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Secondary Bile Acids Modified by Odoribacter Splanchnicus Alleviate Colitis by Suppressing Neutrophil Extracellular
Jing Xu1,2, Jianhong Li1,2, Xue Guo1,2
1Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
Odoribacter splanchnicus, depleted in inflammatory bowel disease (IBD), protects against colitis in mice. It reduces inflammation by increasing lithocholic acid (LCA), which inhibits neutrophil extracellular traps (NETs) formation.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- The gut microbiota's role in inflammatory bowel disease (IBD) is significant, but the specific functions of bacterial species are not fully understood.
- Identifying key bacterial taxa and their mechanisms in IBD pathogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the protective role of Odoribacter splanchnicus (O. splanchnicus) in inflammatory bowel disease (IBD) models.
- To elucidate the mechanisms by which O. splanchnicus exerts its anti-inflammatory effects, focusing on neutrophil extracellular traps (NETs) and bile acid metabolism.
Main Methods:
- O. splanchnicus administration in acute and chronic murine colitis models.
- Assessment of colonic inflammation, barrier integrity, mucosal immune landscape, and NETs formation.
- Metabolomic profiling to identify key metabolites, including bile acids.
- Supplementation studies with lithocholic acid (LCA) and fecal microbiota transplantation (FMT).
- Investigation of the NLRP3-GSDMD signaling pathway.
Main Results:
- O. splanchnicus administration significantly alleviated colonic inflammation and improved barrier integrity in mice.
- O. splanchnicus treatment reduced NETs formation, dependent on the host's NETs machinery (Pad4).
- Treatment increased levels of the secondary bile acid lithocholic acid (LCA) in a microbiota-dependent manner.
- LCA supplementation mimicked the anti-NETs effect and suppressed inflammation by inhibiting the NLRP3-GSDMD pathway.
Conclusions:
- Odoribacter splanchnicus possesses protective effects against colitis, mediated by the microbiota-dependent production of LCA.
- LCA suppresses colonic inflammation by inhibiting NETs formation via the NLRP3-GSDMD pathway.
- These findings establish a gut microbiota-metabolite-neutrophil axis critical in IBD pathogenesis and highlight LCA as a key protective factor.
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