Butt (hand) and Guthrie (hamstring) missed the opening-day draw at West Brom although they are back in training and should return for the visit of Sheffield Wednesday on Wednesday.
Goalkeeper Steve Harper will take his place in the line-up. The 34-year-old was forced off at half-time and taken to hospital for tests on a head injury after clashing with team-mate Shola Ameobi in the build-up to West Brom's opening goal.
Reading manager Brendan Rodgers is set to return to his first-choice XI for the trip to Newcastle.
Rodgers made nine changes for the Carling Cup clash with Burton in midweek after a flurry of international call-ups and saw his youngsters record a hugely impressive 5-1 win over the League Two side.
However Rodgers is still set to recall Adam Federici, Ryan Bertrand, Jem Karacan, Hal Robson-Kanu and Simon Church for the trip to St James' Park.