Head coach Dean Ryan admitted he has never experienced such a drain on playing resources - Gloucester are without 10 players on international duty tomorrow - and as a result he will hand a Premiership debut to lock Dan Tuohy and include England Under-20 backs Charlie Sharples and Dan Norton on the bench.
"I have never known our resources stretched so far because of our contribution to international sides," Ryan said.
"I think it was impossible to plan back in September for the situation we have faced this week and the personnel we have been without as a result. We want to create an environment where players push for international honours but it has made our task even more difficult ahead of this game.
"But there is massive motivation for us to win a game that has big odds stacked against it. It is about maintaining the proud record and traditions we have of playing at Kingsholm, in front of our own supporters and with the need for a really vociferous response from the team and the crowd."
Ryan's front row will show two changes from the one that lost to Harlequins last weekend. Nick Wood will be partnered by hooker Andy Titterrell and prop Jack Forster because Carlos Nieto is on international duty.
Lock Alex Brown, who broke his jaw last Saturday, will be out of action for a month which means Gloucester unveil a new second row combination in Will James and Tuohy. Tuohy is an Ireland Under-21 international.
He has made 10 appearances on loan at Moseley this season and will be his first appearance in the senior squad.
Skipper Peter Buxton will revert back to the blindside flank and Andy Hazell returns at openside following a slight neck injury. Akapusi Qera will start his first game at number eight.
"We are fortunate that guys like Dan Tuohy, Charlie Sharples and Dan Norton have played regular rugby at Moseley this season and can step into our environment," Ryan added.
Outside the forwards, Gareth Cooper will make his sixth Premiership start of the season in place of Rory Lawson and he will partner Willie Walker at half-back. Gloucester are still monitoring Ryan Lamb's shoulder injury and he misses out for the second successive game.
In the centre, Anthony Allen will make his 16th Guinness Premiership appearance of the season. He has been a try scorer in Gloucester's defeats against Bristol and Harlequins and will be partnered by Jack Adams, who has also scored twice in his four appearances since returning from Moseley on loan because of Mike Tindall's injury.
Mark Foster, James Simpson-Daniel - a try scorer in Gloucester's last three games - and full-back James Bailey complete the back three.
"We are a proud squad and a proud team and I want that to come out in what we do tomorrow," Ryan added. "There have been issues in the last couple of games and we have worked hard on them this week.
"We are up against the form side in the country and that is plenty of motivation."
On the bench, Ryan includes two hookers - Olivier Azam and Jeremy Paul - prop Christian Califano and lock Jonathan Pendlebury.
Mike Prendergast comes back into the squad and will be joined by Sharples and Norton.
Sharples (18) is a member of Gloucester's Academy set-up and after leaving Wycliffe College at 16 joined St Peter's sixth form in the city. He was part of the side that won the Daily Mail Cup in 2006 and this season has scored four tries in 11 appearances for Moseley in Division One.
Last summer, he toured with England Under-18s to Australia and has been called up into the Under-20s squad this season.
Norton has been on loan at Moseley this season and is the club's leading try scorer with seven in 12 matches. He was part of the Gloucester squad that took part in the Middlesex Sevens this season and scored twice against Wasps.
GLOUCESTER (v London Irish, tomorrow, 5.30pm): James Bailey; James Simpson-Daniel, Jack Adams, Anthony Allen, Mark Foster; Willie Walker, Gareth Cooper; Nick Wood, Andy Titterrell; Jack Forster; Will James, Dan Tuohy, Peter Buxton (capt), Andy Hazell, Akapusi Qera. Reps: Olivier Azam, Christian Califano, Jonathan Pendlebury, Jeremy Paul, Mike Prendergast, Charlie Sharples, Dan Norton.
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