This song is often used in square-dancing, so I’ve always assumed that “skip to my Lou” might be an abbreviation for “skip to the left” or some such. Allemande left and do-si-do talk.
The part about the flies in the buttermilk bothers me, so I would rather not think about these lyrics in any depth.
The lyrics to Skip to my Lou were written in 1843 by Daniel Decatur Emmett. This site claims the tune is from an “18th century British country dance.” I found nothing on who ‘lou’ is, but Emmet did marry one Mary Louise Bird in 1879.
Emmet also wrote such hits as (wish I was in) Dixie, Old Dan Tucker, Turkey in the Straw, and The Blue Tail Fly.