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The objective of this study was to investigate the functional form of the relationship between diet composition (dietary crude protein [CP] and neutral detergent fiber [NDF]) and amount of substrate (fermenter dry matter intake [DMI]) with microbial fermentation end products in a dual-flow continuous culture system. A meta-analysis was performed using data from 75 studies. To derive the linear models, the MIXED procedure was used, and for nonlinear models, the NLMIXED procedure was used. Significance levels to fit the model assumed for fixed and random effects were P ≤ 0.05. Independent variables were dietary NDF, CP, and fermenter DMI, whereas dependent variables were total volatile fatty acids (VFA) concentration; molar proportions of acetate, propionate, and butyrate; true ruminal digestibilities of organic matter (OM), CP, and NDF; ammonia nitrogen (NH3–N) concentration and flows of NH3–N; non-ammonia nitrogen; bacterial-N; dietary-N; and efficiency of microbial protein synthesis (EMPS). Ruminal digestibilities of OM, NDF, and CP decreased as fermenter DMI increased (P < 0.04). Dietary NDF and CP digestibilities were quadratically associated (P < 0.01). Total VFA linearly increased as DMI increased (P < 0.01), exponentially decreased as dietary NDF increased (P < 0.01), and was quadratically associated with dietary CP (P < 0.01), in which total VFA concentration was maximized at 18% dietary CP. Molar proportion of acetate exponentially increased (P < 0.01) as dietary NDF increased. Molar proportion of propionate linearly increased and exponentially decreased as DMI and dietary NDF increased, respectively (P < 0.01). Bacterial-N quadratically increased and dietary-N exponentially increased as DMI increased (P < 0.01). Flows of bacterial-N and dietary-N linearly decreased as dietary NDF increased (P < 0.02), and dietary-N flow was maximized at 18% CP. The EMPS linearly increased as dietary CP increased (P < 0.02) and was not affected by DMI or dietary NDF (P > 0.05). In summary, increasing fermenter DMI increased total VFA concentration and molar proportion of propionate, whereas, dietary NDF increased the molar proportion of acetate. Dietary CP increased bacterial-N flow and was positively associated with NH3–N concentration. Overall, the analysis of this dataset demonstrates evidences that the dual-flow continuous culture system provides valuable estimates of ruminal digestibility, VFA concentration, and nitrogen metabolism.