The Li lab’s recent publication combines informatic, computational, and biochemical studies to elucidate the protective effect of gut microbial lipids against inflammatory bowel disease.

 

Researchers from the Department of Chemistry and Biochemistry are one step closer to elucidating the molecular connections between the bacteria living in us and our gut health. These microbes, collectively known as the human microbiota, produce numerous metabolites that have constant interactions with human cells. They can influence a variety of pathways, including inflammation or cancer, but connecting these metabolites to diseases remains a difficult task. The integration of multiple fields is required to generate a comprehensive view of these interactions.

In a recent article published in Nature Communications, the Li lab and their collaborator used a combination of informatics, immunology, and biochemistry to show how one such class of bacterial molecules – termed sulfonolipids (SoLs) – could help against gut inflammation. Data from The Inflammatory Bowel Disease Multi'omics Database (IBDMD) negatively correlated the expression of SoLs-synthesizing enzymes with IBD occurrence. Likewise, cells treated with SoLs showed a marked reduction in inflammation in response to lipopolysaccharide (LPS), a potent bacterial toxin. Molecular docking and biochemical studies then revealed that SoLs can displace LPS bound to Toll-like Receptor 4 (TLR4), suppressing downstream pro-inflammatory signaling. These results suggest that SoLs may interfere with LPS signaling to protect against inflammatory diseases.

The combination of approaches used in this study represents a novel, hypothesis-driven method to connect specific metabolites to disease. With the increasing availability of sequencing data and continuous advancements in our understanding of biosynthetic pathways, this workflow can be used to target other microbial metabolites for investigation.