In this paper, we obtain bounds on the Wilson loop expectations in 4D U(1) lattice gauge theory, which quantify the effect of topological defects. In the case of a Villain interaction, by extending the non-perturbative technique introduced in [24], we obtain the following estimate for a large loop gamma at low temperatures: |& lang;W-gamma & rang;(beta)| <= exp ( - C-GFF/2 beta(1 + C beta e(-2 pi 2 beta))(|gamma|+o(|gamma|))). Our result is in line with recent works [4, 9, 13, 15] which analyze the case where the gauge group is discrete. In the present case where the gauge group is continuous and Abelian, the fluctuations of the gauge field decouple into a Gaussian part, related to the so-called free electromagnetic wave [11, 23], and a gas of topological defects. As such, our work gives new quantitative bounds on the fluctuations of the latter which complement the works by Guth and Frolich-Spencer [17, 27]. Finally, we improve, also in a non-perturbative way, the correction term from e(-2 pi 2 beta) to e(-pi 2 beta) in the case of the free-energy of the system. This provides a matching lower-bound with the prediction of Guth [27] based on renormalization group techniques.