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Assuming an individual has otherwise sufficient dental hygiene (brushing twice a day, flossing daily, tongue scraping, avoiding acidic foods and drinks, etc.), is there any potential for bacteria from uncleaned dental guards to cause any appreciable tooth decay, or demineralized spots on the teeth?

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https://www.ncbi.nlm.nih.gov/pubmed/23016013

PAM (protective athletic mouthguards) are contaminated by microorganisms that have the potential to produce oral and systemic diseases. They should be sanitized daily and changed when they become sharp and/or jagged.

And a commentary from the AGD on this study

"These concerns are similar to using an infected toothbrush repeatedly or using silverware that has not been cleaned properly," says AGD spokesperson Bruce Burton, DMD, MAGD, ABGD. "Although a mouthguard is recommended to prevent permanent damage to the mouth and teeth, we know it also has the potential to be a reservoir for bacteria that can cause gum infections or the bacteria that help promote tooth decay."

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