Scotland international Ally Hogg will captain Newcastle in Thursday night's Amlin Challenge Cup opener against Bourgoin at Kingston Park.
Hogg leads a much-changed side from the one beaten by Harlequins in Aviva Premiership action last weekend.
Number eight Hogg, wings Luke Fielden and Charlie Amesbury, together with prop Grant Shiells and lock Filipo Levi, are the only players who remain in their starting positions.
Elsewhere, Jeremy Manning switches from full-back to replace fly-half Jimmy Gopperth, with Gcobani Bobo and Luke Eves forging the centre partnership and Micky Young starting in the number nine shirt.
Premiership newcomers Exeter and French club Montpellier are also in Newcastle's pool, with three Heineken Cup group runners-up joining Challenge Cup action at the quarter-final stage.
Newcastle will fly the English flag alongside Quins, Sale Sharks, Leeds Carnegie, Gloucester and Exeter, but the French contingent looks particularly strong, being spearheaded by twice Heineken runners-up Stade Francais.