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 against the Royals at St James' Park. 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.
Dutchman Tim Krul replaced Harper for the second half and produced several superb saves as the Magpies secured a 1-1 draw thanks to Damien Duff's equaliser.
Left-back Danny Simpson goes straight into the squad after joining on loan from Manchester United.