There's an argument (from the philosopher Nick Bostrom) that if people are going to be running universe simulations someday, then we're probably in one.
There's no need to simulate every quark and electron and gluon and whatnot in perfect detail. The simulation only has to be good enough to convince us it's real. There's no reason to assume that future civilizations will run one simulation and then unanimously decide to give up on the whole idea forever, so there would probably be lots of simulations. With all those simulations, how can we assume that our world is the one real one?
The converse is that if we're not in a simulation, then those kinds of simulations will probably never happen.