Rational bioengineering of polysaccharide in designing of microbiome modulation.

Targeted modulation of the gut microbiome offers significant promise for preventing and treating diverse diseases; yet, enhancing the efficacy of these interventions remains challenging. Polysaccharides have emerged as potent microbiome modulators, functioning as prebiotics that selectively promote beneficial bacterial growth and metabolite production. Their resistance to gastric degradation and selective intestinal fermentation enhance the precision of microbiome modulation while facilitating direct immunomodulatory interactions via pattern recognition receptor engagement on gut immune cells. Despite their high potential, polysaccharide-based microbiome modulators remain underrecognized. Advances in polysaccharide bioengineering now allow rational design of structure-function relationships, enabling targeted control of microbial communities and host immune responses. This review highlights these developments and applications, providing a timely perspective on next-generation microbiome-targeted strategies.