Effects of Cyanobacterial Toxins on the Human Gastrointestinal Tract and the Mucosal Innate Immune System

Cyanobacterial blooms occur with increasing frequency in freshwater ecosystems, posing a hazard to human and environmental health. Exposure of human to cyanobacterial metabolites occurs mostly via accidental ingestion through contaminated drinking water or during recreational activities and, most frequently, results in gastrointestinal symptoms. Despite the clinical manifestation, cyanobacterial metabolites are rather investigated for their toxicity towards specific organs or tissues, especially hepato-, nephro-, and neurotoxicity, than for effects on the gastrointestinal tract and the associated lymphoid tissue. The aim of this review was to systematically summarize available literature on the effects on the gastrointestinal tract and the mucosal innate immune system and compile the data from both, in vitro and in vivo studies, focusing on human health-relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects, or both. Furthermore, cyanobacterial bloom lipopolysaccharides, other less studied metabolites and their mixtures have been also implicated to have a role in gastrointestinal inflammation. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. In addition, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites such as aeruginosins, have to be toxicologically evaluated at distinct levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, which can be expected in drinking water supplies.