Cyanotoxin Degrading Lake Bacteria Significantly Alleviate Microcystin-LR Induced Hepatotoxicity in Both In Vitro and In Vivo Models

Our recent reports have shown that exposure to microcystin-LR (MC-LR) exacerbates the development of pre-existing liver and inflammatory bowel 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 hypothesized that they may alleviate MC-LR toxicity. qPCR analysis for markers of hepatotoxicity and inflammation in both in vivo and in vitro (using human Hep3B hepatocytes) settings showed significant downregulation in their expression in presence of MC degrading bacteria compared to the untreated groups. LC-MS analysis of the 24-hour urine samples in an in vivo setting with age matched Balb/c female mice that were pre-treated with the bacteria prior to 500 μg/kg MC-LR exposure for 24 hrs revealed significant reduction in urine MC-LR levels of mice pre-treated with MC-LR degrading bacteria as compared to the control group. Analysis of genes related to MC-LR induced apoptosis, DNA damage, ER stress, and fatty acid metabolism were also significantly downregulated in mice treated with MC degrading bacteria compared to control mice exposed to the toxin alone. These results suggest a potential novel therapeutic approach that can be developed for MC-LR induced toxicity

Aerosolized microcystin-LR exacerbates chemokines and other inflammatory mediators of asthma in asthmatic primary human airway epithelium

Microcystin-LR, one of the most abundant and toxic HAB-derived cyanotoxins, has recently been detected in aerosols from HAB water. We previously reported that aerosol MC-LR exposure has a pro-inflammatory influence on the airways. Asthma, which is an extremely prevalent airway disease afflicting approximately 8% of the U.S. population, is largely driven by inflammation. However, the impact of MC-LR aerosol exposure on this at-risk population is unknown. In this study, a 3D primary human airway epithelium model was utilized, in which cells were isolated from healthy and asthmatic donors. An environmentally relevant concentration of MC-LR (1 μM) was aerosolized and delivered to the cell surface, before the cells were harvested for transcriptome analysis. Strikingly, 10% of the genes upregulated (log2FC \u3e 0.25) by asthma alone, were further upregulated by MC-LR exposure including inflammation mediators, such as CXCL11 (log2FC = 0.63); and TLR4 (log2FC = 0.31). These genes had significant associations with pathways, such as “immune cytokine binding” (FDR = 0.015). This study showed that aerosolized MC-LR amplifies the transcriptional differences between asthmatic and healthy donor airway epithelial cells, leading to the exacerbation of inflammatory mediators of asthma, such as chemokines, suggesting a potential for MC-LR exposure to worsen asthma severity