A first insight on the interactions between bacteria isolated from monospecific cultures of the marine diatom Haslea ostrearia and this microalgae is described in this work. From 28 bacterial isolates, the maximal growth rate and the maximal cell concentration were on average 58% and 27% higher (max. 67% for isolate B22). Isolates B5, B10 (both Saccharospirillum sp.) and B22 (Rhodobacter sp.) were the most efficient. The geographical origin of H. ostrearia from which bacteria were isolated had no impact on the algal growth performances, and a given bacterial isolate led to the same algal growth irrespective of the geographical origin of H. ostrearia. To explain the results obtained, a comprehensive integrative strategy was conducted that analyzed the variations in the thousands of metabolites present in our culture extracts. Beyond a holistic view in which all organic substances of natural origin derived from the metabolism of a living organism were analyzed, we focussed on metabolites specific to each partner of the bacteria-H. ostrearia co-cultures, and relating to a particular biological function. To this end, a high throughput analytical technique, mass spectrometry was used, along with uni- and multivariate association statistical methods. Metabolic fingerprinting (untargeted approach) enabled compounds specific to each association to be identified, especially those concerning the positive bacterial effect on the growth of H. ostrearia.