The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Human gut bacterial metabolism drives Th17 activation and colitis
Open accessAbstract
Bacterial activation of T helper 17 (Th17) cells exacerbates mouse models of autoimmunity, but how human-associated bacteria impact Th17-driven disease remains elusive. We show that human gut Actinobacterium Eggerthella lenta induces intestinal Th17 activation by lifting inhibition of the Th17 transcription factor Rorγt through cell- and antigen-independent mechanisms. E. lenta is enriched in inflammatory bowel disease (IBD) patients and worsens colitis in a Rorc-dependent manner in mice. Th17 activation varies across E. lenta strains, which is attributable to the cardiac glycoside reductase 2 (Cgr2) enzyme. Cgr2 is sufficient to induce interleukin (IL)-17a, a major Th17 cytokine. cgr2+ E. lenta deplete putative steroidal glycosides in pure culture; related compounds are negatively associated with human IBD severity. Finally, leveraging the sensitivity of Cgr2 to dietary arginine, we prevented E. lenta-induced intestinal inflammation in mice. Together, these results support a role for human gut bacterial metabolism in driving Th17-dependent autoimmunity.
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Cites
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Predicting and Manipulating Cardiac Drug Inactivation by the Human Gut Bacterium Eggerthella lenta
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Cited by
Kawano, Y., Edwards, M., Huang, Y., Bilate, A. M., Araujo, L. P., Tanoue, T., Atarashi, K., Ladinsky, M. S., Reiner, S. L., Wang, H. H., et al. (2022) · Cell · doi:10.1016/j.cell.2022.08.005 · Cited by 349
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Modulation of bone remodeling by the gut microbiota: A new therapy for osteoporosis
Lyu, Z., Hu, Y., Guo, Y., & Liu, D. (2023) · Bone Research · doi:10.1038/s41413-023-00264-x · Cited by 207
Molecular basis of bile acid-FXR-FGF15/19 signaling axis
Katafuchi, T., & Makishima, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116046 · Cited by 193
Drummond, R. A., Desai, J. V., Ricotta, E. E., Swamydas, M., Deming, C., Conlan, S., Quinones, M., Matei-Rascu, V., Sheriff, L., Lecky, D., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.04.013 · Cited by 141
Metadata
- Authors
- Alexander, M., Ang, Q. Y., Nayak, R. R., Bustion, A. E., Sandy, M., Zhang, B., Upadhyay, V., Pollard, K. S., Lynch, S. V., & Turnbaugh, P. J.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 30
- Issue
- 1
- Pages
- 17-30.e9
- ISSN
- 1931-3128 (ISSN-L)
- OpenAlex
- W3215646557
- Cited by
- 260
- References
- 13
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
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