Now, I mentioned that Muir took most of October off. While the exact reason for that isn't clear, it probably had something to do with DbD being pulled from syndication in that very month, and him working to shift to its new, purely online existence. 2007 had earlier seen Muir take a break in February as a result of his trip to Iraq, during which he reprinted older comics. The October break saw no such practice. It was (and is) simply a void in that year's calendar.
So what lead to this sudden fall? Well, obviously, nobody's come forward and given a full account, and I suspect that whoever told Muir it was happening gave him a line of guff, but I don't think it's a coincidence that this came after a strip depicting Hillary Clinton in blackface acquired a great deal of notoriety. (Muir was doing another variation of his "Democrats are the real racists" spiel, incidentally, as well as his usual bashing of Hillary.) That said, I think Muir's ability to produce stupid controversy was the final straw, not the sole cause. The fact was that DbD was an unfunny, badly drawn mess and wasn't catching on--the sympathetic newspaper owners who'd given it a chance were likely finding it an embarrassment even before Muir made it a notorious one. In truth, Muir had been fortunate to get syndicated at all, the recipient of the sort of favoritism he was constantly insisting minorities and women got. As I've noted, the search for a Right-Wing Doonesbury has gifted a lot of hacks chances they didn't deserve. Muir was just one of them.
I'd argue the end of syndication and its psychic effects of Muir almost certainly played a role in the shuttering of Mystery Business(tm). (Though as I plan on noting there were others.) And it also definitely fueled Muir's persecution complex, though this remained in its nascent state in the immediate future. But for broader effect--the strip's brief flirtation with mainstream relevance ended, and honestly, to much of the world, DbD barely left a ripple. It would move to an online space that would simply get crazier and crazier as the years passed.
Ironically, the most lasting effects that syndication wrought on the strip were the earliest, from the changes in Jan and Sam's ethnicity, and perhaps the most visually striking, the move to full Sunday strips. For the first three years and two months of its existence, while DbD had Sunday strips, they were standard single-rowed ones. Early in 2006, one year into syndication, the strip began to have full Sundays, though many of the initial batch are lost--for the first six months, the full Sundays ran for one day on the site only and then were replaced by the opening panels only. (Muir mentioned a plan to bring the full comics back to the site, but never did it.) This was almost assuredly about making sure the strip remained in the comic section on Sundays, instead of getting shuffled to the editorial page. But of course, Muir kept up with it afterwards.
Indeed, it's safe to say the brush with syndication would help annihilate the foundations of the strip as it had been. But then, Mystery Business(tm) had been on shaky ground for awhile, as we're going to see.