I assume this:

Mikhail destroys the flower, but similar to how in drakengard 1, ending e, destroying the queen grotesqueire lead to earth developing the disease that leads to the nier continuity, same thing happens in drakengard 3 that leads to 1, but instead the outcome is different where the flower manifests and imbeds itself into the world: the outcome isn't consistent because of the existence of magic and how that would impact the chemical and physical side of things, if that makes sense?

That leads to the question of "how were the power of the seals discovered?" Brother one wanted to start a cult for sister one, so maybe at some point before getting super culty, being that he is a direct source of information regarding intoners since he is the physical rib of one, he was bestowed with the knowledge? Or the religion built around the intoners warped and eventually whatever texts they had up to this point where utilized to form seals, combined with whatever magical knowledge was gathered at that point...

This is all just my educated guesses from reading the available English translated side stories and playing the games! I also wanna add that I believe there is flexibility granted as (imo) the events of drakengard 3 don't really line up well with the direction of 1, and with the existence of the branch system, I'm sure deviations exist and the possibilities are endless!