Bacteroides finegoldii and Parabacteroides goldsteinii Mediate Fucoidan-Induced Attenuation of Intestinal Inflammation in Mice Through Betaine- and Spermidine-Related Pathways

Fucoidan improves host health by enriching beneficial taxa such as <i>Bacteroides</i> and <i>Parabacteroides</i>, yet the underlying mechanisms remain unclear. This study validated the association between these two genera and fucoidan-mediated mitigation of intestinal inflammation in mice. Subsequently, the effects of <i>Parabacteroides goldsteinii</i> and <i>Bacteroides finegoldii</i> were evaluated in colitis mice, and the contributions of microbiota-associated metabolites spermidine and betaine were investigated in vitro. Both strains reduced IL-6 (32-36%), TNF-α (30-37%), and IL-1β (40-45%) levels and increased levels of catalase (25-35%) and glutathione peroxidase (31-45%) in the colon. Mechanically, these strains suppressed activation of the NF-κB and MAPK pathways and preserved tight junction integrity by inhibiting myosin light chain kinase activation. These effects were associated with alterations of gut microbiota, characterized by decreased Proteobacteria and increased Bacteroidota, resulting in increased betaine (45-60%) and spermidine (90-112%). In vitro, betaine and spermidine alleviated LPS-induced inflammation and oxidative damage by regulating macrophage polarization. These results suggest that <i>Bacteroides</i> and <i>Parabacteroides</i> contribute to fucoidan-induced improvement of host health through betaine- and spermidine-related pathways. Future studies should clarify the origins of key metabolites and validate their causality and translational relevance using approaches such as fecal microbiota transplantation, metabolite tracing, and human-relevant systems.