Killing God is the only way forward
The Sampler is God, presented as the ambivalent creator that such a higher power would likely be.
The worm is man's infectious and twisted interpretation of God. The depression, anxiety and suffering we put ourselves through while questioning the motives, or complete absence of, a higher purpose or plan.
God sees us as pigs, though not by insult. We are simply a creation with broad characteristics. He cannot comprehend or understand our complexity, because He is not us and doesn't understand what it is to be us. Just as we can never hope to understand what it is to be a higher power.
Our world is a free range (free will) yard with limited boundaries, where He is content to observe and only compelled to intervene when those boundaries are crossed.
He is just the creator, and not the guide. But the worm promises a different story. A story with rewards for obedience and blind faith. And when you find yourself alone and disoriented when life exposes the harsh reality and loneliness of our creation, you search for meaning.
It is telling that the worm is first inflicted on the young, who have yet to form their own world view and are susceptible to leaders. Other times, the worm is forced on broken people who are searching for answers in their tragedies.
Sometimes a broken person will catch a glimpse of God as He truly is. It is in these moments that we realise His lack of actual presence and control in our lives. This is a profound realisation for the creation, and a disconcerting one for the creator. He has always known this, but it is another thing entirely to see its recognition on the face of something you previously considered to be simply a creation of broad characteristics.
It is only after killing God that we can move forward in a meaningful way. Accepting a life without the assistance or guidance of a higher power means we are left to care for each other. It is in these final scenes of the film that we see once broken characters at their happiest and most compassionate.
With the worm dead, the Thief is exposed for what he is and left empty, with no further way to cultivate and spread the worm. Meanwhile, his impressionable followers look on in shock, and even try to help search for the thing they once believed in. But it cannot be found.
In the end, all we have is each other. It doesn't matter where we came from. We're all alone in it together. And once we all realise it, we can move forward together in unity.