I'm running a fairly large WP multi site installation and every time I run "Update Network" (where it goes through each blog's db and does stuff) it breaks the sites' permalinks.
If I do the standard "go to each blog" and hit "Save" under the permalinks settings, everything works again but it's not practical to do that for ~50 sites (and growing) every time I update the network. There shouldn't be any issues with my mod_rewrite rules.
I'm thinking it may be a plugin, but how would I narrow it down? I can't just disable all of the plugins on my site... most of them are network disabled anyway and enabled one-by-one on each site based on its needs.