Fucoidan improves glucose and lipid metabolism in T2DM rats through the gut-liver axis

Authors:
  • YLYaping Liu
    Yaping Liu
  • XTXingyue Tao
    Xingyue Tao
  • XWXiaoxiao Wang
    Xiaoxiao Wang
  • ZSZhanyi Sun
    Zhanyi Sun
  • PSPeili Shen
    Peili Shen
  • WLWenjie Li
    Wenjie Li
  • PLPeifei Li
    Peifei Li

Abstract
Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and gut microbiota dysbiosis, represents a significant global health challenge. Fucoidan, a sulfated polysaccharide derived from brown algae, exhibits potential antidiabetic properties; however, its limited systemic bioavailability due to macromolecular structure thereby suggesting the involvement of microbiota-mediated mechanisms. This study investigated the contribution of fucoidan-induced gut microbiota alterations to improvements in glucolipid metabolism and elucidated the underlying molecular mechanisms in T2DM rats. Results demonstrated that administration of fucoidan (200 mg/kg) to T2DM rats remodeled the gut microbiota, enhanced the abundance of beneficial bacteria, improved intestinal barrier integrity, and reduced the production and translocation of lipopolysaccharide (LPS), consequently inhibiting the hepatic TLR4/NF-κB signaling pathway and alleviating inflammatory stress and its suppression on insulin signaling. This inflammatory amelioration further promoted the activation of both the insulin-sensitizing PI3K/AKT pathway and the energy-sensing AMPK/SIRT1 pathway, enhancing glucose uptake and lipid oxidation while suppressing gluconeogenesis and lipogenesis. Crucially, fecal microbiota transplantation (FMT) from fucoidan-treated donors recapitulated these metabolic improvements in recipient T2DM rats, confirming the causal role of the reshaped microbiota and its function. Specifically, FMT recipients exhibited restored intestinal barrier integrity, suppressed TLR4/NF-κB-mediated inflammation, and significantly improved hepatic glucose/lipid metabolism and insulin signaling. Collectively, these findings delineate a clear gut-liver axis mechanism: fucoidan alleviates T2DM by remodeling gut microbiota composition and function, which enhances intestinal barrier integrity, attenuates inflammation, and restores hepatic metabolic homeostasis via modulation of the PI3K/AKT and AMPK/SIRT1 pathways, establishing its therapeutic promise as a microbiota-targeting functional food for T2DM management.