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Among cyanotoxins, microcystin-LR (MC-LR) is one of the most prevalent variants and is recognized for its hepatotoxicity, with evidence showing it can also alter gut microbiota composition. Previous studies, including our own, demonstrate that MC exposure can induce inflammation, oxidative stress, and changes in gene expression associated with immune responses, even at concentrations below guideline limits. This study investigated the protective effect of an MC-degrading bacterium, Sphingopyxis sp. IM1 (IM1) with a known enzymatic MC degradation pathway, against MC-LR-induced hepatotoxicity under in vitro conditions. Human Hep3B hepatocytes were pretreated with varying ratios of IM1 bacteria and subsequently exposed to 9.95 ppm of MC-LR for 24 h. RT-qPCR analysis demonstrated that MC-LR exposure strongly increased the expression of the inflammatory markers TNF\u03b1 and TGF-\u03b21, whereas pretreatment with IM1 significantly attenuated these responses. Mass spectrometric analysis of cell pellets and spent culture media demonstrated reduced concentrations of intact MC-LR in IM1-pretreated samples compared to MC-LR-only controls, accompanied by increased detection of tetrapeptide degradation products generated during mlr-mediated MC degradation. These results demonstrate that IM1-mediated degradation of MC-LR attenuates toxin-induced hepatotoxic and inflammatory responses, highlighting the potential of a novel microbial-based therapeutic approach to mitigate MC-induced toxicity.<\/jats:p>","DOI":"10.3390\/toxins18080337","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T08:04:59Z","timestamp":1785744299000},"page":"337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sphingopyxis sp. IM-1 Reduces Intact Microcystin-LR and Attenuates MC-LR-Associated Inflammatory Gene Expression in Hep3B Hepatocytes"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6073-7432","authenticated-orcid":false,"given":"Apurva","family":"Lad","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Toledo, Mail Stop 1040, Health Education Building, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-6625","authenticated-orcid":false,"given":"Mudit","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Civil and Environmental Engineering, University of Toledo, Mail Stop 307, 3006 Nitschke Hall, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnna A.","family":"Birbeck","sequence":"additional","affiliation":[{"name":"Lumigen Instrument Center, Department of Chemistry, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Kuang","sequence":"additional","affiliation":[{"name":"Lumigen Instrument Center, Department of Chemistry, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Furr","sequence":"additional","affiliation":[{"name":"Lumigen Instrument Center, Department of Chemistry, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Westrick","sequence":"additional","affiliation":[{"name":"Lumigen Instrument Center, Department of Chemistry, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngwoo","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Civil and Environmental Engineering, University of Toledo, Mail Stop 307, 3006 Nitschke Hall, Toledo, OH 43606, USA"},{"name":"Department of Chemical Engineering, University of Toledo, Mail Stop 307, 3048 Nitschke Hall, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2585-1974","authenticated-orcid":false,"given":"Dae-Wook","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Civil and Environmental Engineering, University of Toledo, Mail Stop 307, 3006 Nitschke Hall, Toledo, OH 43606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5265-0142","authenticated-orcid":false,"given":"David J.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo, Mail Stop 1040, Health Education Building, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6919-6342","authenticated-orcid":false,"given":"Steven T.","family":"Haller","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo, Mail Stop 1040, Health Education Building, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1002\/lno.11120","article-title":"Deciphering the Effects of Nitrogen, Phosphorus, and Temperature on Cyanobacterial Bloom Intensification, Diversity, and Toxicity in Western Lake Erie","volume":"64","author":"Jankowiak","year":"2019","journal-title":"Limnol. 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