My great grandfather, Henry E. Kerley's sister, LuCinda Kerley, married a Fielding Frank Middleton b 1859. Census records show he was born in Kentucky to Fielding Middleton b. 1805 in Kentucky. His father may have been the brother of your John Middleton.
Fielding Frank Middleton and LuCinda Kerley Middleton lived in the Maries/Gasconade County area of Missouri. I know they had at least one child a son,and a daughter.
Hope this helps in your search.