To improve the resistance of an anaerobic microbiota to phenol, a pollutant commonly recovered in bioprocesses treating organic waste, an acclimation strategy was applied to a lab-scale semi-continuous bioreactor digesting cellulose. It consisted in a regular step-wise adaptation of the microbiota to stressful condition, namely phenol level. After stable functioning without inhibitor (100 days), 3 successive adaptation episodes were applied (450 days). They resulted in a progressive minimization of the inhibitory effect of phenol on degradation performances and developed microbiota resistance: total inhibition threshold increased from 895 to 1942 mg/L of phenol. 16S sequencing revealed that Archaea adapted through the selection of the most resistant OTU from Methanobacterium genus while Bacteria adaptation was explained by an important plasticity especially within Clostridiales and Bacteroidales orders. Collectively, 16S analyses suggested that the phenol tolerant microorganisms were generally present in the original inoculum, but not initially dominant. To go further in the understanding of the adaptation mechanisms that enabled the increased resistance of the microbiota, metatranscriptomics analyses were realized on four samples from the different episodes of the experiment (without inhibitor/adaptation). They revealed that the expression of several functions related to carbohydrates metabolism (especially sugars and alcohol) and aromatic compounds metabolism was decreased with increasing phenol level, whereas functions related to heat stress were newly expressed. To complete the study, metabolomics analyses were performed on a high-resolution mass spectrometer (LTQ-Orbitrap XL) by direct infusion. Data were combined and analysed by independent component analyses and common components and specific weights analyses.