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The potential of extrusion-cooking to change the physicochemical characteristics of wheat bran, increase its nutritional value and decrease its recalcitrance towards fermentation was investigated in this study. The conditions in a twin-screw extruder were varied by changing screw configuration, moisture content and barrel temperature. The former was not previously investigated in studies on bran extrusion. Extrusion-cooking resulted in an increased water-holding capacity and extract viscosity of bran, suggesting shear-induced structure degradation and structure loosening due to steam explosion at the extruder outlet. Modelling showed that the extent of these modifications mainly correlates with the amount of specific mechanical energy (SME) input, which increases with an increasing number of work sections in the screw configuration and a decreasing moisture content and barrel temperature. Extrusion led to solubilisation of arabinoxylan and ferulic acid. Moreover, it led to starch melting and phytate degradation. Upon fermentation of the most modified sample using a human faecal inoculum, small numeric pH decreases and short-chain fatty acid production increases were observed compared to the control bran, while protein fermentation was decreased. Overall, extrusion-cooking can improve the nutrition-related properties of wheat bran, making it an interesting technique for the modification of bran before further use or consumption as an extruded end product.