High Brow is challenge #2. Isaac begins this challenge with Number One, E Coli, Butt Bombs, Flush!, and Petrified Poop. The goal is to defeat Mom. This challenge is unlocked by default.
Starting with Number One limits Isaac's range significantly. Getting close to enemies is required to defeat them.
- Flush! can be powerful when dealing with a large number of enemies, such as in a 2x2 room. Turning all the enemies into poop allows for rapid clearing of rooms, and Petrified Poop increases the chance of those poops containing pickups.
- E. Coli can turn enemies into poop. Given the short range granted by Number One, enemies will be more likely to do contact damage. Enemies that do not do contact damage (Black Flies, Mulligan, Hosts, etc) are valuable, as they can be transformed into poop with no drawbacks.
- Skatole is a highly useful item, due to the amount of Black Flies it creates that can be transformed into poop.
- Butt Bombs gives 5 extra bombs to start with, which can make items or Secret Rooms easier to find in the first 2 levels.
- Because of Number One's synergy with Brimstone, it is highly recommended, despite the Health cost.
- While it is slow, Mysterious Candy can be helpful if resources are scarce in a run.