Full-scale anaerobic digesters' performance is regulated by modifying their operational conditions, but little is known about how these modifications affect their microbiome. In this work, we monitored two originally mesophilic (35 degrees C) full-scale anaerobic digesters during 476 days. One digester was submitted to sub-mesophilic (25 degrees C) conditions between days 123 and 373. We characterized the effect of temperature modification using a multi-omics (metataxonomics, metagenomics, and metabolomics) approach. The metataxonomics and metagenomics results revealed that the lower temperature allowed a substantial increase of the sub-dominant bacterial population, destabilizing the microbial community equilibrium and reducing the biogas production. After restoring the initial mesophilic temperature, the bacterial community manifested resilience in terms of microbial structure and functional activity. The metabolomic signature of the sub-mesophilic acclimation was characterized by a rise of amino acids and short peptides, suggesting a protein degradation activity not directed towards biogas production.