Ash himself could be the main antagonist as he is the one doing the betraying.
It could be that Ash discovers some sort of secret about Harrison that he misinterprets. Instead of talking to Harrison about it, he takes actions that seem like a betrayal. For instance, Ash might tell others about this secret, thinking it's for the greater good, but it actually causes a lot of harm to Harrison.
Maybe an ancient evil spirit that has a vendetta against Ash. The spirit could possess the aura guardian and make it turn against Ash. In this scenario, the main antagonist is not really the guardian but the spirit that controls it, and the story would be about Ash fighting this spiritual evil.
It could be a powerful and jealous Galar trainer. This trainer might see Ash as a threat to their own reputation and success in the region. They would then use their influence and charm to turn Ash's friends against him.
It could be a new and powerful trainer who manipulates Anabel into betraying Ash. This trainer might be jealous of Ash's success and see Anabel as a means to bring Ash down.
A powerful and envious Pokémon trainer could be the main antagonist. This trainer might be jealous of Ash's bond with Greninja and decides to break it. He could use dark magic or some sort of mind - controlling device to make Greninja turn against Ash.
It could be a new character who is jealous of Ash and Skyla's friendship. This character might spread false rumors about Ash to Skyla, causing her to feel betrayed. So, this new jealous character would be the main antagonist.
The Pokemon Professor in the region could also be the antagonist. Suppose the professor discovers a rare and powerful Pokemon that Ash is also interested in. The professor, driven by greed or a desire for power, might betray Ash by making it seem like Ash is trying to steal the Pokemon, causing all of Ash's friends and the community to turn against him.
Maybe the main antagonist is an evil organization that has been secretly infiltrating the village. They target Sakura because of her skills and knowledge. They deceive her into believing that her village is the real enemy, causing her to betray her comrades.
It could be a jealous rival trainer. This trainer might have always been envious of Ash's popularity and the loyalty of his harem. So, they plot and scheme to turn the harem against Ash by spreading lies and creating discord among them.
It could be a new and powerful trainer who has a vendetta against Ash. This trainer might see Ash as a threat to their own rise to the top in the Pokemon world. They could manipulate Leaf into betraying Ash to further their own goals.