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Abstract: Understanding how human-induced management interacts with and affects the structure and functioning of large estuarine ecosystems is a major research challenge. In West Africa, human intervention on the Senegal River Estuary was intended to reduce the impact of major flooding by opening a new mouth in October 2003, 25 km to the north of the existing mouth. This study describes the effects of the new environmental conditions on the physical and biochemical characteristics of the water column and on microbial communities (bacteria, phytoplankton by size class and heterotrophic nanoflagellates (HNF)) in comparison with the situation in 2002. In 2006, seventeen stations were sampled, during both neap and spring tides, at a depth of 0.5 m along a salinity gradient from freshwater to marine conditions. Inorganic nutrient levels were often low but there were high levels of chlorophyll a in the estuarine area (mean of 13.7–20.7 μg L−1 in spring and neap tide conditions, respectively) producing a eutrophic status in this estuary. Average HNF abundances were lower (mean of 108 and 174 cells l−1 during neap and spring tides, respectively) compared to the situation in 2002 (mean between 2.5 and 6.7 × 104 cells l−1). Three biological indicators for assessing environmental changes are discussed: ratio of bacteria to heterotrophic flagellate abundances, ratio of picophytoplankton to nanophytoplankton, and the density of thermo-tolerant coliforms (TTC) and faecal streptococci. It is demonstrated that man-made alteration of the hydrologic regime can modify the microbial community structure and cause the health status of the estuary to deteriorate. [Copyright &y& Elsevier]