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Here, we examined the strain-specific transcriptomic and metabolic responses of\n                      <jats:italic toggle=\"yes\">Clostridium butyricum<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Bacteroides thetaiotaomicron<\/jats:italic>\n                      grown in pure anaerobic culture with 0.1% (wt\/vol) MSG. Although MSG exposure was not associated with major changes in total bacterial biomass dynamics, both species showed a temporal functional reprogramming. In\n                      <jats:italic toggle=\"yes\">C. butyricum<\/jats:italic>\n                      , MSG rapidly intensified metabolic activity to capitalize on exogenous glutamate by activating central carbon metabolism, redox-balancing pathways, and the GABA shunt, thereby collectively enhancing butyrate synthesis, a metabolite associated with gut barrier integrity, energy regulation, and anti-inflammatory signaling. On the other hand,\n                      <jats:italic toggle=\"yes\">B. thetaiotaomicron<\/jats:italic>\n                      adopted a conservative, homeostatic response, suppressing glycan utilization and central carbon and energy metabolism, and maintaining stable SCFA production through controlled regulation that buffered against abrupt dietary perturbations. Overall, MSG functioned as a potent metabolic signal, triggering distinct adaptive strategies in two dominant gut bacteria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>The impact of monosodium glutamate (MSG) as a highly consumed food additive on the gut microbiome is often overlooked, and community-level analyses reveal little change, masking distinct phenotypic responses of individual strains. By combining gene expression and metabolite profiling using two key human gut bacteria, we show that MSG is sensed as a metabolic signal. A butyrate-producing gut bacterium increases energy metabolism and butyrate production, and a fiber-degrading gut bacterium transiently moderates metabolism to maintain stable fermentation products. These differences suggest that MSG's physiological effects may depend on which bacterial groups dominate an individual\u2019s microbiome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00190-26","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:01:01Z","timestamp":1786366861000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>In vitro<\/i>\n                    metabolic signaling in two intestinal bacterial isolates: glutamate-driven transcriptional and functional reprogramming in\n                    <i>Clostridium butyricum<\/i>\n                    and\n                    <i>Bacteroides thetaiotaomicron<\/i>"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3309-066X","authenticated-orcid":true,"given":"Nazanin","family":"Nematzadeh Somehsaraei","sequence":"first","affiliation":[{"name":"ZIEL-Institute 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