Yeah new to guix here but I think flatpak is the suggested and reasonable approach to combine with immutable desktops

Might be worth looking into immutable distros (nix, guix) and their home management systems, or containerised apps (flatpak, where you can inject config). A lot of tools are hardcoded to non standard locations so it’s kind of a losing battle by default. A similar strategy would be to use permissions or mount certain folders as read only.

Yay more options

Have you also tried nix, if so did you have any particular reason to stick with guix (maybe the Foss aspect)?