Brachyspira hyodysenteriae is an etiological agent of swine dysentery (SD). Diet fermentability plays a role in development of SD, but the mechanism(s) of action are largely unknown. Thus, this study aimed to determine whether replacing lowly fermentable fiber with highly fermentable fiber would mitigate a 42 d B. hyodysenteriae challenge. Thirty-nine barrows were allocated to dietary treatment groups: (1) 20% corn distillers dried grain with solubles (DDGS), 0% beet pulp (BP) or resistant starch (RS; lowly fermentable fiber (LFF)); (2) 10% DDGS, 5% BP, 5% RS (medium fermentable fiber (MFF)); and (3) 0% DDGS, 10% BP, 10% RS (highly fermentable fiber (HFF)). On day post inoculation 0, pigs were inoculated with B. hyodysenteriae. Overall, 85% LFF pigs developed clinical SD, 46% of MFF pigs developed SD, and 15% of HFF pigs developed SD (p < 0.05). Overall average daily gain (ADG) differed among all treatments (p < 0.001), with LFF pigs having the lowest ADG. For HFF pigs, ADG was 37% greater than LFF pigs (p < 0.001) and 19% greater than MFF pigs (p = 0.037). The LFF diet had greater relative abundance of Shuttleworthia and Ruminococcus torques. Further, microbiota of pigs that developed SD had enriched Prevotellaceae. Collectively, replacing DDGS with highly fermentable fiber reduced clinical SD, improved performance, and modulated fecal microbiota during B. hyodysenteriae challenge.