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Leaders Paris St-Germain suffered their first Ligue 1 defeat of the season as Nabil Fekir's second-half penalty earned Lyon victory.
Thomas Tuchel's side took the lead through Angel Di Maria, who fired past Anthony Lopes in the seventh minute.
Moussa Dembele headed in the equaliser after keeper Alphonse Areola misjudged the flight of Leo Dubois's cross.
And it was 2-1 when Fekir fired in from the spot after Thiago Silva had fouled lively former Celtic striker Dembele.
Despite the defeat, PSG are still 10 points clear of Lille at the top of the table with two games in hand.
Lyon are a further three points back in third place.
