Here, you're kicking the problem further down the road, though, to another known attack vector: Directory Harvest Attack[1].
In this case, though, the directory (presumably) contains the guid mapping (which - by definition - would have to be a different guid than the object) and would have to process parsing these guids against the users. (This already occurs on recipient receive for some SMTP servers [just before BDATA/DATA] via the email address).
What would one bad email to an email guid do? Would it force rotation of the guid[s] throughout the entire forest? If so, how would that be communicated externally? How would you communicate it for just the one address, if you just changed the one guid?
Would you, instead, have to keep a guid history to check against -- or lose all of the email between possible compromise and the sender's database update? Would you just keep it in the Transport Queue, until manual intervention could check out email between the possible compromise of the guid and new mail would be received for the new guid? That wouldn't scale for large enterprises.
Keep in mind that nothing has to be sent for recipient validation to occur. The SMTP Server[s] just respond[s] to the recipient block with the next step -- but the caller doesn't have to complete the SMTP negotiation from this point, they already have validation if the addresses (even these proposed guids) are valid.
Tarpitting is somewhat of a viable option, here, but it isn't foolproof.
[1] - https://en.wikipedia.org/wiki/Directory_Harvest_Attack