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Eastern indigo snakes are indiscriminate carnivores known to feed on virtually any vertebrate they can overpower. They are a robust and domineering species that overpowers their prey by using strong jaws while pinning the prey item to the substrate with a body coil; often swallowing the prey alive. When feeding on snakes they may chew until the prey is immobilized, and then swallowed head first. Eastern indigos have a high degree of immunity to the venom of sympatric snakes, and suffer no lasting injury if they are bitten by venomous snakes on which they prey.
Eastern indigo snakes are known to feed on fish, frogs, toads, small alligators, hatchling aquatic turtles, hatchling and juvenile gopher tortoises, lizards, other snakes, birds and their eggs, and small mammals. An adult eastern indigo found in southern Georgia regurgitated a pigmy rattlesnake (Sistrurus miliarius), a hatchling gopher tortoise, a southern hognose snake (Heterodon simus), and a southern toad (Bufo terrestris). Eastern indigos are sometimes cannibalistic but observations documenting this for wild snakes are rare.
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