Structural elucidation, gut fermentation, and immunomodulatory mechanisms of β-glucan polymorphs

This study aimed to investigate through in vitro metabolic experiments how β-glucan conformation influences immune induction, and to preliminarily explore the synergistic anti-inflammatory effects of ellagic acid. Our findings indicated molecular weight as a key determinant of β-glucan activity, primarily influencing the growth of energy metabolism-related gut microbiota and associated gene expression. Low-molecular-weight (LMW) β-1,3/1,4-glucan emerged as the optimal carbon source, selectively enriching butyrate-producing bacteria and stimulating proliferative cellular metabolism. These effects contributed to enhanced intestinal barrier function and the rapid activation of biosynthetic positive regulatory signals. In contrast, high-molecular-weight (HMW) β-glucans displayed sustained, low-level immunostimulatory properties. The branching patterns were found to co-regulate biphasic immune modulation: LMW β-1,3/1,6-glucan, with its rapid metabolic characteristics, induced an active metabolic state that triggered inflammatory responses while simultaneously activating partial negative regulatory mechanisms in early stages. In contrast, HMW β-1,3/1,6-glucan suppressed proliferation- and metabolism-related signaling through delayed metabolic activity. Its unique branching structure mediated dectin-1 recognition, thus driving cellular metabolic reprogramming, maintaining immune homeostasis, and regulating protein translocation in the mitochondrial intermembrane space, besides apoptotic signaling. This study provides a theoretical foundation for the translational application of β-glucans in trained immunity.