Have we ruled out simple substitution unwisely?

[Stefan Wirtz_2]

I thought it may be genuinely worth debating this. [..]

Yes it is.

Coming from this thread's title, I would even say that a lot of unwise things happen(ed) around the Voynich Manuscript, and insisting that "it can't be simple substitution" (= an unknown alphabet) is one of them.

One hint is the a , just widely accepted as an 'a'. I never saw a ressourceful doubt on this being anything else than an 'a'. 
As it never appears at the end of VMS words, Wilson once suggested that the y might be the "end-of-word-version" of 'a', so in this use having 2 writings of letter 'a', depending of positions.
a occurs in plain sight and at positions where we may expect this vowel in natural languages -- at least those appearances do not obstruct this.
The thing is: if the, in nearly all languages, rather frequent letter 'a' appears at "normal" positions and density, what worth would have any enciphering that left it there? 
A cipher with such flaw would have been cracked soonest, but latest with today's computer powers.

About predictability: there are lots of conditions forcing a (kind of vowel) to follow consonants, go's and no-go's for letter combinations, etc. 
That depends very much on a source language - which we don't know for VMS.

I did never see even only a valid list of 'characters' of Voynich -- meaning those letters who appear in words, occasionally in unique combinations, which would allow to say that a sign or a short combination of signs is meant to be a 'character' at all.
In your example, I don't clearly see eee : since there seems to be a rest of ink between the second and third e ,
this may as well be an ece