The large amount of protein-rich organic waste generated annually is an extremely valuable substrate of anaerobic digestion. Although free ammonia (FAN, NH3) and ammonium (NH4+) are so far the most widely acknowledged inhibitors affecting operational stability, the detailed inhibition mechanisms in the processing of,protein-rich material remain unclear. The present study aimed to determine the single or synergistic effects initiated by the anaerobic degradation of highly loaded protein, in hopes of understanding how a microbial ecosystem responds to altered environmental conditions such as changes in NH3, NH4+, acetate, volatile fatty acids (VFA), pH, and alkalinity. A high solid anaerobic digester with protein-rich organic wastes was operated semi-continuously which endured a complete stable-inhibited-recovered cycle during the whole operation of 125 days. The kinetics of methanogenesis from acetic acid (HAc) in the system was analyzed and modelled to clarify the physiologic properties of methanogens under inhibition conditions. The community dynamics of archaea and bacteria during the operation were monitored by 16S rRNA pyrosequencing following the QIIME pipeline, and nonmetric multidimensional scaling (NMDS) analysis was conducted to ordinate the ecological community with kinetics fitting parameters. As a result, the inhibition and recovery in methane production are intrinsically attributed to the changes in total ammonium nitrogen (TAN), alkalinity, and VFA (acetate), because these factors dictate the changes in a bacterial community, triggering the shift in the methanogenic pathway from acetoclastic to hydrogenotrophic methanogenesis. The more sensitive responses from the bacterial community than the methanogenic community also indicated that specific bacterial species, such as T78 (before day 38), RFN20 (days 40-56), Tepidimicrobium (days 60-66), and unclassified Clostridia (after day 70), might be better biomarkers of digester performance. (C) 2017 Elsevier B.V. All rights reserved.