Client Access/400 is the easiest way to go, which is basically an ODBC driver. IBM also has an ADODB component that they call (or used to call) "Lightning".
I have only had experience with Client Access on Windows/NT, so you'll have to investigate what ODBC drivers they have for other platforms if you require it.
What you want to do is install Client Access on your web or app server and configure a DSN as you would for any other ODBC driver.
Hope this helps.
Hasib