Background/Objectives: Alginate and its oligosaccharides (AOS) are widely used in the food industry all over the world. However, how they are fermented by the human gut microbiota has not been fully elucidated. Here, we aim to explore the structure–property relationships of the fermentation of these carbohydrates by the human gut microbiota. Methods: High-performance liquid chromatography, 16S rRNA gene amplicon high-throughput sequencing, whole genome sequencing, and metabolome analysis were used to study the fermentation of alginate and AOS by the human gut microbiota. Results and Conclusions: Low-molecular-weight alginate and AOS were more fermentable than alginate. Moreover, fermentation of AOS with a molecular weight (Mw) of 0.8 kDa produced higher amounts of acetate and butyrate than that with a Mw of 0.3 kDa. B. xylanisolvens was a keystone species responsible for the fermentation. Additionally, each B. xylanisolvens strain was characterized with a unique capability for AOS fermentation. Specifically, B. xylanisolvens P19-10, a bacterium isolated from healthy human colon, exhibited the best fermentation capacity. Genomic analysis suggested that B. xylanisolvens P19-10 was armed with a plethora of carbohydrate-active enzymes. Additionally, the polysaccharide lyase family 6_1 was identified as a candidate enzyme responsible for the utilization of AOS. Moreover, fermentation of AOS by B. xylanisolvens P19-10 was associated with significant changes in bacterial metabolites and metabolic pathways. Future perspectives: Our study provides novel mechanistic insights into the fermentation of alginate and AOS by human gut microbiota, which has applications for the development of new carbohydrate-based nutraceuticals and foods.

Oligoguluronate lithium (OGLi) was prepared for the purpose of enhancing the anti-ulcerative colitis (UC) activities of OG, in which lithium (Li⁺) is coupled with the C6-carboxyl of G residue. The therapeutic effects of OGLi on dextran sulfate (DSS)-induced UC mice were investigated, and oligoguluronate sodium (OGNa) and lithium carbonate (LC) were used as contrasts. The effects of OGLi, OGNa and LC on the treatment of UC mice were studied by monitoring body weight change and evaluating colon length, the disease activity index (DAI), histopathological examination and gut microbiota regulation. The results showed that compared with OGNa and LC, OGLi significantly reduced the clinical symptoms and histopathological changes associated with UC in the acute model. It was worth noting that OGLi significantly changed the gut microbiota characteristics of the DSS-treated mice and corrected the typical dysbacteriosis of DSS-induced UC. This intervention resulted in increasing the abundance of norank_f_Muribaculaceae and Ileibacterium spp. while reducing the levels of Escherichia-Shigella spp. and Romboutsia spp. The OGLi could significantly increase the diversity of intestinal microorganisms in the short term. All of these discoveries demonstrate that lithium collaboratively enhances the anti-UC efficacy of OG, which will help to create OG-based drugs for the treatment of UC.

Alginate oligosaccharides (AOS) are attractive candidates for prebiotic development, yet how oligosaccharide structure and baseline microbial community composition interact to shape fermentation remains an open question. In this study, we stratified fecal microbiota from healthy donors into operational genus-predominance groups (Bifidobacterium, Bacteroides, Faecalibacterium, or Blautia) and selected representative samples for in vitro fermentation of six structurally distinct AOS preparations (SAOS-1, SAOS-2, OAOS, UAOS, SMOS, and SGOS). Substrate consumption, short-chain fatty acid (SCFA) production, and shifts in microbial community structure were profiled. The six preparations differed in structural type, number-average molecular weight, and average degree of polymerization. Among them, SAOS-1 exhibited the most consistent utilization across all four groups and yielded the highest total SCFA production. SAOS-1 fermentation also attenuated inter-group community divergence and enriched several beneficial or functionally relevant taxa, including Bacteroides and Faecalibacterium. Interestingly, the magnitude and direction of microbial responses remained enterotype-dependent, with the Bacteroides-predominant group assembling the most complex fermentative consortium. These findings demonstrate that AOS structure and baseline microbial ecology jointly dictate fermentation outcomes, positioning SAOS-1 as a strong candidate for precision prebiotic development. This structure–community interaction paradigm provides a rational basis for the targeted deployment of marine oligosaccharides in personalized gut health strategies.