Decoding a Gut Commensal Signal: Structural and Immunological Profiling of <i>Segatella Copri</i> Lipopolysaccharide
Abstract
Abstract The immunological effects of lipopolysaccharides (LPSs) from gut microbiota remain poorly explored, overshadowed by the longstanding view of LPS as a prototypical pro‐inflammatory molecule. Herein, we report the first comprehensive chemical and immunological characterization of LPS from Segatella copri DSM 18205, a prominent member of the human oral and intestinal microbiota. This LPS features a unique chemical architecture, including a mannose‐ and glucose‐rich oligosaccharide (OS) and a highly heterogeneous, hypo‐acylated lipid A domain, as elucidated by advanced mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Functionally, S. copri LPS displayed attenuated TLR4 activation and weak pro‐inflammatory activity. Strikingly, high‐dimensional cytometry by time‐of‐flight (CyTOF) revealed a selective preservation of CD14 + CD16 + monocytes, immune subsets typically depleted by canonical enterobacterial LPSs. These findings identify S. copri LPS as a chemically and functionally distinct microbial signature, offering new insights into host‐microbiota immune crosstalk and highlighting its potential for microbiome‐informed immunomodulatory strategies.
Article Details
Authors (18)
Luca De Simone Carone
Department of Chemical Sciences University of Naples Federico II via Cinthia, 4 Naples 80126 Italy
Giusi Barra
Bio‐Organic Chemistry Unit Institute of Biomolecular Chemistry CNR Via Campi Flegrei 34 Naples 80078 Italy
Roberta Cirella
Department of Chemical Sciences University of Naples Federico II via Cinthia, 4 Naples 80126 Italy
Marcello Ziaco
Marcello Mercogliano
Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)
Francesca Olmeo
Department of Chemical Sciences University of Naples Federico II Via Cintia 4 Napoli 80126 Italy
Emanuela Andretta
Department of Chemical Sciences University of Naples Federico II Via Cintia 4 Napoli 80126 Italy
Valentina Mazziotti
Department of Chemical Sciences University of Naples Federico II via Cinthia, 4 Naples 80126 Italy
Carmela Fusco
Bio‐Organic Chemistry Unit Institute of Biomolecular Chemistry CNR Via Campi Flegrei 34 Naples 80078 Italy
Giuliana D'Ippolito
Bio‐Organic Chemistry Unit Institute of Biomolecular Chemistry CNR Via Campi Flegrei 34 Naples 80078 Italy
Katarzyna Anna Duda
Research Center Borstel Leibniz Lung Center 23845 Borstel Germany
Freda M. Farquharson
The Rowett Institute University of Aberdeen Foresterhill Aberdeen AB25 2ZD UK
Petra Louis
The Rowett Institute University of Aberdeen Foresterhill Aberdeen AB25 2ZD UK
Angelo Fontana
Alba Silipo
Dipartimento di Scienze Chimiche, Università degli Studi di Napoli Federico II
Antonio Molinaro
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital
Fabrizio Chiodo
Flaviana Di Lorenzo
Department of Chemical Sciences University of Naples Federico II Via Cintia 4 Napoli 80126 Italy