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Abstract
Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions.
Exposures rather than genetics likely contribute to the worldwide increased prevalence of Crohn Disease (CD). Here, the authors constructed the Study Of Urban and Rural Crohn disease Evolution (SOURCE), a multicenter and multi-omics cross-sectional study, to identify that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirrored those seen in CD. Reviewer recognition:
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1 Tel-Hashomer, Affiliated with the Tel Aviv University, Sheba Medical Center, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546)
2 Sun Yat-Sen University, The First Affiliated Hospital, Guangzhou, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X); Sun Yat-Sen University, Department of Gastroenterology, Guangxi Hospital Division of The First Affiliated Hospital, Nanning, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X)
3 Tel-Hashomer, Affiliated with the Tel Aviv University, Sheba Medical Center, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546); Tel Aviv University, Faculty of Medical and Health Sciences, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546)
4 Sun Yat-Sen University, The First Affiliated Hospital, Guangzhou, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X)
5 Tel-Hashomer, Affiliated with the Tel Aviv University, Sheba Medical Center, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546); Hebrew University of Jerusalem, Department of Military Medicine, Faculty of Medicine, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538)
6 Tel Aviv University, Faculty of Medical and Health Sciences, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546)
7 Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer, Israel (GRID:grid.413795.d) (ISNI:0000 0001 2107 2845)
8 Bat Galim, Laura and Isaac Perlmutter Metabolomics Center, Technion-Israel Institute of Technology, Haifa, Israel (GRID:grid.6451.6) (ISNI:0000 0001 2110 2151)
9 Washington University in St Louis School of Medicine, Department of Pathology and Immunology, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002)
10 Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725)
11 University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, Cincinnati, USA (GRID:grid.24827.3b) (ISNI:0000 0001 2179 9593)
12 Tel Aviv University, Faculty of Medical and Health Sciences, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546); Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer, Israel (GRID:grid.413795.d) (ISNI:0000 0001 2107 2845)
13 Bat Galim, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel (GRID:grid.6451.6) (ISNI:0000 0001 2110 2151)
14 Tel Aviv University, Faculty of Medical and Health Sciences, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546); Tel Aviv University, Blavatnik School of Computer Science, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546); Santa Fe Institute, Santa Fe, USA (GRID:grid.209665.e) (ISNI:0000 0001 1941 1940)
15 Weizmann Institute of Science, Department of Systems Immunology, Rehovot, Israel (GRID:grid.13992.30) (ISNI:0000 0004 0604 7563); German National Cancer Center (DKFZ), Microbiome & Cancer Division, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584)
16 Tel-Hashomer, Affiliated with the Tel Aviv University, Sheba Medical Center, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546); Tel Aviv University, Faculty of Medical and Health Sciences, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546); University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, Cincinnati, USA (GRID:grid.24827.3b) (ISNI:0000 0001 2179 9593)