Gut Microbiota-Derived SCFAs Modulated by Different Structures of Marine Algal Oligosaccharides Alleviate Colitis Through PPARγ Signaling Activation

Background: Marine algal oligosaccharide (MAO) molecular structural characteristics are closely related to their bioactivity. However, an understanding of the specific relationships between MAO molecular structure (including polymerization degree [DP] and sulfate groups) and bioactivity is lacking. Methods: In this work, laboratory-prepared DP4 and DP8 MAOs, including agar- (AOs) and κ-, ι-, and λ-carrageenan-oligosaccharides (COs), were examined for their anti-inflammatory activity in RAW264.7 macrophages and therapeutic effect on colitis in mice; additionally, the potential mechanisms involved were explored. Results: The results showed that CO (ι- and λ-COs) anti-inflammatory activity was higher than that of AOs and was positively correlated with sulfate group content. MAOs with different structures all alleviated colitis symptoms; those with higher sulfate group content and DP showed excellent therapeutic efficacy. MAOs modulated gut microbiota and promoted the enrichment of microbiota-derived short-chain fatty acid production (butyrate), which potentially induced PPARγ signaling and contributed to the impacts of MAOs on mucosal homeostasis restoration. Conclusions: Therefore, MAOs with higher sulfate content and DP showed improved therapeutic efficacy compared with those with lower contents, which involved higher SCFA production.