Inflammatory bowel disease (IBD) is a group of idiopathic and relapsing chronic inflammatory conditions of the gastrointestinal tract that are mainly represented by ulcerative colitis (UC) and Crohn's disease (CD) (1). Initially, Asia has been classified as an agricultural region with a low incidence of IBD for a long period (2, 3). However, compelling evidence from Ng et al. and other researchers has demonstrated a dramatic increase in the incidence of IBD in traditionally low-incidence regions across Asia (2, 4–11), where industrialization and urbanization have progressively been accelerated over the last three decades (12, 13). Historically, China was a traditional rural-agricultural social model country and over 90% of the land's population lived in rural areas for thousands of years. However, China has been undergoing rapid industrialization in the past 30 years, which is reflected in significantly increased gross domestic product (GDP) or GDP per capita. Together with urban-rural integration policies (14), fast industrialization may result in a high demand for factory labor and a considerable population migration from rural areas to cities (15). Studies showed that both industrialization and urbanization may take a toll on many aspects of the environment, i.e., crowding, increased air pollution and industrial waste, and work-related stress associated with poverty and unemployment (16). All these changes may contribute to the increasing risk for IBD in developing countries (10, 17). Because of its population size and rapid industrialization and urbanization speed, China represents an ideal model to study the relationship between industrialization/urbanization and IBD in developing countries. Previous studies have documented significant geographical variations in inflammatory bowel diseases (IBD) rates in China (10). The objectives of this review are to analyze the role of industrialization/urbanization, and subsequent environmental changes in geographical variation in IBD incidences in China and to discuss the potential role of these factors in contributing to the increasing risk for human IBD.

This review highlights the potential role of industrialization, urbanization, and relevant environmental risk factors in increasing IBD incidence in China and discuss the possible contributing factors on dramatically increasing incidence of IBD in newly industrialized and urbanized developing countries. By analyzing GDP or GDP per capita or populations in IBD epidemiological data available provinces, we were able to show different rates of IBD incidences in geographic regions with different level of industrialization and urbanization.

One of the key findings of current systematic analysis in this review is that incidences of IBD, UC and CD in the regions with high rates of industrialization and urbanization were higher than those regions with low rates. In the past 30 years, the rapid growth of Chinese GDP value mainly comes from the process of industrialization. Our analysis showed that the value of GDP per capita was better than GDP in order to be consistent with the changing trend of IBD in Chinese regions and might be a better index for industrialization because it excluded the influence of population added to provincial GDP. For example, the GDP of Sichuan Province was $377,819,000 and higher than that ($352,478,000) of Hubei Province in 2012. However, the value of GDP per capita in 2012 for Sichuan was $4,686/person and was lower than the value ($6,111/person) for Hubei Province. This was most likely because Sichuan Province had a larger population than Hubei Province. Analysis also showed that the IBD incidence in Shanxi (a province located in Central China) and with GDP per capita at a level of 6,108 US dollar was at a level of 0.54/100 000 (0.42 for UC and 0.07/100 000 for CD), which was much lower than that (IBD incidence 1.77, 1.64 for UC and 0.13/100 000 for CD) in Heilongjiang (a province located in Northern China). However, the value of GDP per capita in Shanxi province was slightly higher than that in Heilongjiang province (Shanxi vs. Heilongjiang: 6,108 vs. 5,657 US dollar). To explore the possible reasons for this inconsistency of IBD incidence between two provinces, we have further analyzed the composition of GDP for Shanxi and Heilongjiang provinces. We found that unlike provinces in Heilongjiang where GDP growth predominately comes from industries such as steel, oil and machine manufacturing that require a large number of workers. However, Shanxi is a province with abundant underground coal resources, it's GDP growth heavily relied on energy (coal) industry over the last three decades because the price of coal was gradually rising overtimes. Shanxi's coal production accounted 28% of Chinese coal production, which made Shanxi's coal industry as the biggest coal industry in China in 2000 (82). Due to highly automation in coal mining, most people in Shanxi were not involved in the coal industry. Therefore, the impact of industrialization on the people of Shanxi was not as big as it was on the people of Heilongjiang province, although the two provinces have a GDP per capita of about the same level. This phenomenon remains us that the differences in the GDP composition and variations in individuals should be considered, when GDP or GDP per capita is used as an solo index for industrialization level. In addition, the development of IBD is influenced by multiple factors. Shanxi is located in central China and is a region with profound Chinese traditional culture. In Shanxi, the traditional Chinese food habits are more preserved, which are reflected in more cereals, fibers, and vegetables, but less sugary foods and meats. Such diet components have been considered as protective factors for Chinese IBD (10, 25, 48). Furthermore, epidemiological studies confirmed a geographic variation in Chinese IBD incidences between southern and southwestern Chinese regions (10, 30), where different rates of industrialization and urbanization were observed (83). Finally, the incidence of IBD was increased with time and industrialization. Our analysis showed that the changing trend of IBD, UC and CD incidences in a 14-year (from 2000 to 2013) follow-up study was consistent with the step-up tendency of gross industry products in Yunnan Province (30). These analyses provided further supportive evidence for the hypothesis that industrialization is associated with the development of IBD.

Ongoing expanding industrialization and China's urban-rural integration policies might result in accelerated urban population recruitment (15). Studies have shown that fast accelerated industrialization and urbanization in China may lead to a remarkable change in the dietary pattern between urban and rural regions in the past three decades, and Westernized food has become popular in urban areas (50). A Westernized diet high in fat and carbohydrates and low in fiber is implicated in the increasing incidence of IBD (81). Traditionally, Chinese daily food intake contains high cereals and legumes and many vegetables and fibers but less fat, meat, and milk. However, current Chinese diet recipes have been skewed in a Westernized style (60). Such food intake and nutrient change could induce overweight/obesity in both Chinese children and adults (50, 60). In contrast to the report from Chinese children, a systematic analysis from the United States showed that higher rates of overweight and obesity were often found among American children living in rural areas than children in urban areas (84). Such inconsistent conclusions might reflect the difference in dietary composition and economic level between Chinese and American rural families. The economic level of Chinese families was generally lower than that of American families living in rural areas. In addition, many rural Chinese families still retain more traditional diet habits and consume less fat, red meat and milk but eat more vegetables, fruits, and cereals than urban families today.

The gut microbiota profile alteration has been demonstrated in both Chinese and Western patients with IBD. Scientific evidence has strongly indicated that environmental factors such as diet can modulate the composition and function of gut microbiota and intestinal homeostasis (85), which is associated with the onset and development of IBD. Interestingly, a study reported that compositional patterns of abundant microbes in the urban Chinese population become Westernized and similar to those in the urban American population, which was hypothesized to be induced by urbanization (37). Furthermore, researchers found that Italian children who consumed a typical Western diet had a much less diverse microbiome than African children who consumed mainly legumes, grains and vegetables (86). These findings supported the hypothesis that the gut microbiota profile can be regulated by environmental factors and have opened a new opportunity for a therapeutic strategy through modulating the gut microbiota profiles by diet, probiotics, and fecal microbiota transplantation to improve the clinical outcomes in patients with IBD.

Finally, two studies reported that work-related stress increased the risk for Chinese UC (30, 33), which needs further confirmation.

Limitations and challenges should be addressed and discussed. First, China is a big country with hugged population. The level of industrialization and urbanization varies cross the country. To better interpret the influence of urbanization on IBD incidence, it is better to make a figure to show the IBD gradient along with urbanization/migration across the country. However, current epidemiological studies of Chinese IBD incidence are not nationwide population-based studies and only available in several provinces. Therefore, we were unable to analyze the gradient changes of IBD incidence along with urbanization that covers most provinces of China. Second, the role of industrial risk factors such as wastewater and air pollution have not been evaluated in Chinese IBD populations. Therefore, the most urgent task is to conduct a continuous nationwide epidemiological survey as soon as possible, which might address these concerns.

When summarizing the existing clinical epidemiological data in this review, a strong body of evidence suggested that the dramatically increasing incidence of IBD in traditionally low-incidence Chinese regions can be, at least in partially, explained by industrialization, urbanization and subsequent changed environmental factors (see Figure 3). However, current Chinese epidemiological studies are not nationwide population-based studies and are limited by small sample sizes and lack of robust longitudinal follow-up. Therefore, the most urgent task is to conduct a continuous nationwide epidemiological survey as soon as possible. Furthermore, to explore the reasons for geographical variation in IBD in Chinese regions with different industrialized and urbanized levels, future efforts should be focused on examining the effects of other environmental changes induced by industrialization, such as water and air pollution, on IBD susceptibility genes. Finally, since the composition and function of gut microbiota can be regulated by environmental factors, the effect of modifying the gut microbiota profile through diet and probiotics in newly industrialized and urbanized regions should be considered.

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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