Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

Abstract

Background: 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. Main body: 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. Conclusion: 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.

The water chemistry and microbiome of household wells in Medawachchiya, Sri Lanka, an area with high prevalence of chronic kidney disease of unknown origin (CKDu)

“…In particular, the toxin-producing cyanobacteria genera, including Microcystis and Cylindrospermopsis , as well as Leptospira interrogans can lead to kidney disease 14 , 18 , 24 , 25 and have, therefore, been put forward as potential causes of CKDu 21 , 26 , 27 . Significant increases of cyanobacteria in freshwater resources in Sri Lanka have occurred over the past century as a result of eutrophication and rising temperatures 21 , 28 , demonstrating that altered water chemistry is likely to promote the presence of pathogenic bacteria in this region.…”

Microcystin-LR Does Not Alter Cell Survival and Intracellular Signaling in Human Bronchial Epithelial Cells

“…Out of 11 different human OATP isoforms, the ability to transport MC-LR was confirmed for OATP family 1 (OATP1A2, 1B1 and 1B3), while no MC-LR transport was detected for the OATP2B1 [50]. To the best of our knowledge, the other OATP isoforms have not been investigated for their ability to transport MC-LR [36]. Regarding OATP expression in human lung tissue, studies utilizing microarray and RT-PCR reported expression of OATP2B1, 3A1, 4A1, and 4C1 [51,52], while targeted proteomics analyses detected OATP1A2, 1B3, 2A1 and 2B1 [53].…”

New Data on Cylindrospermopsin Toxicity

“…It covers the large surface of the gastrointestinal tract, which is in contact with toxins in water and food, and is the common barrier against their absorption in inner-body fluids. Over the last two decades, the effect of CYN on the gastrointestinal tract has been tested using in vivo and in vitro experimental models (for details see [ 25 ]). A large amount of CYN-containing extract (2.5–8.3 mg/kg) was applied in the in vivo study [ 26 ].…”