{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:13:34Z","timestamp":1790745214464,"version":"4.1.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>\n                    Lipopolysaccharides (LPSs) from Gram-negative bacteria are widely used to model neuroinflammation\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . However, this paradigm assumes that all LPS chemotypes are uniformly pro-inflammatory, despite significant structural diversity between enterobacterial pathogens and gut-resident commensals. Whether microglia can discriminate among these chemotypes remains largely unexplored. We performed a comparative analysis of canonical\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    LPS and commensal-derived\n                    <jats:italic>Phocaeicola vulgatus<\/jats:italic>\n                    LPS in murine (BV2) and human (HMC3) microglial cells. Pro-inflammatory mediators were quantified by ELISA, and TLR4-downstream signaling was assessed by western blotting. Conditioned media (CM) from LPS-treated BV2 and HMC3 cells was applied to PC12 neuronal cells to evaluate cell viability and differentiation by immunofluorescence. In BV2 microglial cells,\n                    <jats:italic>P. vulgatus<\/jats:italic>\n                    LPS did not induce nitric oxide (NO) production or iNOS expression. In both BV2 and HMC3 cells, it failed to trigger pro-inflammatory cytokine release or TLR4 pathway activation. CM from\n                    <jats:italic>E. coli<\/jats:italic>\n                    -treated microglia disrupted MAP2 expression in PC12 neurons, whereas media from\n                    <jats:italic>P. vulgatus<\/jats:italic>\n                    -treated microglia did not. Overall, our data argue that \u201cLPS-induced neuroinflammation\u201d is not a universal phenomenon, but a chemistry-dependent outcome shaped by specific LPS structures. This study therefore highlights the need to consider LPS structural diversity in neuroinflammation models, particularly in the context of gut-brain communication.\n                  <\/jats:p>","DOI":"10.3389\/fncel.2026.1796397","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:20:55Z","timestamp":1776140455000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Structure matters: commensal Phocaeicola vulgatus lipopolysaccharide induces attenuated microglial activation and preserves neuronal integrity"],"prefix":"10.3389","volume":"20","author":[{"given":"Valentina","family":"Mazziotti","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II","place":["Naples, Italy"]},{"name":"CEINGE-Biotecnologie Avanzate Franco Salvatore","place":["Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"De Simone Carone","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II","place":["Naples, Italy"]},{"name":"CEINGE-Biotecnologie Avanzate Franco Salvatore","place":["Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Olmeo","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II","place":["Naples, Italy"]},{"name":"CEINGE-Biotecnologie Avanzate Franco Salvatore","place":["Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Chiodo","sequence":"additional","affiliation":[{"name":"Bio-Organic Chemistry Unit, Institute of Biomolecular Chemistry CNR","place":["Naples, Italy"]},{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Silipo","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II","place":["Naples, Italy"]},{"name":"CEINGE-Biotecnologie Avanzate Franco Salvatore","place":["Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Molinaro","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II","place":["Naples, Italy"]},{"name":"CEINGE-Biotecnologie Avanzate Franco Salvatore","place":["Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaviana","family":"Di Lorenzo","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II","place":["Naples, Italy"]},{"name":"CEINGE-Biotecnologie Avanzate Franco Salvatore","place":["Naples, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12974-025-03360-3","article-title":"Innate immune sensors and regulators at the blood brain barrier: focus on toll-like receptors and inflammasomes as mediators of neuro-immune crosstalk and inflammation.","volume":"22","author":"Acioglu","year":"2025","journal-title":"J. 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