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The Mississippians faced significant disruption with the arrival of the Spanish, particularly Hernando de Soto, in the 1540s. The expedition brought new diseases that devastated their population, as they had no immunity to these illnesses. Additionally, the Spanish sought resources and territory, leading to conflict and further destabilization of Mississippian societies. This interaction marked the beginning of profound changes in their culture and way of life, ultimately contributing to their decline.

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