In terms of Culture vs. 40k metaphysics, ideally Culture humans should have been completely distinct from 40k humans, and soulless. They weren't established that way though, so we need a better solution.

I advocate a compromise: while Culture humans have souls, they don't rely on them to the same extent that IoM humans do. IoM humans evolved alongside the Warp, so perhaps their brains don't process emotion the way Culture humans' brains do. Specifically, perhaps the various organics of the 40k universe outsource some of their emotional processing to the Warp, while Culture humans do it all internally. So the Culture would need to rewrite the emotions and instincts of every organic in the galaxy in order to cut off the Warp without killing everything.