Haberman Ziv, Y.(1)*;Feng, R.(2);Mao, R.(2);Braun, T.(1);Zhuo, S.(2);Toren, I.(1);Efroni, G.(1);Malik, A.(3);Picard, O.(3);Yavzori, M.(3);Hadar, R.(1);Amir, A.(1);Chen, M.(2);Ben-Horin, S.(3);
(1)Sheba Medical Center, Pediatric Gastroenterology, Ramat Gan, Israel;(2)The First Affiliated Hospital- Sun Yat-Sen University, Gastroenterology, Guangzhou, China;(3)Sheba Medical Center, Gastroenterology, Ramat Gan, Israel;
The Leona M. and Harry B. Helmsley Charitable Trust SOURCE consortium investigators
Efforts to delineate factors linked with rural to urban transition, paralleling the staggering rise in CD incidence, have been hampered by the universal modernization in the west. China is ongoing transition from a predominantly traditional rural to an urban and industrialized society. We aimed to study the effect of changes and their relationship to CD.
SOURCE characterized environmental exposures, diet, and microbiome in rural and urban genetically similar Chinese controls and newly diagnosed CD in Guangdong province, and in Israeli CD and controls
380 subjects (median age 34years, 51% males); 40 CD and 162 rural controls and 121 urban controls from China, and 25 CD and 32 controls from Israel. Significant factors affecting the gut microbial composition were identified using PERMANOVA including the amount of time spent in urban area, dietary consumption of fat, fruits, iron, and added sugar, and exposures to farm animals. As the amount of time spent in urban area was linked with microbial composition, we stratified subjects living in rural area to those spending<50% of their time in the last year in urban areas ('rural', n=88) and those living in rural area but spending³50% of their time in urban environment ('rural-urban’, n=74) and compared then to the city-dwellers ('urban', n=121). Environmental exposures differed (Fig. 1) whereby flush toilet availability was reported in 5% rural, 35% rural-urban, and 61% urban, and 100% of Israelis. Having farm animals was noted in 60% rural, 24% rural-urban, and 3% of urban. Dietary habits also differed substantially; drinking at least weekly soft drink was reported in 5% rural and 27% of urban Chinese subjects, and 60% of the Israeli controls, while coffee was reported in 1% of rural, 15% of rural-urban, 32% urban, and 77% of Israelis. UniFrac-based PCoA indicated separation between rural and rural-urban control samples, with differences in β diversity (Fig. 2). Additionally, a-diversity was lower in rural-urban vs. rural controls, and in CD vs. urban cases. Composing a rural index based on an independent cohort (PMID:28915922) also indicated reduced rural index in rural-urban vs. rural controls, and in CD vs. urban cases. Using another independent health microbial index (PMID:35197084) also indicated reduced health index in rural-urban vs. rural controls, and in CD vs. urban cases (Fig. 2).
Trajectory of rural-urban transition is continuous and not dichotomous, whereby time spent in urban area associates with diet, exposures, and gut microbial composition. Living in rural area but spending ³50% of daily-life in urban environment (rural-urban) is linked with reduction in a-diversity, reduced rural index, and reduced microbial health index mirroring CD profile.