I recall a story that featured junk food vitamins, where small evolutionary changes allowed utilization of newly available substances. A few people who shifted to a "helthier" diet got very sick, and it turns out that one lad had a slightly more efficient enzyme for something or another and it needed the caramel coloring in soda drinks to work.
Think about how that might happen: the mutation spreads and eventually someone has copies only of the new form.
Look at history: humans can't make vitimin C, and it's readily available in our diet.
If done intentionally through genetic engineering, new metabolic mechanisms can be invented that are highly desirable. And to save on engineering more pathways to synthesize various parts it is decided to supply that ready made. Maybe some stuff can't be readily made with normal metabolisms, but is synthesized at high temperatures or with toxic feedstocks.
Now lets make that new required thing be toxic to unmodified humans and most animals.
As for whole scale nutrition, note that food is made of the same stuff as our bodies. For normal proteins, sugar, etc. to not work, the body would have to be very different.
Perhaps transhumans add more features to themselves over time. Something better than collegen that doesn't wear out and is stronger, used in skin and other places; bones are totally reingeneered chemically. They will need more materials innthe diet, perhaps including titanium instead of calcium.
Now it seems odd that old-style biology food would be not tolerated. Even if some constituents are useless, what's wrong with it? There needs to be some reason why something common in normal food woukd be dangerous to them. How about: the digestive system is changed to handle the wierd feedstocks needed by the upgrades, which are things that are non-biological and normally toxic. Something common in normal food interferes with the new pathways. It's hard to make them coexist since in digeation everything is mixed together: how do you keep A moecules away from B processing and vice-versa?