Gatekeeping Dietary Fiber: The Role of Carbohydrate-Binding Modules in the Human Gut.

Carbohydrate-binding modules (CBMs) are widely recognized as accessory domains that enhance polysaccharide hydrolysis by carbohydrate-active enzymes. Using genomic surveys and ecological mapping across the human gastrointestinal tract, we outline three previously unrecognized principles of CBM distribution. First, CBM repertoires show substrate-axis specialization consistent with the carbohydrate targets of different microbial groups. Second, patterning emerges along the oral-ileal-colonic axis, reflecting spatial gradients in substrate availability and microbial niches. Third, CBM compositions encode ecological strategy signatures, distinguishing between primary degraders, trophic intermediates, and mucosal specialists. Integrating these insights, we propose a CBM-driven digestive pipeline linking substrate recognition and microbial attachment to primary hydrolysis, cross-feeding networks, and short-chain fatty acid production. This pipeline links CBM-mediated carbohydrate processing to host physiological outcomes, including gut barrier integrity, metabolic homeostasis, and excretion. Together, these findings highlight CBMs as important contributors to diet-microbe-host metabolic interactions and suggest that CBM profiles may help inform how dietary fibers are processed and fermented into downstream metabolites.