Other changes from the team that started at Leicester Tigers last weekend see Rob Cook return after recovering from a stomach bug, and Dan Murphy come in for Nick Wood at loose head prop.
Saturday's game will be the third time that the two teams have met in five weeks, and the fourth time they've squared off in all competitions so far this season.
Gloucester have won all three meetings to date, but Director of Rugby Nigel Davies insisted this week that there will be absolutely no room for complacency.
"It's a very important game for us, and a very important game for them as well for different reasons.
"London Irish can be dangerous, they're very unpredictable and always have that ability to hurt teams. We have to be mindful of that and respect that. If you're loose and give them half chances, then they will take advantage.
"You have to be very careful as we have played them so many times, we don't want to become too complacent in terms of what we expect from them.
"They'll keep probing for opportunities, and they have quality players who can change a game in an instant. When you play a team like that, you have to be 100% focused all the time.
"So, we've put in a lot of work this week analysing them again. We're pretty comfortable that we have a game that will serve us well if we're accurate and execute well."
Gloucester Rugby:
Rob Cook; Charlie Sharples, Mike Tindall (capt), Billy Twelvetrees, Shane Monahan; Freddie Burns, Jimmy Cowan; Dan Murphy, Huia Edmonds, Shaun Knight; Tom Savage, Will James; Sione Kalamafoni, Akapusi Qera, Ben Morgan
Replacements:
Darren Dawidiuk, Nick Wood, Dario Chistolini, Peter Buxton, Matt Cox, Dan Robson, Tim Molenaar, Martyn Thomas