How do you edit content of a Drupal\Core\Render\Markup instance via a preprocess function in Drupal 8?
You can't edit the content. There is no public method to change it.

Usually you simply override it with a new instance:

$variables['fields']['title'] = Drupal\Core\Render\Markup::create('New content');


The double underscore indicates a magic function, which would be called automatically if you use the object in a string context. This is readonly. 

If you want to add a string to the old markup, that would be an example how the magic function __toString() works:

$variables['fields']['title'] = Drupal\Core\Render\Markup::create($variables['fields']['title'] . '!!!');