Gelidium Bioactives in Gut and Skin Homeostasis: Mechanisms, Microbiota Modulation, and the Gut-Skin Axis

The marine ecosystem remains an unparalleled reservoir of structurally unique macromolecular biomolecules with diverse pharmaceutical applications. Among red macroalgae (Rhodophyta), the genus Gelidium Lamouroux is economically renowned as a primary industrial source of agar. Beyond its traditional hydrocolloid utility, recent molecular evidence reveals that Gelidium biomass possesses a dense matrix of non-digestible sulfated galactans, low-molecular-weight agaro-oligosaccharides, marine bromophenols, polyphenols, and mycosporine-like amino acids that have shown promising biological activities and therapeutic potential in preclinical models. Utilizing advanced green depolymerization and extraction technologies-including enzyme-assisted, ultrasound-assisted, and subcritical water extraction-these structural polysaccharides and specialized secondary metabolites can be efficiently isolated while optimizing yields and preserving bioactive functional integrity. This review comprehensively synthesizes the dual-target therapeutic modalities of Gelidium bioactives, focusing on their prebiotic modulation of the gastrointestinal microbiota and their protective effects on cutaneous tissues. In the gastrointestinal tract, Gelidium polysaccharides resist upper digestive enzymatic hydrolysis, serving as selective fermentable substrates that significantly enrich beneficial saccharolytic taxa while suppressing opportunistic pathobionts. This microbial fermentation accelerates the synthesis of short-chain fatty acids; based on established epithelial models, these organic acids provide a mechanistic rationale for upregulating epithelial tight junction proteins (zonula occludens-1, occludin, and claudin-1), theoretically supporting intestinal barrier integrity and mitigating systemic endotoxemia. Concurrently, in cutaneous tissues, selected Gelidium-derived fractions have been reported to modulate matrix metalloproteinases, including matrix metalloproteinase-1, matrix metalloproteinase-2, and matrix metalloproteinase-9, scavenge reactive oxygen species via nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 pathway activation, and modulate oxidative and melanogenic pathways to support cutaneous homeostasis. Finally, we establish the theoretical framework of the gut-skin axis as an experimentally supported systemic conduit through which Gelidium-mediated intestinal homeostasis attenuates cutaneous inflammation, photoaging, and barrier disruption. We further address current bioavailability limitations, standardization hurdles, and future clinical trajectories required to translate Gelidium biomass into functional nutricosmetics and marine therapeutics.