Can cyanotoxins explain the clinical features of the thermal crisis in balneotherapy?

Microbial biofilms communities in mineral waters and hot springs have a particular composition with species belonging to different groups such as epsilonproteobacteria and gammaproteobacteria or different siderobacteria and other chymoautrophic organisms, in addition to certain bacillaryophytes, chlorophytes and especially cyanobacteria. Balneotherapy can cause adverse reactions to the usual doses of application of treatments, that consists of a non-specific clinical picture, the so-called "thermal crisis" or "balneointoxication". Despite its clinical similarity (gastric discomfort, hepatic congestive outbreaks, cutaneous reactions, etc.) with that observed in acute cyanotoxin poisonings, thermal crisis has never been associated with the abundant growth of potentially toxic cyanobacteria in the mineral water sources. The aim of this work was to verify the hypothetical involvement of cyanotoxins in this clinical picture. Samples from mostly sulphurous water sources, with thermal characteristics ranging from cold to hyperthermal waters were analysed. ELISA (both in solution and in cellular matrix samples), LC-ESI-HRMS (in cellular matrix samples), and analysis of potential toxicity by means of a standardized bioassay were carried out. The toxic effect observed in the toxicity bioassays in one third of the sources may be related to the existence of microcystins and nodularins and even with other cyanobacterial peptides detected. In addition, several responses observed in the toxicity analyses reflect a pattern, probably linked to a type of hormetic response (hormesis is an adaptive response to low levels of stress, characterized by a biphasic dose-response curve).