{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:02:17Z","timestamp":1780038137584,"version":"3.53.1"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Outer membrane vesicles released by Porphyromonas gingivalis (Pg-OMVs) are emerging as critical mediators of periodontal and systemic pathology. Published literature has so far associated the presence of OMVs to an increased risk of cerebrovascular and neurodegenerative diseases, but the molecular-scale mechanisms underlying their interactions with immune cells remain insufficiently understood and characterized. Here, we employ high-resolution Raman spectroscopy in addition to established immunoassays to quantitatively decode the real-time chemical reprogramming induced by Pg-OMVs in macrophages. Our results reveal early and pronounced alterations in lipid composition, including significant increases in sphingomyelin- and ceramide-associated vibrational signatures, paralleled by perturbations in cholesterol-rich membrane domains. These lipidomic changes coincide with Raman markers of mitochondrial dysfunction, as characterized by reduced cytochrome c oxidation signals, indicating a shift toward a more reduced redox state. We further identify time-resolved modifications of glycogen-associated bands, implicating metabolic rewiring and inflammatory activation. Together, these spectral fingerprints demonstrate how Pg-OMVs orchestrate a coordinated disruption of membrane architecture, intracellular lipid homeostasis, and mitochondrial function. Raman findings provide a non-destructive, label-free molecular atlas of OMV-driven macrophage dysregulation and establish Raman spectroscopy as a powerful platform for quantitatively elucidating host\u2013pathogen interactions with direct relevance to oral-systemic health and chronic inflammatory disease.<\/jats:p>","DOI":"10.3389\/fmicb.2026.1803640","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:09:37Z","timestamp":1780034977000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering macrophage molecular responses to Porphyromonas gingivalis outer membrane vesicles through combined immunoassay and Raman spectroscopic analyses"],"prefix":"10.3389","volume":"17","author":[{"given":"Yoshiyuki","family":"Matsuo","sequence":"first","affiliation":[{"name":"Central Research Center, Institute of Biomedical Science, Kansai Medical University","place":["Hirakata, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoi","family":"Son","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Center, Kansai Medical University","place":["Hirakata, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gentile","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Center, Kansai Medical University","place":["Hirakata, Japan"]},{"name":"Department of Chemistry and Technologies of Drugs, Sapienza University of Rome","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Bernola","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Center, Kansai Medical University","place":["Hirakata, Japan"]},{"name":"Department of Chemistry and Technologies of Drugs, Sapienza University of Rome","place":["Rome, 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Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luna","family":"Ardondi","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Center, Kansai Medical University","place":["Hirakata, Japan"]},{"name":"Department of Translational Medicine, University of Ferrara","place":["Ferrara, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kariu","sequence":"additional","affiliation":[{"name":"Department of Food and Fermentation Science, Beppu University","place":["Beppu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Zavan","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara","place":["Ferrara, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Ceramic Physics Laboratory, Kyoto Institute of Technology","place":["Kyoto, 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Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Kamioka","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University","place":["Hirakata, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Secci","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technologies of Drugs, Sapienza University of Rome","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Pinton","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Center, Kansai Medical University","place":["Hirakata, Japan"]},{"name":"Laboratory for Technologies of Advanced Therapies (LTTA), Department of Medical Sciences, University of Ferrara","place":["Ferrara, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pezzotti","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Center, Kansai Medical University","place":["Hirakata, Japan"]},{"name":"Biomarker Disease Laboratory, IRCCS San Camillo Hospital","place":["Venice, Italy"]},{"name":"International Center for Biomedical Industrial Promotion, Kansai Medical University","place":["Osaka, Japan"]},{"name":"Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine","place":["Kyoto, Japan"]},{"name":"Department of Orthopedic Surgery, Tokyo Medical University","place":["Tokyo, Japan"]},{"name":"Department of Molecular Science and Nanosystems, Ca\u2019 Foscari University of Venice","place":["Venice, Italy"]},{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine, Mie University","place":["Tsu, Japan"]},{"name":"Teikyo University Institute of Medical Mycology (TIMM), Graduate 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