Sialylated IgG mediates the colonization of Bifidobacterium bifidum through the “FcRn-Sialylated IgG-SiaBb2” axis, alleviating high-fructose diet-induced neuroinflammation in mice by activating the cAMP/PKA signaling pathway

Abstract

Bifidobacterium can alleviate neuroinflammation but is hindered by physiological barriers, such as pH and oxygen levels, limiting its long-term colonization in the gut. Therefore, this study developed a W/O oleogel emulsion formulated with β-sitosterol and glyceryl monostearate (GMS) effectively stabilized Sialylated IgG (SIgG) and Bifidobacterium bifidum under gastric conditions while enabling the targeted release in intestine. Furthermore, SIgG released from the oleogel emulsion facilitated the colonization of B. bifidum in the gut by mediating interactions between the surface protein SiaBb2 of B. bifidum and the FcRn receptor on intestinal epithelial cells. This colonization significantly enhanced intestinal barrier integrity, suppressed systemic and neuroinflammatory cytokines, and activated the cAMP/PKA signaling pathway, thereby alleviating neuroinflammation and neuronal damage in the model of male C57BL/6J mice induced by a high-fructose diet (HFrD). The colonization of B. bifidum mediated through the “FcRn-Sialylated IgG-SiaBb2” axis not only highlights the role of SIgG in facilitating bacterial colonization but also offers a novel and promising strategy for combating neuroinflammatory disorders.