Identification of environmental factors that promote intestinal inflammation

Nature. 2022 Nov;611(7937):801-809. doi: 10.1038/s41586-022-05308-6. Epub 2022 Oct 20.


Liliana M Sanmarco # 1Chun-Cheih Chao # 1Yu-Chao Wang # 2Jessica E Kenison # 1Zhaorong Li 1Joseph M Rone 1Claudia M Rejano-Gordillo 1Carolina M Polonio 1Cristina Gutierrez-Vazquez 1Gavin Piester 1 3Agustin Plasencia 1Lucinda Li 1Federico Giovannoni 1Hong-Gyun Lee 1Camilo Faust Akl 1Michael A Wheeler 1 4Ivan Mascanfroni 1Merja Jaronen 1Moneera Alsuwailm 1Patrick Hewson 1Ada Yeste 1Brian M Andersen 1 5Diana G Franks 6Chien-Jung Huang 2Millicent Ekwudo 1Emily C Tjon 1Veit Rothhammer 1Maisa Takenaka 1Kalil Alves de Lima 1Mathias Linnerbauer 1Lydia Guo 1Ruxandra Covacu 1Hugo Queva 1Pedro Henrique Fonseca-Castro 1Maha Al Bladi 1Laura M Cox 1Kevin J Hodgetts 1Mark E Hahn 6Alexander Mildner 7Joshua Korzenik 8Russ Hauser 9Scott B Snapper 10 11Francisco J Quintana 12 13


Author information

1Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

2Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan.

3Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.

4The Broad Institute of Harvard and MIT, Cambridge, MA, USA.

5Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

6Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA, USA.

7Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany.

8Department of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

9Harvard T. H. Chan School of Public Health, Boston, MA, USA.

10Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA.

11Department of Medicine, Harvard Medical School, Boston, MA, USA.

12Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. fquintana@rics.bwh.harvard.edu.

13The Broad Institute of Harvard and MIT, Cambridge, MA, USA. fquintana@rics.bwh.harvard.edu.

#Contributed equally.


Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD)1-a complex chronic inflammatory disorder of the gastrointestinal tract. The increasing prevalence of IBD in industrialized countries and the augmented disease risk observed in migrants who move into areas of higher disease prevalence suggest that environmental factors are also important determinants of IBD susceptibility and severity2. However, the identification of environmental factors relevant to IBD and the mechanisms by which they influence disease has been hampered by the lack of platforms for their systematic investigation. Here we describe an integrated systems approach, combining publicly available databases, zebrafish chemical screens, machine learning and mouse preclinical models to identify environmental factors that control intestinal inflammation. This approach established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we show that an AHR-NF-κB-C/EBPβ signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline for the identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases.



© Copyright 2013-2024 GI Health Foundation. All rights reserved.
This site is maintained as an educational resource for US healthcare providers only. Use of this website is governed by the GIHF terms of use and privacy statement.