The exact phrase "the spice must flow" doesn't appear in Frank Herbert's original six Dune novels. There are some close calls, but, the reason why we remember this phrase is that it is spoken by one of the Third Stage Guild Navigators in the 1984 David Lynch version of Dune. If you were a casual fan, you would look at that zany looking dude who says, "the spice must flow...I was not here" and think he was a trippy David Lynch space alien.
But the Third Stage Guild navigator is not an alien. That's a human who has been mutated by longterm exposure to the Spice. Outside of extraterrestrial animal life, there are precisely zero space aliens in Dune. Arguably, this fact is part of what makes Dune so successful. Common science fiction ideas don't really drive the story of Dune, mostly because alien life is totally left out of the equation. Here's how that works, and why Dune's world-building is super-reliant on a lack of aliens.
Although we tend to think of Dune as dense and complicated, it's not really a work of hard science fiction, at least not when it comes to the way the story unfolds. Dune doesn't really speculate on how science fiction concepts transform the world but instead takes a galaxy transformed by several sci-fi concepts (mostly interstellar travel) as a given, and then just tells a story from there. You could argue that Frank Herbert did the hard SF world-building before he actually wrote the novels and that hard SF exists beyond the page. For example, actual astronomy is a huge part of the Dune backstory — 36 Ophiuchi B (a real star in our universe) serves as the star system for Geidi Prime, while the real star Canopus is the system where the planet Arrakis (Dune) can be found.
But these facts are not a big deal in the actual story of Dune, and (arguably) not things the reader remembers. Instead, the fact that real astronomy is used as the backdrop for the Dune star systems helps lend the novels an air of credibility. It doesn't transform Dune into hard SF, but the presence of actual stars in the books does gesture at one huge decision Herbert made with the novels. Though it's not stated outright, the books basically operate on the premise that the Fermi Paradox is totally legit.
The Fermi Paradox and Dune
The basic premise and overly-simplistic premise of the Fermi paradox is that the reason there are no aliens is that if there were, we would have known about it by now. Because the Fermi paradox originated in the early 1950s, it's not super-clear that Frank Herbert was influenced by it, but the way Dune is written seems to proceed from the premise that as human beings expanded out into the galaxy, they did find alien life, they just didn't find any intelligent alien life.
This means Dune avoids having bipedal "humanoid aliens" popping up on different planets à la Star Trek or Star Wars. In franchises that have bipedal humanoids, the in-universe explanations range from parallel evolution to panspermia, to zero explanation at all; just deal with it. Again, Herbert avoids having to explain humanoids living on other planets because all the people living on other planets in the Dune universe are, in fact, humans. "Space aliens" as we might think of them, are basically left out of the equation in the world-building of Dune.
Again, this assumption isn't stated outright in the text. It basically exists before you start reading. Herbert doesn't really get into why there aren't aliens, because it would be a weird question to answer in a universe that just doesn't have them. Put more simply, the absence of aliens in Dune speaks volumes.
Dune's sandworms are the exception
Okay, so Dune is a science fiction work that lacks aliens, but at the same time, an alien creature — the Shai-Hulud or "sandworm" — is central to the narrative. Without the sandworms, you don't have the Spice, and without the Spice, you don't have the story of Dune at all. Plus, in the later books, Paul's son, Leto II, becomes part-human, part-sandworm and lives for thousands of years. So, in this way, a very specific type of alien animal is actually what Dune is all about.
Now, is the existence of a giant worm-like alien animal more likely than the existence of a bipedal grey alien with big Area 51-oval eyes? Well, that's kind of debatable, and it's very tempting to say — yes, worm aliens or aliens with tentacles are more "realistic" than aliens with arms and legs. But some of that is connected more to our feeling of what would be truly "alien" on another planet. Dune 2020 director Denis Villeneuve famously brought tentacled aliens to life in the 2016 film Arrival, which was praised by critics partially because it gave us aliens that felt more "real." This is why it's barely shocking that Denis Villeneuve is also doing Dune — the connection between the aliens in Arrival and the sandworms in Dune is fairly simple. From a biological perspective, these creatures feel more plausible than "conventional" aliens that have arms and a face.
This isn't to say that the sandworms are exactly sentient (again, very debatable) but to pretend like they aren't aliens would be nuts. The Shai-Hulud are totally aliens, and without them, you don't have the God Emperor of Dune, and you certainly don't have Third State Guild Navigators.
But, most interestingly, the sandworms in Dune represent another paradox. Because the worms help create the Spice, and the Spice makes interstellar space travel possible, that means alien animals are the sole source of how humans make contact with alien animals.
In other words, the spice must flow because, if it didn't, then the only aliens in Dune (the sandworms) would get lonely.
Dune 2020 is still slated for a December 2020 release, though that is subject to change.