Potential effect of <i>Escherichia coli</i> Shiga toxin metabolites in the induction of cognitive dysfunction and stress memory formation in naïve goldfish <i>Carassius auratus</i>

The oral-gut-brain (OGB) axis is a three-way communication process that forms cognitive functions, especially learning and memory (LM) formation. Recent studies showed that the OGB axis is pivotal in efficiently forming and regulating the brain homeostasis mechanism. In this OGB axis, oral and gut commensals play a major role in the bidirectional communication with the brain through the blood-brain barrier (BBB). The dysbiosis of oral and gut commensals results in cognitive dysfunctions like cognitive decline. The present study aimed to study the effect of Escherichia coli induced oral-gut dysbiosis on cognitive memory (CM) formation with the help of a cue-based learning paradigm (CBLP). Other than CM formation, stress memory (SM) formation was also studied with the help of behavioural paradigms like predator exposure test (PET), light and dark box test (LDBT), and open field test (OFT) in naïve goldfish Carassius auratus. The results of the study proved that the OGB axis is possibly involved in the formation of CM by inhibiting stress formation in a habituated, serene environment. Behavioural responses of E. coli-infused groups showed that higher colonization/accumulation of E. coli results in the formation of cognitive decline through the release of shiga toxin (ST) metabolites. It also showed that the release of ST metabolites may disrupt gut dysbiosis through the development of gastroenteritis. Developed gastroenteritis further results in cognitive memory - decline (70-75 %) due to the long-term existence of E. coli-induced oral/gut dysbiosis. Thus, the present study stated the possible effect of E. coli shiga toxin metabolites on the development of cognitive dysfunction in a unique manner.