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Yet, the direct impact of sweeteners on gut bacteria remains largely uncharacterized. Here, we report interactions between 25 phylogenetically diverse gut bacterial strains and 39 commercially used sweeteners. We tested these sweeteners individually and in combination with four commonly co-consumed compounds, viz., advantame, caffeine, vanillin, and duloxetine. Three-quarters of the tested sweeteners individually impacted the growth of at least one tested bacterial strain. Further, over 100 interactions were found between sweeteners and the four co-consumed compounds. Isosteviol, a commonly used sweetener-component, and duloxetine, an antidepressant, synergistically inhibited\n                    <jats:italic>Roseburia intestinalis<\/jats:italic>\n                    , a bacterium previously linked to glucose homeostasis, and\n                    <jats:italic>Parabacteroides merdae<\/jats:italic>\n                    , a prevalent commensal linked to healthy microbiota. Proteomic, metabolomic, and genetic analyses indicate altered small molecule transport underpinning this sweetener\u2013drug synergy. The isosteviol-duloxetine combination also modulated metabolism of a synthetic gut bacterial community, leading to increased toxicity to HeLa cells and altered secretion of inflammation-modulatory cytokines IL-6 and IL-8 by Caco-2 cells. Our data warrant further studies on interactions between low-calorie sweeteners and common xenobiotics.\n                  <\/jats:p>","DOI":"10.1038\/s44320-026-00225-6","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T16:34:13Z","timestamp":1782405253000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Common xenobiotics modulate gut microbial responses to low\u2011calorie sweeteners in vitro"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9422-0474","authenticated-orcid":false,"given":"Sonja","family":"Blasche","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3583-0413","authenticated-orcid":false,"given":"Vinita","family":"Periwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nonantzin","family":"Beristain Covarrubias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4734-5287","authenticated-orcid":false,"given":"Anna","family":"Lindell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7107-2824","authenticated-orcid":false,"given":"Indra","family":"Roux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kamrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0950-8674","authenticated-orcid":false,"given":"Simone","family":"Mozzachiodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7781-9503","authenticated-orcid":false,"given":"Rob","family":"Bradley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilal","family":"Ozgur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bini","family":"Ramachandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0352-2547","authenticated-orcid":false,"given":"Vladimir","family":"Benes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6166-8640","authenticated-orcid":false,"given":"Kiran Raosaheb","family":"Patil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"225_CR1","doi-asserted-by":"publisher","unstructured":"Aliyu M, Zohora FT, Anka AU, Ali K, Maleknia S, Saffarioun M, Azizi G (2022) Interleukin-6 cytokine: an overview of the immune regulation, immune dysregulation, and therapeutic approach. 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