Luca De Simone Carone,Giusi Barra,Roberta Cirella,Marcello Ziaco,Marcello Mercogliano,Francesca Olmeo,Emanuela Andretta,Valentina Mazziotti,Carmela Fusco,Giuliana D'Ippolito,Katarzyna Anna Duda,Freda M Farquharson,Petra Louis,Angelo Fontana,Alba Silipo,Antonio Molinaro,Fabrizio Chiodo,Flaviana Di Lorenzo
{"title":"Decoding a Gut Commensal Signal: Structural and Immunological Profiling of Segatella Copri Lipopolysaccharide.","authors":"Luca De Simone Carone,Giusi Barra,Roberta Cirella,Marcello Ziaco,Marcello Mercogliano,Francesca Olmeo,Emanuela Andretta,Valentina Mazziotti,Carmela Fusco,Giuliana D'Ippolito,Katarzyna Anna Duda,Freda M Farquharson,Petra Louis,Angelo Fontana,Alba Silipo,Antonio Molinaro,Fabrizio Chiodo,Flaviana Di Lorenzo","doi":"10.1002/anie.202512947","DOIUrl":null,"url":null,"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.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"100 1","pages":"e202512947"},"PeriodicalIF":16.9000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Angewandte Chemie International Edition","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1002/anie.202512947","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.