{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:02:13Z","timestamp":1789182133156,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":97,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study investigated the link between an imbalance in microbiota\u2010derived short\u2010chain fatty acids (SCFAs) and dysregulated host immunity in periodontitis, focusing on the metabolic reprograming of inflammatory macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a systematic review and meta\u2010analysis of SCFA levels. Bulk RNA sequencing (RNA\u2010seq) data from human gingival tissue (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200924) were analyzed for differential expression and pathway enrichment, with immune cell composition estimated by Cell\u2010type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT). Mouse single\u2010cell RNA\u2010seq (scRNA\u2010seq) data were integrated, and myeloid cells (MCs) were subset for detailed clustering, differential analysis, and pseudotime trajectory reconstruction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Meta\u2010analysis indicated a decreasing, though nonsignificant, trend in butyrate levels in periodontitis. Bulk RNA\u2010seq identified 692 differentially expressed genes (DEGs) enriched in immune and cytokine signaling pathways. Immune deconvolution revealed an increased proportion of M1 macrophages and Tregs, alongside a decrease in M2 macrophages. Single\u2010cell analysis confirmed the significant expansion of M1\u2010like macrophages, which highly expressed SCFA receptors (Gpr43 and Gpr109a), inflammatory transcription factors (Nfkb1 and Hif1a), and effector molecules (Il1b). The pseudotime trajectory demonstrated a continuous M2\u2010to\u2010M1 polarization, marked by a decline in M2 markers and a rise in M1 markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Periodontitis is characterized by SCFA metabolic imbalance and a shift in MCs toward a pro\u2010inflammatory M1 state. The upregulation of SCFA receptors and the NF\u2010\u03baB\/HIF\u20101 axis in M1 macrophages suggests an \u201cSCFA receptor\u2013metabolic sensing\u2013inflammatory transcription\u201d mechanism drives disease progression, providing a rationale for therapeutic strategies targeting this pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/3542645","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T09:15:33Z","timestamp":1775639733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Signaling Through SCFA Receptors Gpr43 and Gpr109a Drives Pro\u2010Inflammatory M1 Macrophage Polarization in Periodontitis"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3092-1377","authenticated-orcid":false,"given":"Kun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4113-3179","authenticated-orcid":false,"given":"Ruolin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7137-3149","authenticated-orcid":false,"given":"Lingxue","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2451-7653","authenticated-orcid":false,"given":"Lisi","family":"Ai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2024.08.003"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.13919"},{"key":"e_1_2_13_3_2","first-page":"273","article-title":"Periodontal 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