There's actually been quite a lot of sub 2:15 marathoners who have taken on Comrades/100K WC. As another example, Jonas B beat several 2:13-2:16 guys at the 100K WC, and yet he's only a 2:22 marathoner and finished 2nd at Comrades. As with Comrades, there's still all kinds of variability with marathon/100K times. Yet, it continues to hold true that it's usually the 2nd-3rd tier marathoners who prevail, while the faster marathoners perform good but not exceptional as hypothetically assumed.
Notably too, the South African team has gone to the past two 100K WCs. Was it 'easy' for them? No. As mentioned, a flat course is faster and more repetitive/stressful on your legs/gut/mentally, vs a more variable course like Comrades that changes up the muscle usage. I've felt much fresher on rolling road ultras vs the flat road ultras that destroy you in every way. Also of interest, there's more women who have faired better at 'both' Comrades and flatter 100K WCs. Women seem to usually pace more reasonably and within themselves, vs the men's races which tend to be more tactical.
As far as the metabolic shift, it's the point of glycogen depletion when running at 50 mi-100K pace on road. I say 35-40 mi based on personal experience of where I consistently start to catch faster men or open a gap. I've noticed it too following races. I think with the slower, fartlek-like pace on mountain trail and variable muscle usage, you're mostly sipping glycogen. It's not the same 1:1 level of whole body depletion and repetitive strain as high intensity road ultras. For this reason, I'm inclined to believe more variable gaits and skill sets (steeple-marathon) can thrive on mountain trail ultras (50K-100K). The longer the distance though, the more it starts to be comparable in whole body fatigue to road ultras.
Altogether, what is hypothetical doesn't reflect reality. Faster marathoners are usually 'good' at ultras but are still more often than not beaten by slower marathoners who are plausibly more slow twitch.