Association study between intestinal microbiota dysbiosis in inflammatory bowel disease and the global disease burden growth trend

Background Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a group of chronic intestinal inflammatory diseases. Its incidence and prevalence have been on the rise globally, imposing a heavy burden on patients’ health and social medical resources. Intestinal microbiota dysbiosis is believed to play a crucial role in the occurrence and development of IBD, but the association between them and the global disease burden growth trend remains unclear. Methods By searching the Global Burden of Disease (GBD) study database, we collected IBD disease burden data from 180 countries and regions between 1990 and 2023, including key indicators such as incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Intestinal microbiota data were sourced from two parts: (1) Independent collection: A total of 20,000 healthy individuals and IBD patients were selected as research subjects from 180 countries and regions using a stratified random sampling method. Fecal samples (2–5 grams per person) were collected and immediately stored in a −80 °C ultra-low temperature refrigerator to avoid changes in the microbial community structure; (2) Supplementary data from public databases: Published intestinal microbiota sequencing data of corresponding regions from 1990 to 2023 were extracted from the MGnify ( https://www.ebi.ac.uk/metagenomics/ ), Human Microbiome Project (HMP), and GMrepo ( https://gmrepo.humangut.info/ ) databases. The sample size for each country and region was no less than 500 to cover populations of different ages (18–70 years), genders (male/female ratio approximately 1:1), and dietary habits (high-fiber diet, high-sugar and high-fat diet). Technologies like metagenomic sequencing and 16S rRNA gene sequencing were used to obtain data on the composition, abundance, and diversity of the intestinal microbiota of the corresponding regional populations. For metagenomic sequencing, the Illumina HiSeq or NovaSeq platform was used. Linear regression models, time-series analysis, and causal inference methods were applied to evaluate the correlation between intestinal microbiota dysbiosis and the growth trends of various disease burden indicators, and to explore the potential impact mechanisms. Results The global incidence of IBD increased from 12.3 per 100,000 in 1990 to 25.6 per 100,000 in 2023, the prevalence rose from 396 per 100,000 to 523 per 100,000, and the DALY value also increased significantly (from 230 per 100,000 in 1990 to 380 per 100,000 in 2023). The average annual growth rates of the above indicators were 2.8% (95% CI: 2.5–3.1%, p < 0.001), 1.0% (95% CI: 0.8–1.2%, p < 0.001), and 1.5% (95% CI: 1.3–1.7%, p < 0.001), respectively. Further analysis showed that intestinal microbiota dysbiosis was closely related to the growth of the disease burden. In regions with severe microbiota dysbiosis, the annual growth rate of the IBD incidence was 3.2 times higher than that in balanced regions ( β = 3.2, 95% CI: 2.8–3.6, p < 0.001); when the average abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus in the intestine decreased by 40% (relative to the average abundance of healthy populations) and the abundance of harmful bacteria such as Escherichia coli increased by 60%, the annual growth rate of IBD incidence in this region was as high as 8.5% (95% CI: 7.9–9.1%, p < 0.001); in regions where the Shannon index decreased by 10%, the incidence of IBD increased by an average of 15% ( β = 0.15, 95% CI: 0.12–0.18, p < 0.001). A positive correlation was observed between the degree of intestinal microbiota dysbiosis and disease severity (measured by DALYs): in regions where the intestinal F/B ratio deviated from the normal range by more than 30%, DALYs were 40% higher than those in regions with a normal ratio ( β = 0.40, 95% CI: 0.35–0.45, p < 0.001); in regions where the content of short-chain fatty acids (SCFAs) decreased by 20%, DALYs increased by approximately 25% ( β = 0.25, 95% CI: 0.21–0.29, p < 0.001). Among IBD patients with different severity levels in the Asian region, the abundance of specific bacterial genera related to inflammation regulation (e.g., Faecalibacterium ) in the intestines of severe patients decreased by more than 50% compared with healthy populations, and their DALY values were 60% higher than those of mild patients (95% CI: 55–65%, p < 0.001). Additionally, the SCFA levels of severe patients were significantly lower than those of mild patients and healthy populations (median SCFA level: 2.1 mmol/L in severe patients; 4.5 mmol/L in mild patients; 6.8 mmol/L in healthy populations, p < 0.001). Conclusion This study confirms a close association between intestinal microbiota dysbiosis in inflammatory bowel disease and the global disease burden growth trend. Intestinal microbiota dysbiosis can be used as a key indicator to predict the growth of the IBD disease burden, providing an important theoretical basis for formulating targeted prevention, control strategies, and treatment methods.