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The most likely cause of the database disconnection in Devilbox, Isotope, or Contao when XDEBUG is set up but remains unused is the increased resource consumption by the XDEBUG extension. XDEBUG is a powerful debugging tool that can consume a lot of system resources, including CPU and memory. When XDEBUG is enabled but is not being used, it continues to consume system resources, leading to bottlenecking issues, which can cause disconnection of the database or other related issues. Therefore, it is advisable to disable XDEBUG after debugging to free up system resources, ensuring smooth and seamless operations of the system.