The University of Toledo Translation Journal of Medical Sciences Gastroenterology Abstract, Department of Medicine Research Symposium UTJMS 2023 May 05; 11(1):e1-e2 Cyanotoxin Degrading Lake Bacteria Significantly Alleviate Microcystin-LR Induced Hepatotoxicity in Both In Vitro and In Vivo Models Apurva Lad, PhD1*, Jyotshana Gautam, PhD1, Andrew L. Kleinhenz, BS1, Sanduni H. Premathilaka, MS1, Prabhatchandra Dube, PhD1, Shungang Zhang, PhD1, Travis Stevens, MS1, Dragan Isailovic, PhD1, Jason F. Huntley, PhD2, David J. Kennedy, PhD1; Steven T. Haller, PhD1 1Division of Cardiovascular Medicine, Department of Medicine, The University of Toledo, Toledo, OH 43614 2Department of Medical Microbiology and Immunology, The University of Toledo, Toledo, OH 43614 *Corresponding author: Apurva.Lad@rockets.utoledo.edu Published: 05 May 2023 Introduction: Harmful algal blooms are a potential threat to human health due to the release of cyanotoxins. Our recent reports have shown that exposure to the prevalent cyanotoxin microcystin-LR (MC-LR) exacerbates development of pre-existing liver disease as well as alters gut microbiota that may significantly impact development of hepatotoxicity. We have isolated naturally occurring novel MC-LR degrading bacteria from Lake Erie, OH and hypothesize that they may alleviate MC-LR toxicity. Methods: Human Hep3B hepatocytes were treated with various ratios of hepatocyte:bacterial cells – 1:10, 1:50 and 1:100 for 30 min. prior to exposure with 10 μM MC-LR. After 24 hrs, cells and supernatants were collected for qPCR and mass spectrometric analysis. Age-matched Balb/c female mice were either given normal or a mix of MC-degrading bacteria (105 CFU/ml) in drinking water for four weeks followed by a single gavage with vehicle or 500 μg/kg of MC-LR and then euthanized 2 or 24 hrs post-exposure. Urine and organs were collected for qPCR and mass spectrometric analysis. Results: Genetic analysis for markers of hepatotoxicity and inflammation in both in vivo and in vitro settings were significantly downregulated in the presence of MC-degrading bacteria compared to the untreated groups. Mass spectrometric analysis of urine from mice pre-treated with the bacteria prior to MC-LR exposure, revealed significant reduction in urine MC-LR levels and elevated levels of the detoxified metabolite - MC-LR Cysteine as compared to the untreated control group. https://dx.doi.org/10.46570/utjms.vol11-2023-655 https://dx.doi.org/10.46570/utjms.vol11-2023-655 mailto:Apurva.Lad@rockets.utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-655 UTJMS 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-655 2 ©2023 UTJMS Conclusion: These results suggest a potential novel therapeutic approach that can be developed for MC- LR induced toxicity. https://dx.doi.org/10.46570/utjms.vol11-2023-655 https://dx.doi.org/10.46570/utjms.vol11-2023-655