This narrative review highlights the complexities of the gut microbiome and health-promoting properties of prebiotic xylans metabolized by the gut microbiome. In animal husbandry, prebiotic xylans aid in the maintenance of a healthy gut microbiome. This prevents the colonization of the gut by pathogenic organisms obviating the need for dietary antibiotic supplementation, a practice which has been used to maintain animal productivity but which has led to the emergence of antibiotic resistant bacteria that are passed up the food chain to humans. Seaweed xylan-based animal foodstuffs have been developed to eliminate ruminant green-house gas emissions by gut methanogens in ruminant animals, contributing to atmospheric pollution. Biotransformation of pentosan polysulfate by the gut microbiome converts this semi-synthetic sulfated disease-modifying anti-osteoarthritic heparinoid drug to a prebiotic metabolite that promotes gut health, further extending the therapeutic profile and utility of this therapeutic molecule. Xylans are prominent dietary cereal components of the human diet which travel through the gastrointestinal tract as non-digested dietary fibre since the human genome does not contain xylanolytic enzymes. The gut microbiota however digest xylans as a food source. Xylo-oligosaccharides generated in this digestive process have prebiotic health-promoting properties. Engineered commensal probiotic bacteria also have been developed which have been engineered to produce growth factors and other bioactive factors. A xylan protein induction system controls the secretion of these compounds by the commensal bacteria which can promote gut health or, if these prebiotic compounds are transported by the vagal nervous system, may also regulate the health of linked organ systems via the gut-brain, gut-lung and gut-stomach axes. Dietary xylans are thus emerging therapeutic compounds warranting further study in novel disease prevention protocols.