De Bruyne came on to score a fortuitous 85th-minute goal on Saturday, but the damage had already been done. Jeffrey Schlupp's first-half goal cancelled out Ilkay Gundogan's opener and an Andros Townsend wonder strike was added to by Luka Milivojevic's penalty.
The result means City are four points behind Liverpool at the summit, with back-to-back trips to Leicester City and Southampton to come before they host Jurgen Klopp's side on January 3.
Aguero, who replaced Nicolas Otamendi as Guardiola chased the game at 2-1, and De Bruyne started the midweek Carabao Cup triumph at Leicester City following recent lay-offs, while Guardiola watched John Stones turn in a mixed performance at the base of his midfield in Fernandinho's injury-enforced absence.
"When you win I am a genius, when you lose I am not good," City's manager told a post-match news conference.
"I don't know what would happen if Kevin starts or Sergio starts. Dinho is injured, yesterday he felt that problem. John played so good in Leicester [in the unfamiliar position] so I wanted to give another option for [defending] long balls.
"He played good except for one ball. I admire and give credit to people who try and adapt to positions they are not used to."
With a hectic and now pivotal period to come in his team's title defence, Guardiola denied he was being overly cautious with two of his prized assets.
"Of course he could have played - I decide to play the other ones," he said of De Bruyne, whose action has been limited by a pair of medial knee ligament injuries this season, although the Belgium star now has two goals in as many appearances.
"Gabriel [Jesus] scored two goals in the last game here versus Everton. Sergio needs more time to get rhythm.
"Kevin's condition is better. We put in six or seven players with fresh legs. That is going to happen in the future.
"When you have a lot of games, everyone has to play. The guys who played did absolutely everything."
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