Gauge theories are considered to live on $G$-principal bundles $P$ over the spacetime $\Sigma$. For convenience, the usual text often either compactify $\Sigma$ or assume it is already compact.
An instanton is now a "false vacuum" of the theory - a local minimum of the action functional. In four dimensions, instantons are the (anti-)self-dual configurations with $\star F = \pm F$, and the Yang-Mills action then is just the integral over $\mathrm{Tr}(F \wedge F)$, which is the characteristic class of the bundle, also called its Chern class, which are connected through Chern-Weil theory. This class is a topological invariant of the principal bundle associated to a field configuration.
As this math.SE post indicates, the isomorphism classes of bundles over a manifold are in bijection with its first Cech cohomology, which, for smooth manifolds, agrees with the usual other cohomology theories if $G$ is abelian. The question is now twofold:
If $G = \mathrm{U}(1)$, does the existence of instanton solutions imply non-trivial first ordinary (singular, DeRham, whatever) cohomology of spacetime? Or is it rather the case that the instanton/non-trivial bundle configuration only indicates that the gauge theory only holds on the spacetime with points (or possibly more) removed, indicating the presence of magnetic monopoles at these points rather than anything about spacetime?
If $G$ is non-abelian, does the existence of instanton solutions, and hence the non-vanishing of the "non-abelian Cech cohomology" imply anything about the topological structure of spacetime? Perhaps something about the non-abelian homotopy groups rather than the abelian homology? Or, again, does this indicate a non-abelian analogon of monopoles?