (UC) or Crohn's disease remains unclear. Furthermore, it is currently unknown how disease-associated genetic variants in donors or recipients influence the effect of FMT. We found that bacteria-transfer from wild-type (WT) donors via cohousing was efficient in inducing recovery from colitis in WT mice, but not in mice deficient in protein-tyrosine phosphatase non-receptor type 22 (PTPN22), a known risk gene for several chronic inflammatory diseases. Also cohousing of PTPN22-deficient mice with diseased WT mice failed to induce faster recovery. Our data indicate that the genetic background of the donor and the recipient influences the outcome of microbiota transfer, and offers a potential explanation why transfer of fecal microbes from some, but not all donors is efficient in UC patients.

Abstract

Fecal microbiota transfer (FMT) is a very efficient approach for the treatment of severe and recurring C. difficile infections. However, the beneficial effect of FMT in other disorders such as ulcerative colitis (UC) or Crohn's disease remains unclear. Furthermore, it is currently unknown how disease-associated genetic variants in donors or recipients influence the effect of FMT. We found that bacteria-transfer from wild-type (WT) donors via cohousing was efficient in inducing recovery from colitis in WT mice, but not in mice deficient in protein-tyrosine phosphatase non-receptor type 22 (PTPN22), a known risk gene for several chronic inflammatory diseases. Also cohousing of PTPN22-deficient mice with diseased WT mice failed to induce faster recovery. Our data indicate that the genetic background of the donor and the recipient influences the outcome of microbiota transfer, and offers a potential explanation why transfer of fecal microbes from some, but not all donors is efficient in UC patients.

Statistics

Citations

Altmetrics

Downloads

10 downloads since deposited on 10 Jan 2020
10 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:November 2019
Deposited On:10 Jan 2020 14:25
Last Modified:10 Jan 2020 14:26
Publisher:Nature Publishing Group
ISSN:1933-0219
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41385-019-0201-1
PubMed ID:31501515

Download

Green Open Access

Download PDF  'Loss of PTPN22 abrogates the beneficial effect of cohousing-mediated fecal microbiota transfer in murine colitis'.
Preview
Content: Published Version
Filetype: PDF
Size: 3MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)