Winger Darragh Fanning and scrum half Cillian Willis will also make their first starts for the province. All three have featured in Connacht's opening salvo of Magners League matches as impact replacements and have been rewarded for their efforts.
Galway natives Johnny O'Connor, Andrew Browne and John Muldoon are included in the strong line-up as Connacht look to replicate last season's unbeaten pool run.
Muldoon returns to the side having recovered from a broken arm sustained during Ireland's summer tour match against the All Blacks, and O'Connor has been passed fit following a back injury.
"Bayonne got off to a flyer and are still in the top half of the French Championship, while Harlequins are always difficult.
"If you look back even last season you had Wasps, Gloucester, and some big French teams. It's a competitive tournament. It may not be top tier, but if you look at the teams that have won the Amlin Challenge Cup, they are all big clubs."
CONNACHT (v I Cavalieri Estra): Troy Nathan; Darragh Fanning, Niva Ta'auso, Miah Nikora, Fionn Carr; Ian Keatley, Cillian Willis; Brett Wilkinson, Adrian Flavin, Rob Sweeney, Michael Swift, Bernie Upton, Andrew Browne, Johnny O'Connor, John Muldoon (capt).
Replacements: Dermot Murphy, Barry Fa'amausili, Ronan Loughney, Mike McComish, Michael McCarthy, Frank Murphy, Aidan Wynne, Shane Monahan.