Seabird colonies produce large amounts of guano that can enter coastal waters providing soluble bioavailable substrates for microbial plankton communities, but their role in marine ecosystem functioning remains poorly understood. A series of guano water soluble fraction (WSF) addition experiments was performed in microcosms with different natural microbial communities collected in surface waters from the Ria de Vigo (NW Spain) in spring, summer, and winter to test whether gull guano stimulated phytoplankton and bacterial growth, caused changes in taxonomic composition, and altered phytoplankton-bacteria interactions. Two concentrations of the WSF of guano were added to microbial communities, which were incubated with or without antibiotics (to block bacterial activity). Chlorophyll a (Chl a) concentration and bacterial abundance significantly increased after additions independently of the initial ambient nutrient concentrations. Importantly, our study demonstrates, for the first time, that the addition of guano altered the phytoplankton-bacteria interaction from neutral (i.e., phytoplankton growth did not affected by bacterial activity) to positive (i.e., phytoplankton growth was stimulated by bacterial activity) in the low-nutrient environment occurring in spring. By contrast, in autumn, when environmental nutrient concentrations were high, these interactions changed from positive to neutral after guano additions, suggesting the presence of some secondary metabolite in the guano that is needed for phytoplankton growth, which would otherwise be supplied by bacteria.