Can you enjoy this game and experience a significant portion of its content without using guides?

I don't agree with that exactly but can appreciate it's a good warning that not using external help could be frustrating. I found Preach doing this interesting, I thought he would struggle a lot more than he did, but he made it through the campaign very easily, only getting temporarily stuck in lab. He did choose a strategy that was good for a new player, using marauder and struggled when playing witch, but I don't think using external information is mandatory, it's just a massive advantage if you want to learn faster.

A guide is not the most necessary tool in my opinion, but making a build from scratch without POB, learning mechanics without wiki, crafting without a tool that tells you what mods can roll, playing maps without a lootfilter, is an uphill battle. I think the use of external information is relied upon a bit too much by the game, but some people do like figuring this stuff out on their own. There are somethings where this becomes excessive. How does a player learn quality on gear helps to link? I don't think it is in the help menu and don't think it possible to learn by experience. There are many mechanics like this. It's possible to progress without knowing it, it's also possible to get a six link without knowing it, but is it fun to play without knowing this, or is it fun to learn at some point after you've been wasting a large amount of crafting mats that could of been saved by tabbing out of the game and reading information.

Yes, with a but.

You can absolute get to the end just by more or less killing your way forward. However, good observational learning will go a long ways to making it less painful. The game is pretty bad at explaining itself, but is generally consistant in its core concepts. Smashing gold barriers wondering why your arrows arn't doing damage, or figuring out why you keep dying when your screen clearer goes off in the Imperial Gardens are things the game won't 'tell you' but do make sense when you look at them and think about what's happening. Of course these are things that guides might help with too.

In addition, while LOTS more builds than the internet claims do in fact work just fine. Sure they may not delete a map in under a minute, and might have to have a punching match with later bosses for a few minutes. But they will work. But that's not to say any ill conceived idea will work. So be ready to fail, be willing to look at your tools and ask, "What isn't working here, and can I drop it or find a way to make it work" and "What is working here and how can I make it better". A lot of this is thinking and reading things carefully, again PoE puts the information in front of you, but it's pretty bad at really making it clear due to how complex some elements are (doubly so when you get into the wierd stuff like totems, brands, links and the like). And a visit to the wiki now and then to learn a more niche mechanic can help, but if you're the type to just be willing to chew on it for a few hours, try out that new skill with a few different support set ups just to see how it feels, you'll find a deep well of possibility. But if this sounds as fun as dental work to you, I'd suggest finding a more well explored road in the form of a guide and roughly stick to it until you figure out the basics.

A bit part of this, and of PoE is asking a question of 'how often are you willing to fail and still feel like you're having fun'. A lot of major titles (be it other ARPG or just like a shooter), this is often 'Not ever', or at least 'rarely'. A lot of people find failing or losing very frustrating, particularly when it happens a lot at one point, so games design around it (some even making hidden mechanics where enemies automatically get weaker if you fail too much). And to be clear, that's okay, its okay not to play a game that beats your ass all day. But PoE isn't the game that wants to hold your hand, and its largely built for the players that chaffe at that sort of guidence. The platonic idea of the 'gamer survivor' for whatever that is worth, it wants to rough you up some, so you feel accomplished for overcoming it. So if you're tha player that knows they'll get a bit frustrated the tenth time Malachai kills you and you don't know why, I'd suggest a guide. If you are the type of player to think that's a good time, or at least, takes it in stride, then no, a guide isn't necessary (and might spoil some of the fun, like a Dark Souls Guide warning you about rough ambushes, Lautrec or Patches).

As always, feel free to PM me here on the forums if you've got a particular question and don't know how to find the answer, always happy to help and supply information or a helping hand.