Ash would likely be shocked at first. He's so used to seeing the good in people, especially fellow trainers. But then he'd probably get angry and determined to set things right. He has a strong sense of justice, so he wouldn't let the betrayal go unpunished.
Some fanfictions might have Misty betray Ash. Perhaps she gets lured by the promise of power or some valuable reward. She could be tricked into believing that Ash is no longer the friend she thought he was and that betraying him is for the greater good.
Ash might meet a strict teacher who has no idea about Pokémon at first but gradually becomes interested in them. He could also meet a rival in school who challenges him not only in academics but also in Pokémon battles.
Pikachu would most likely be there. Since Pikachu is Ash's closest companion, it would be involved in any story related to Ash. Maybe Pikachu could also have some sort of interaction with Mew, like being a bit jealous at first of Ash's new connection with Mew.
A fellow trainer in Alola could betray Ash. This trainer might be envious of Ash's success as a champion. He could secretly work with Team Skull or some other antagonists to undermine Ash. For instance, he might give false information to Ash about a battle location, leading Ash into a trap.
His rival could be the one to betray him. Rivals are often jealous and competitive. If Ash's rival saw an opportunity to gain an advantage by betraying him, they might do it. For instance, they could lie about Ash to the Pokémon League, getting him disqualified from important battles.
Ash develops by learning new strategies. In Pokemon Conquest, battles are different, so he has to adapt, which makes him more versatile. He also develops his relationships with new Pokemon, which broadens his understanding of different Pokemon types.