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Prevention of Non Communicable Diseases

GWAS-associated bacteria and their metabolites appear to be causally related to the development of inflammatory bowel disease

European Journal of Clinical Nutrition volume 76, pages 1024–1030 (2022)Cite this article

Subjects

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.

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Fig. 1: Flowchart of the data selection process.
Fig. 2: Potential pathways underpinning the relationship between gut microbiota and inflammatory bowel disease.
Fig. 3: Mendelian randomization study for gut metabolites and risk of IBD.

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Data availability

All data used in the present study were obtained from genome-wide association study summary statistics which were publicly released by genetic consortia.

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Acknowledgements

The PopGen 2.0 network (P2N) is supported by a grant from the German Federal Ministry for Education and Research (01EY1103). We thank Drs. Andre Franke and Wolfgang Lieb for sharing the GWAS summary data for beta diversity and bacterial abundance from published paper [21]. The study was supported by grants from the Peking University Start-up Grant (BMU2018YJ002), the National Key R&D Program of China (2020YFC2003401) and High-performance Computing Platform of Peking University. The funding organization had no role in the preparation of the manuscript.

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Author notes

  1. These authors contributed equally: Zhenhuang Zhuang, Nan Li.

Authors and Affiliations

  1. Department of Epidemiology & Biostatistics, School of Public Health, Peking University, 100191, Beijing, China

    Zhenhuang Zhuang, Nan Li, Ruotong Yang, Wenxiu Wang & Tao Huang

  2. Institute of Reproductive and Child Health/Chinese National Health Commission Key Laboratory of Reproductive Health, Peking University Health Science Center, Dongguan, China

    Nan Li

  3. Department of Pharmacy, Peking University First Hospital, Beijing, China

    Jiayi Wang

  4. Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong, China

    Zhonghua Liu

  5. Center for Intelligent Public Health, Academy for Artificial Intelligence, Peking University, 100191, Beijing, China

    Tao Huang

  6. Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, 100191, Beijing, China

    Tao Huang

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Contributions

ZZ, NL, and TH designed the research. ZZ and TH had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. ZZ, NL, ZL, and TH wrote the paper and performed the data analysis. All authors contributed to the statistical analysis, critically reviewed the manuscript during the writing process, and approved the final version to be published. ZZ and TH are the guarantors for the study.

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Correspondence to Tao Huang.

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Zhuang, Z., Li, N., Wang, J. et al. GWAS-associated bacteria and their metabolites appear to be causally related to the development of inflammatory bowel disease. Eur J Clin Nutr 76, 1024–1030 (2022). https://doi.org/10.1038/s41430-022-01074-w

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