The way I see it is that bombs are found in video games, and we know that Isaac plays them; the Game Kid is the primary reference, but SMB Super Fan, Dr. Fetus, and the various Gishes knocking around (both as items and enemies) are also proof too. The clincher's the arcade, one of the few rooms in the game that will not deliberately hurt you; Isaac might think that getting an enemy in a treasure room isn't fair, but he definitely sees arcades as safe space.
See, it's my belief that Isaac had a fairly normal childhood up until the death of his sister (ending 12); after which, Isaac blamed himself for everything bad that happened. His father was utterly unable to cope and left the household, while his mother slowly got angrier and angrier with him. I don't think she's trying to kill him (although if you read Dave Pelzer's autobiographies, his mother does stab him with a kitchen knife; I can't help but wonder if that's where McMillen got the idea from); I think she's becoming stricter with him out of her own grief, which also made her turn to God as a source of comfort and salvation. The opening cutscene is more important than people think it is; we must remember to view them through the eyes of a child, who believes he is being punished unfairly for being grounded and having the odd toy confiscated.
Think about the order of the levels and what they represent. Isaac starts low and goes lower until the end of the Depths/Necropolis, wherein he fights his perception of his mother as an unknowable titan aiming to crush him. Then come the Womb/Utero levels; in these, Isaac is trying to analyse his own feelings of guilt, confronting his mother's own feelings on the matter in his head over and over again until he realises that they all stem from maternal feelings of protection and the fact that she thinks she failed her daughter, as shown by the transformation of Mom's Heart into It Lives. After that, the child has a choice; go down, or go up? Fall or rise? Sheol's levels are hard because Isaac is wallowing in his own perceived damnation, and the fight with Satan shows that nothing has changed - the similarities with the Mom fight are pronounced for precisely this reason. The music in the levels is muted and downbeat, demonstrating the depths of Isaac's misery, misery he feels is deserved. When he overcomes Satan, the ending demonstrates that nothing has changed for him; he is still in the box described by the Twinfinite article, resigned to his fate as a bad child.
However, should he choose to rise into the Cathedral, the rooms are hard for a different reason; Isaac, rather than accepting his fate, is trying to change it. The music is similar to Sheol, but more hopeful; angelic rather than demonic. He is trying to change his mind and get rid of the toxic beliefs he held. This is also why the rooms here are harder than the ones in Sheol; it's much more difficult to change your mind than it is to stay set in your beliefs. It's also felt in the change in final boss battle; the fight with Isaac is almost a bullet-hell boss, and there are no other boss battles like it earlier in the game. This is Isaac trying to change how he sees himself; and for Isaac, it's almost the hardest thing he can do.
If you have the Polaroid, however, the metaphor becomes slightly altered. Isaac can now go through the Chest upon breaking his self-image and rebuilding it into something stronger, represented by the four golden chests in the starting room. As long as he has the means to do so, Isaac is able to make himself stronger, and though the rooms are the hardest in the game by far (because Isaac is confronting more and more uncomfortable truths about himself), there is more reward at the end of it. Finally, with the boss ???, he confronts the root of his problems; the corpse of a child, blue with rot. ??? represents his grief, from which stemmed the majority of his self-esteem and self-image issues portrayed by the fight with Isaac; the character model curled on the floor in the centre of the room is ??? rather than Isaac, the boss's first stage also produces flies, the symbolism is obvious. However, like the fight with Isaac, the body rises in a Jacob's Ladder, slowly but surely ascending to Heaven and granting Isaac salvation in the process. He believes God has forgiven him, and in believing so, forgives himself. It's about as triumphal as a game like this can get. All of this is explained by the final ending, which you only get by defeating the boss.
This, I believe, is why items change your image throughout the game. I think that TBoI is a game about the perception of the self, and the effects of the various passive items on Isaac's body are a discussion on how external stimuli affect the self-image of a vulnerable child. The more you progress through the game, the more you pick up, the more you change, the more you can grow. This is how I think it ties into the "box" theme touched on in the Twinfinite article; Aether showed what happens when you don't get out of the box, Time Fcuk showed you can get out of the box, and The Binding of Isaac says that it's difficult to do so but the most rewarding thing you can do.
By the end of the Chest, Isaac has achieved self-actualisation. He has overcome his fears, his doubts, his guilt, and his shame. He is at peace with himself and with his God. He has earned his happy ending, and through understanding how it is a happy ending, we are exhorted by the game to get that ending for ourselves, no matter how hard it might be. KBO, says Edmund McMillen. KBO.
Of course, Rebirth could throw this all out of the window in an instant, in which case I'll look ever-so-slightly ridiculous. =D