Due to its cost effectiveness and sustainability, anaerobic digestion (AD) has become a widely adopted technology for wastewater treatment as well as bioenergy production. However, knowledge of the structure and the dynamics of microbial communities involved in this process is essential to improve system performance and optimize system operations. Here we investigated the performance and the dynamics of the microbial communities in intermediate (10ppt) and high (35ppt and 30ppt) salinity laboratory scale multi-stage anaerobic reactors fed with marine macroalgae (Sargassum spp.) over 180 performance days by using barcoded 454 pyrosequencing of 16S rRNA genes. The outcome of this survey may be summarized in five major findings: (1) The intermediate salinity bioreactor is significantly more efficient in terms of biogas production than the high salinity bioreactor; (2) The alpha diversity was found to decrease over time in response to the adaptation of the microbial communities to different environmental factors; (3) Fermentative Bacteroidetes and Firmicutes were the predominant and the most stable microbial groups in the mature anaerobic reactors; (4) The PCoA reveals significant Beta diversity attributed to reactor salinity (R= 0.54, p = 0.002), which is an indicator that salt concentration is a strong ecological factor that shapes the biogas reactor microbial communities, (5) No significant partition of microbial communities was observed in either the 2L two-­‐stage bioreactors, or the 15L three-­‐compartment reactor systems; and (6) Finally, in spite of the crucial role of methanogenic Archaea for biogas production, they are present as a remarkably small fraction (1- 2%) of the mature bioreactor microbial communities. The characterization of the biogas produced and additional meta-metabolomics studies are suggested in order to better understand the microbial community functions in these systems.