The configuration for running 50 of these boards is very similar to the configuration for running 5 of them, only you need 50 I/O pins dedicated to the XSHUT pins instead of 5. The Uno does not have that much I/O, so you would need some kind of multiplexer like the I2C GPIO expander board you mentioned, though an Arduino Mega 2560 might work for an application like that without one.
You might look at some of the resources for the MCP23017 available at Adafruit for more information about how an I2C GPIO expander works.
Also, you might run into issues with the electrical properties of an I2C bus with 50 devices on it and you might need to solve some engineering problems for your system to ensure good signal integrity to all of the devices on the bus. We do not have any specific advice for getting a bus with that many I2C devices to work well, but you should be able to find whitepapers that discuss that more thoroughly.