{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:08:15Z","timestamp":1775538495075,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"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":"\n Introduction<\/jats:title>\n \n Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, is linked to cardiovascular, neurodegenerative, and metabolic diseases. Emerging evidence indicates a bidirectional interaction between the periodontal pathogen\n Porphyromonas gingivalis<\/jats:italic>\n (\n Pg<\/jats:italic>\n ) and gut microbiota, potentially influencing host TMAO metabolism. However, whether\n Pg<\/jats:italic>\n modulates the choline-trimethylamine (TMA) axis remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Wild-type male C57BL\/6J mice received oral\n Pg<\/jats:italic>\n under chow or a high-choline diet. Plasma and cecal concentrations of TMA and TMAO were quantified, intestinal barrier function was evaluated via histological analysis, and the determination of ZO-1 and occludin expression was performed. Cecal microbiota composition was profiled by 16S rRNA gene sequencing, and microbial choline-TMA lyase markers (\n cutC<\/jats:italic>\n \/\n cutD<\/jats:italic>\n ) were measured.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Pg<\/jats:italic>\n elevated plasma TMAO under chow, accompanied by reduced\n \u03b1<\/jats:italic>\n -diversity, altered\n \u03b2<\/jats:italic>\n -diversity, and decreased expression of intestinal barrier proteins. Under high-choline conditions, the diet itself increased plasma and intestinal levels of TMAO and TMA.\n Pg<\/jats:italic>\n co-exposure further amplified these effects, raising plasma TMAO, cecal TMA, and\n cutC<\/jats:italic>\n \/\n cutD<\/jats:italic>\n levels. Microbiome analysis revealed elevated abundances of\n Lachnoclostridium<\/jats:italic>\n ,\n Odoribacter<\/jats:italic>\n , and\n Colidextribacter<\/jats:italic>\n , and reduced levels of taxa (\n Prevotellaceae NK3B31<\/jats:italic>\n ,\n Anaerostipes<\/jats:italic>\n , and\n Ruminococcus<\/jats:italic>\n ) negatively correlated with TMAO-related parameters. Moreover,\n cutC<\/jats:italic>\n \/\n cutD<\/jats:italic>\n levels were positively correlated with\n Colidextribacter<\/jats:italic>\n and\n Lachnoclostridium<\/jats:italic>\n , but negatively correlated with\n Anaerostipes<\/jats:italic>\n and\n Prevotellaceae NK3B31<\/jats:italic>\n , consistent with the modulation of TMA\/TMAO metabolism by these taxa.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This study demonstrates that oral administration of\n Pg<\/jats:italic>\n facilitates systemic TMAO elevation by reshaping gut microbial communities and enhancing choline-TMA lyase function, and compromising intestinal barrier integrity. These findings establish an oral-gut metabolic axis connecting periodontitis to host TMAO metabolism, and highlight promising periodontal and microbiota-targeted strategies for alleviating TMAO-associated systemic disorders.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1786725","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T04:25:26Z","timestamp":1775535926000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Porphyromonas gingivalis drives trimethylamine-N-oxide accumulation via modulation of gut microbial trimethylamine lyase in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Weige","family":"Xie","sequence":"first","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Han","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinlu","family":"Tan","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingwen","family":"Dong","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Wu","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuebin","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Oral Biology, School of Dentistry, University of Leeds","place":["Leeds, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijing","family":"Xie","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"100633","DOI":"10.1016\/j.ahjo.2025.100633","article-title":"Gut microbiome dysbiosis in heart failure: updated evidence, mechanisms, and therapeutic directions","volume":"59","author":"Albulushi","year":"2025","journal-title":"Am Heart J Plus."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"7045","DOI":"10.3390\/molecules26227045","article-title":"Adaptive modelling of mutated FMO3 enzyme could unveil unexplored scenarios linking variant haplotypes to TMAU phenotypes","volume":"26","author":"Alibrandi","year":"2021","journal-title":"Molecules"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1637071","DOI":"10.3389\/fnut.2025.1637071","article-title":"Trust your gut: exploring the connection between gut microbiome dysbiosis and the advancement of metabolic associated steatosis liver disease (MASLD)\/metabolic associated Steatohepatitis (MASH): a systematic review of animal and human studies","volume":"12","author":"Bahitham","year":"2025","journal-title":"Front. 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