The threat is in the details – critical gap in ecotoxicological assessment of Microcystis blooms revealed by critical distinctions of genotype effects induced on Medaka fish

Microcystis spp., prolific bloom-forming freshwater cyanobacteria, produce a wide range of bioactive secondary metabolites. While microcystins (MCs) are well-characterized hepatotoxins, the ecotoxicological roles of other Microcystis -derived compounds remain poorly understood. This study evaluates the toxic potential of four Microcystis strains - two MC-producing (PMC 728.11, 807.12) and two non-MC-producing (PMC 810.12, 826.12) - in Medaka fish ( Oryzias latipes ) at different life stages. Embryos and larvae exposed to extracts from non-MC-producing strains exhibited pronounced developmental toxicity and malformations, linked to the presence of microginins, aeruginosins, and microcyclamides. MC-rich strain PMC 728.11 induced significant post-hatch toxicity. In adult females exposed under microcosm conditions to environmentally relevant concentrations, strain-specific disruptions were observed in gut microbiota composition and tissue metabolomes. Notably, PMC 728.11 caused microbial dysbiosis, while PMC 826.12 impaired digestive functions, enhancing susceptibility to toxicant uptake. The remaining strains produced milder effects. Our results demonstrate that Microcystis toxicity extends beyond MCs, driven by complex and variable metabolite mixtures. This biochemical diversity poses challenges for bloom risk assessment and raises concerns over unrecognized environmental hazards. These findings advocate for broader monitoring of cyanobacterial metabolites and their mechanistic impacts in aquatic toxicology and environmental health. • Distinct Microcystis genotypes produce unique metabolite profiles • Four genetically distinct Microcystis strains induced various ecotoxicological effects in medaka fish • Microcystis poses threats to survival and development in embryos, and causes dysbiosis and digestive dysfunction in adults • In addition to microcystins, Microcystis produces other bioactive compounds of concern that remain to be fully characterized