I mean, they don't really change anything about the run itself, right?

There was an issue back in 2017(?) where a certain mod that changed the prompts to DS4 prompts was found to be having an impact on other areas of the game. I can't remember what exactly the issue was though since it was so long ago but if you searched in the Discord server you could probably find it.

To be extra clear, if you submit a run with the mod active the run will be rejected.