The jury's out on 'you guys' - some people like it, some don't, some don't care. For some people, it triggers gender dysphoria: http://www.gendertrust.org.uk/gender-dysphoria/
(link CW: refs. to self-harm, suicide, etc.) I obviously can't speak for Trans people, but generally speaking, if there's a particular phrase that causes these feelings, then that'd be why someone would react like that.
The singular 'them' is something that's been in English forever - I promise: https://grammarist.com/usage/they/
It's used mostly by Non--Binary people (people who don't feel 100% like a man, or 100% like a woman) - but there's also a whole load of other pronouns that NB people use, known as neo-pronouns (you're not expected to automatically know - if someone uses neo-pronouns, they'll tell you.)
Most people are pretty chill, as long as you act respectfully towards them, and don't insist on calling them something they've requested you don't <3 <3 <3