I attended a talk by a couple of publishers and an agent recently. Both publishers were digital first imprints of major publishing houses (the big six… or it might be five now). Both publishers said that they considered a self-published book to be an ‘unpublished’ book or manuscript and could still be submitted to them for consideration.
If this is the case, why wouldn’t you try self-publishing first? Why wouldn’t you give yourself a deadline (like three years) or a budget to work with, and invest in yourself? When it’s possible to release books digitally into a growing market for under $500 (with no experience, just with a bit of knowledge where to get things done and some motivation), then why wouldn’t you?
You’re not burning bridges with some publishers for making the attempt. You’re not killing your opportunities, you’re actually expanding on them.