Organizers said the 10th-ranked Spaniard, who made it to the semifinals at the U.S. Open and was due to play his opening match in Metz on Thursday, had been replaced in the draw by Frenchman Kenny De Schepper.
Gasquet, who struggled with injuries recently but won a tournament on the Challenger tour last week in Poland, made a strong start and seal the first set after dropping only four points on his serve. But the Frenchman then failed to convert any of seven break points and dropped his serve twice.
Istomin will be up against lucky loser Yannick Maden in the next round. Gasquet's fellow Frenchman and No. 7 seed Benoit Paire advanced to the second round by defeating qualifier Stefanos Tsitsipas 6-2, 6-4.