Zhenhuang Zhuang1, Nan Li1,2, Jiayi Wang3, Ruotong Yang1, Wenxiu Wang1, Zhonghua Liu4, Tao Huang5,6,7. 1. Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 100191, Beijing, China. 2. Institute of Reproductive and Child Health/Chinese National Health Commission Key Laboratory of Reproductive Health, Peking University Health Science Center, Dongguan, China. 3. Department of Pharmacy, Peking University First Hospital, Beijing, China. 4. Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong, China. 5. Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 100191, Beijing, China. huangtaotao@pku.edu.cn. 6. Center for Intelligent Public Health, Academy for Artificial Intelligence, Peking University, 100191, Beijing, China. huangtaotao@pku.edu.cn. 7. Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, 100191, Beijing, China. huangtaotao@pku.edu.cn.
Abstract
BACKGROUND: Accumulating evidence has suggested that the imbalance of gut microbiota is commonly observed in patients with inflammatory bowel disease (IBD). However, it remains unclear whether dysbiosis is a cause or consequence of chronic intestinal inflammation. We aimed to investigate the causal relationships of gut microbiota and metabolites with IBD, including ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We applied two-sample Mendelian randomization using summary statistics from the gut microbiota genetic consortium (n = 1812), the Framingham Heart Study (n = 2076) and the International IBD Genetics Consortium (n = 86,640). RESULTS: Using the genetic approach, the increase in OTU10032 unclassified Enterobacteriaceae was associated with higher risks of IBD (OR, 1.03; 95% CI, 1.00-1.06; P = 0.033) and CD (1.04; 1.01-1.08; P = 0.015). Importantly, an Enterobacteriaceae-related metabolite taurine was positively associated with risks of IBD (1.04; 1.01-1.08; P = 0.016) and UC (1.05; 1.01-1.10; P = 0.024). Notably, we also found betaine, a downstream product of Enterobacteriaceae metabolism, was causally associated with a higher risk of CD (1.10; 1.02-1.18; P = 0.008). In addition, increased Erysipelotrichaceae family were causally related to lower risks of IBD (0.88; 0.78-0.98; P = 0.026) and UC (0.86; 0.75-0.99; P = 0.042), and Actinobacteria class (0.80; 0.65-0.98; P = 0.028) and Unclassified Erysipelotrichaceae (0.79; 0.64-0.98; P = 0.036) were associated with lower risks of UC and CD, respectively. CONCLUSIONS: Our finding provided new insights into the key role of gut metabolites such as taurine and betaine in host-microbiota interactions of IBD pathogenesis, indicating that host-microbe balance strongly influences inflammatory conditions.
BACKGROUND: Accumulating evidence has suggested that the imbalance of gut microbiota is commonly observed in patients with inflammatory bowel disease (IBD). However, it remains unclear whether dysbiosis is a cause or consequence of chronic intestinal inflammation. We aimed to investigate the causal relationships of gut microbiota and metabolites with IBD, including ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We applied two-sample Mendelian randomization using summary statistics from the gut microbiota genetic consortium (n = 1812), the Framingham Heart Study (n = 2076) and the International IBD Genetics Consortium (n = 86,640). RESULTS: Using the genetic approach, the increase in OTU10032 unclassified Enterobacteriaceae was associated with higher risks of IBD (OR, 1.03; 95% CI, 1.00-1.06; P = 0.033) and CD (1.04; 1.01-1.08; P = 0.015). Importantly, an Enterobacteriaceae-related metabolite taurine was positively associated with risks of IBD (1.04; 1.01-1.08; P = 0.016) and UC (1.05; 1.01-1.10; P = 0.024). Notably, we also found betaine, a downstream product of Enterobacteriaceae metabolism, was causally associated with a higher risk of CD (1.10; 1.02-1.18; P = 0.008). In addition, increased Erysipelotrichaceae family were causally related to lower risks of IBD (0.88; 0.78-0.98; P = 0.026) and UC (0.86; 0.75-0.99; P = 0.042), and Actinobacteria class (0.80; 0.65-0.98; P = 0.028) and Unclassified Erysipelotrichaceae (0.79; 0.64-0.98; P = 0.036) were associated with lower risks of UC and CD, respectively. CONCLUSIONS: Our finding provided new insights into the key role of gut metabolites such as taurine and betaine in host-microbiota interactions of IBD pathogenesis, indicating that host-microbe balance strongly influences inflammatory conditions.
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