We present an ab initio study of inclusive semileptonic decays of heavy mesons from lattice QCD. Our approach is based on a recently proposed method, that allows one to address the study of these decays from the analysis of smeared spectral functions extracted from four-point correlators on the lattice, where the smearing is defined in terms of the phase-space integration relevant to the inclusive decays. We present results obtained from gauge-field ensembles from the JLQCD and ETM collaborations, and discuss their relation with theoretical predictions from the operator-product expansion.