The fluctuation of environmental conditions drives the structure of microbial communities in estuaries, highly dynamic ecosystems. Microorganisms inhabiting estuarine sediments play a key role in ecosystem functioning. They are well adapted to the changing conditions, also threatened by the presence of pollutants. In order to determine the environmental characteristics driving the organization of the microbial assemblages, we conducted a seasonal survey along the Adour Estuary (Bay of Biscay, France) using 16S rRNA gene Illumina sequencing. Microbial diversity data were combined with a set of chemical analyses targeting metals and pharmaceuticals. Microbial communities were largely dominated by Proteobacteria (41 %) and Bacteroidota (32 %), showing a strong organization according to season, with an important shift in winter. The composition of microbial communities showed spatial distribution according to three main areas (upstream, middle, and downstream estuary) revealing the influence of the Adour River. Further analyses indicated that the microbial community was influenced by biogeochemical parameters (Corg/Norg and 13C) and micropollutants, including metals (As, Cu, Mn, Sn, Ti, and Zn) and pharmaceuticals (norfloxacin, oxolinic acid and trimethoprim). Network analysis revealed specific modules, organized around keystone taxa, linked to a pollutant type, providing information of paramount importance to understand the microbial ecology in estuarine ecosystems.