| Autor: |
Older, Ethan A., Zhang, Jian, Ferris, Zachary E., Xue, Dan, Zhong, Zheng, Mitchell, Mary K., Madden, Michael, Wang, Yuzhen, Chen, Hexin, Nagarkatti, Prakash, Nagarkatti, Mitzi, Fan, Daping, Ellermann, Melissa, Li, Yong-Xin, Li, Jie |
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| Zdroj: |
Nature Communications; 10/30/2024, Vol. 15 Issue 1, p1-17, 17p |
| Abstrakt: |
The trillions of microorganisms inhabiting the human gut are intricately linked to human health. While specific microbes have been associated with diseases, microbial abundance alone cannot reveal the molecular mechanisms involved. One such important mechanism is the biosynthesis of functional metabolites. Here, we develop a biosynthetic enzyme-guided disease correlation approach to uncover microbial functional metabolites linked to disease. Applying this approach, we negatively correlate the expression of gut microbial sulfonolipid (SoL) biosynthetic enzymes to inflammatory bowel disease (IBD). Targeted chemoinformatics and metabolomics then confirm that SoL abundance is significantly decreased in IBD patient data and samples. In a mouse model of IBD, we further validate that SoL abundance is decreased while inflammation is increased in diseased mice. We show that SoLs consistently contribute to the immunoregulatory activity of different SoL-producing human microbes. We further reveal that sulfobacins A and B, representative SoLs, act on Toll-like receptor 4 (TLR4) and block lipopolysaccharide (LPS) binding, suppressing both LPS-induced inflammation and macrophage M1 polarization. Together, these results suggest that SoLs mediate a protective effect against IBD through TLR4 signaling and showcase a widely applicable biosynthetic enzyme-guided disease correlation approach to directly link the biosynthesis of gut microbial functional metabolites to human health. Human microbes biosynthesize functional metabolites to influence human health. Here, the authors link the biosynthesis of microbial sulfonolipids (SoLs) to inflammatory bowel diseases, and reveal that SoLs block LPS binding to TLR4, suppressing LPS-induced inflammation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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