Considering what happens to the people of Village because of their participation in Trade Mart and considering what happens to Forest, earth and Village because of what Kira, Seer and Matty ultimately do, it can be argued that the main theme is the idea that cooperation between people, based on their best qualities, their good and useful qualities, can heal the wounds of life and living, even though the wounds caused by people's dark qualities affect earth itself.
When Matty goes to Trade Mart, which Seer disapproves of, Matty is shocked and surprised to see how the people of Village who are there begin to show behaviors and mannerisms that he has never seen before and that are not good or beneficial or useful (except for satisfying greed and avarice).
Some of those who had been among the most industrious, the kindest, ... [now] shouted their wish that the border be closed....
When the people of Village vote to close the border, and Seer asks Matty to go to bring his daughter Kira safely back to Village before the wall is erected, Matty finds that Forest has changed and is becoming ever more dangerous (Forest is symbolically like the people who barter at Trade Mart). In the end, Seer goes--even though he has no vision--to try to save Kira and Matty, who are being viciously attacked by Forest. Trapped and attacked himself, he tries to reach Kira telepathically through her own "seer" gift of future sight.
Because of Seer's contact, Kira encourages Matty to use the good gift he has, although he may not fully understand it--the gift demonstrated when he touched the frog and it was restored--to heal Forest so it will let them live and let them go. Because of Kira, Matty releases everything inside him and touches the earth. Forest is healed, the ground itself is healed, Village people are healed and the urge for a wall is healed. Because three people cooperated together through their best qualities and the best of their gifts, the wounds of life and living in their world were healed: their world itself was healed.
"Ah, Matty, you have more than you know. And people will want what you have." (Seer)
[Quotation by Lois Lowry made in an interview for Scholastic: "My books have varied in content and in style. Yet it seems to me that all of them deal, essentially, with the same general theme: the importance of human connections."]
To me, the main theme in this book is how greed can cause hatred and intolerance.
At the start of the book, more or less everything is okay. The people of the village are so welcoming, so into helping the people who come to their village as refugees. But then that all changes. And it seems to change because of the teacher and the things that are done at the Trade Mart.
It seems to me that the Trade Mart symbolizes greed. When the people start to want more and more (things that are really pretty pointless) they also are willing to hate the outsiders. I think Lowry is trying to say that the two things -- greed and hate -- are connected.