This really helps explain why we've had such a hard time defining what knowledge is. Ultimately we want to say we know something if it's true, but it seems like we can never be sure anything is 100% true, so we can never actually know anything?

There's always the chance that we're living in the matrix, or that everything is a simulation run by aliens, and that would throw off all the facts about everything in our universe.

When scientists do experiments, they try to completely separate their tests from outside interference, or at least account for any outside effects. That way they can be sure they're just measuring the specific actions they're interested in. But as we ask more and more fundamental questions we eventually run in to the problem that we're trying to learn about our universe from inside our universe. If we could get outside it, we could confirm it's not a simulation, but we can't, so there's lots of things we might just never be able to know.