{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:28:19Z","timestamp":1786429699329,"version":"build-2736575974"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The immunomodulatory effects of gut\n                      <jats:italic>Bacteroides<\/jats:italic>\n                      are typically attributed to surface polysaccharides signaling through TLR2 and TLR4, and to outer membrane vesicles (OMVs) that traffic effector molecules to host cells. However, these bacteria also secrete a wide array of metabolites, including short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), phenolic compounds, and aldehydes, whose contributions to immune modulation remain underexplored. Moreover, it is unclear whether different\n                      <jats:italic>Bacteroides<\/jats:italic>\n                      and\n                      <jats:italic>Phocaeicola<\/jats:italic>\n                      species share similar immunomodulatory profiles or display species- and strain-specific activities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We cultivated 18 strains of\n                      <jats:italic>Bacteroides<\/jats:italic>\n                      and\n                      <jats:italic>Phocaeicola<\/jats:italic>\n                      , collected their conditioned media, and applied them to HT-29 intestinal epithelial cells.\n                      <jats:italic>TLR2<\/jats:italic>\n                      and\n                      <jats:italic>TLR4<\/jats:italic>\n                      gene expression and IL-8 secretion were measured under basal and LPS-stimulated conditions. The volatile metabolome was characterized using HS-GC\/MS, and the data were integrated with cellular responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The strains induced strikingly divergent effects, ranging from strong suppression to marked induction of\n                      <jats:italic>TLR2\/TLR4<\/jats:italic>\n                      expression and IL-8 production. Metabolomic profiling revealed that while SCFAs and MCFAs were associated with anti-inflammatory outcomes, the presence of phenolic compounds and aldehydes correlated with pro-inflammatory effects. Integration of metabolomic and cellular data allowed us to classify the strains into three functional categories: anti-inflammatory (e.g.,\n                      <jats:italic>B. uniformis<\/jats:italic>\n                      EBA 5-20), pro-inflammatory (e.g.,\n                      <jats:italic>B. thetaiotaomicron<\/jats:italic>\n                      6-237), and strains with context-dependent mixed effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The immunomodulatory activity of gut\n                      <jats:italic>Bacteroides and Phocaeicola<\/jats:italic>\n                      cannot be predicted solely by their taxonomic affiliation; rather, it depends on the specific repertoire of secreted metabolites and their interplay with host pathways. Evaluating both metabolomic profiles and receptor-mediated responses provides a rational basis for selecting candidate probiotics for personalized microbiome modulation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1897419","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:39:55Z","timestamp":1786426795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual immunomodulatory effects of bacteroides and phocaeicola secretomes revealed by integrative metabolomic and functional screening in HT-29 cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Irina V.","family":"Podoprigora","sequence":"first","affiliation":[{"name":"Department of Microbiology named after V.S. Kiktenko, Peoples\u2019 Friendship University of Russia named after Patrice Lumumba (RUDN University)","place":["Moscow, Russia"]},{"name":"Department of Microbiology and Virology, Institute of Preventive Medicine named after Z.P. Solovyov, Pirogov Russian National Research Medical University","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya B.","family":"Zakharzhevskaya","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milana S.","family":"Das","sequence":"additional","affiliation":[{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia Named after Patrice Lumumba (RUDN University)","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei V.","family":"Chaplin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Virology, Institute of Preventive Medicine named after Z.P. Solovyov, Pirogov Russian National Research Medical University","place":["Moscow, Russia"]},{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry A.","family":"Kardonsky","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta A.","family":"Vorobyeva","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria A.","family":"Kashatnikova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]},{"name":"The Laboratory of Ecological Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoriia D.","family":"Kazakova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina V.","family":"Kolesnikova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana V.","family":"Smirnova","sequence":"additional","affiliation":[{"name":"The Laboratory of Ecological Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana N.","family":"Kalachnuk","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razan","family":"Marouf","sequence":"additional","affiliation":[{"name":"Department of Microbiology named after V.S. Kiktenko, Peoples\u2019 Friendship University of Russia named after Patrice Lumumba (RUDN University)","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris A.","family":"Efimov","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Virology, Institute of Preventive Medicine named after Z.P. Solovyov, Pirogov Russian National Research Medical University","place":["Moscow, Russia"]},{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.aninu.2021.11.005","article-title":"Gut microbiota-derived short chain fatty acids are potential mediators in gut inflammation","volume":"8","author":"Akhtar","year":"2022","journal-title":"Anim. 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