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Decoding a Gut Commensal Signal: Structural and Immunological Profiling of Segatella Copri Lipopolysaccharide
Luca De Simone Carone1,2,3, Giusi Barra4, Roberta Cirella1
1Department of Chemical Sciences, University of Naples Federico II, via Cinthia, 4, Naples, 80126, Italy.
Angewandte Chemie (International Ed. in English)
|September 30, 2025
Summary
Lipopolysaccharides (LPSs) from gut bacteria like Segatella copri have unique structures and trigger weaker immune responses than previously thought. This discovery offers new avenues for microbiome-based immune therapies.
Area of Science:
- Immunology
- Microbiology
- Chemical Biology
Background:
- Lipopolysaccharides (LPSs) from gut microbiota are poorly understood, often viewed solely as pro-inflammatory molecules.
- The immune effects of LPSs from specific gut bacteria require further investigation.
Purpose of the Study:
- To conduct a comprehensive chemical and immunological characterization of LPS from Segatella copri DSM 18205.
- To explore the distinct immune signaling properties of S. copri LPS.
Main Methods:
- Advanced mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy for chemical structure elucidation.
- Functional assays assessing Toll-like receptor 4 (TLR4) activation and pro-inflammatory cytokine production.
- High-dimensional cytometry by time-of-flight (CyTOF) to analyze immune cell subset responses.
Main Results:
- S. copri LPS possesses a unique chemical structure with a mannose- and glucose-rich oligosaccharide and a hypo-acylated lipid A.
- This LPS demonstrated attenuated TLR4 activation and weak pro-inflammatory activity.
- S. copri LPS selectively preserved CD14+CD16+ monocytes, unlike typical enterobacterial LPSs.
Conclusions:
- Segatella copri LPS is a chemically and functionally distinct microbial signature.
- These findings provide novel insights into host-microbiota immune interactions.
- S. copri LPS holds potential for developing microbiome-informed immunomodulatory strategies.
