Microcystis toxin-mediated tumor promotion and toxicity lead to shifts in mouse gut microbiome

Microcystins (MCs) are the most prevalent cyanotoxins reported in freshwater. While numerous studies have examined the toxicological impacts of MCs on mammalian systems, very few have examined the chronic impacts of MCs on the gut microbiome of exposed organisms. Our understanding of the relationship of MCs, especially lysed toxic cyanobacteria, and the gut microbiota is very limited. The objective of this study was to determine the impacts of MC-LR and Microcystis lysate ingestion on the gut microbiome in a hepatocellular carcinoma mouse model, simulating a high-risk population and exposure at an environmentally relevant MC level. Mice were assigned to 4 groups (MC-LR; Microcystis lysate; Negative control; Positive (liver carcinogen) control). Fecal samples were collected every 8 weeks. Bacterial community and colony counts were analyzed. The abundance of Firmicutes in the positive control and lysate group was higher than the negative control and MC group. Exposure to MC-LR or lysate was associated with significantly decreased bacterial diversity. A distinct separation of the three groups (MC-LR/lysate/carcinogen) from the negative was much more apparent in their gut microbiome as the exposure time increased. The MC-LR and lysate groups showed gut microbiome structure responding to lipid metabolism disturbance and high stress. Bacterial colony count was significantly lower in all the treated groups than the negative control. Our study highlights that chronic exposure to MC-LR and Microcystis lysate negatively impacts gut microbiome succession and altered the bacterial community structure into the one similar to the carcinogen group, which may indicate that the change favors progression of hepatocellular carcinoma. In a future study, more in-depth investigation is warranted to better understand the liver-gut nexus in promoting liver cancer among those exposed to MC and toxic cyanobacteria.