If the Federation is a democracy, as we all assume, then Starfleet and it's exploration programs are bound to wind up the subject of popular vote sooner or later. Not hard to imagine the average voter blaming Starfleet for exposing them to the Borg, Dominion and whatever else. The Federation could very well swing toward a more isolationist mindset. Hence, the absence from the delta quadrant in the 31st+ centuries.
The problem with this scenario is that it relies on the assumption that the Federation electorate is stupid and irrational.
Or 51% of them, anyway.
Stupid and irrational are traits that seem to be abundant in the Federation. Just about everyone whose name isn't on the opening credits possesses at least one of them. Gotta make the main characters look good, after all.