Marine Polysaccharides Modulating the Gut Microbiota-Immune Axis in Digestive Tract Tumors: An Update

Digestive tract tumors represent a predominant contributor to the global public health burden, with conventional therapeutic modalities experiencing inherent limitations and immunotherapy being impeded by the immunosuppressive property and heterogeneity of the tumor microenvironment (TME). This makes the gut microbiota-immune axis a promising therapeutic target. Marine polysaccharides, endowed with distinctive structural characteristics, exhibit potential in the modulation of this regulatory axis, yet their structure-activity relationships (SARs) and the intrinsic limitations in delivery efficiency remain largely unelucidated. In this review, we systematically synthesized the latest research advances pertaining to the modulation of the gut microbiota-immune axis by marine polysaccharides in digestive tract tumors, in accordance with the logical framework of polysaccharide structure, flora regulation, immune activation, tumor inhibition, and delivery optimization. We elaborated on the bidirectional crosstalk between the gut microbiota and the immune axis during tumorigenesis, as well as the regulatory effects and core underlying mechanisms of marine polysaccharides derived from algal, animal and microbial sources on this axis, including targeted floral regulation, microbiota-mediated immune activation, and direct/indirect tumor suppression. We also analyzed the key structural determinants and structural modification strategies of marine polysaccharides, alongside the development of nanodelivery systems for the improvement of their oral bioavailability. Furthermore, we identified critical existing research gaps, such as the ambiguous SARs and poor oral bioavailability of marine polysaccharides, and propose the integration of multi-omics analysis, synthetic biology technology and advanced nanodelivery strategies as the core future research directions in this field. Collectively, marine polysaccharides hold tremendous promise as novel therapeutic agents for digestive tract tumors, and interdisciplinary collaboration is regarded as indispensable for their successful clinical translation and translational application.