Molecular and microbial signatures predictive of prebiotic action of neoagarotetraose in a dextran sulfate sodium induced murine colitis model

Neoagarotetraose (NT), a hydrolytic product of agar by beta agarase, is known to possess bioactive properties. However, the mechanisms via which NT alleviates intestinal inflammation remain elusive. In this study, a dextran sulfate sodium (DSS) induced murine model was developed to evaluate the effect of NT on gut microbiome and microbial metabolism using 16S rRNA gene sequencing and untargeted metabolomics. Our data demonstrate that NT ingestion improved gut integrity, ulcers and inflammation scores. NT partially restored DSS induced gut dysbiosis. NT reversed the abundance of Proteobacteria from an elevated level induced by DSS and significantly increased the abundance of Verrucomicrobia. Further, NT significantly increased the abundance of Akkermansia and Lactobacillus and concomitantly decreased that of Sutterella, which were among the important features identified by random forests analysis contributing to classification accuracy for NT supplementation. A microbial signature consisting of Adlercreutzia (denominator) and Turicibacter (Numerator) predicted the NT supplementation status. Moreover, NT significantly modulated multiple gut metabolites, particularly those related to histidine, polyamine and tocopherol metabolism. Together, our findings provided novel insights into the mechanisms by which NT modulated the gut microbiome and metabolome and should facilitate NT as a potent prebiotic for colitis management.