Learn Italian: La nuova guida è inesperta ma gentile. - The new guide is inexperienced but kind.

It is formed by adding the negative prefix in- to the adjective esperta (experienced). Just like in English, this prefix flips the meaning of the base word to its opposite, meaning "inexperienced".

Could I use the prefix dis- or s- instead of in- to make this adjective negative?

No, negative prefixes are tied to specific words, and you usually have to memorize which one goes with which base word. While dis- and s- are very common (like in disordinato or sfortunato), the opposite of esperto is always inesperto.

If the guide is a man, would the sentence change to il nuovo guida è inesperto?

No, the noun guida is always grammatically feminine, even when referring to a male guide. Because the noun is feminine, all articles and adjectives describing it must stay feminine, so it is always la nuova guida è inesperta.

Why doesn't the adjective gentile end in -a to match the feminine noun guida?