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Structural elucidation, gut fermentation, and immunomodulatory mechanisms of β-glucan polymorphs.
Int J Biol Macromol. 2025 Sep; 322(Pt 4):146940.IJ

Abstract

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China.

College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China.

College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China.

College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China.

College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China.

College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China.

College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China.

College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China. Electronic address: zhangmeili22@sina.com.

MeSH

beta-GlucansFermentationAnimalsGastrointestinal MicrobiomeMiceMolecular WeightImmunologic FactorsHumansCell Proliferation

Pub Type(s)

Journal Article

Language

eng

PubMed ID

40846019

Citation

Huo, Rui, et al. "Structural Elucidation, Gut Fermentation, and Immunomodulatory Mechanisms of Β-glucan Polymorphs." International Journal of Biological Macromolecules, vol. 322, no. Pt 4, 2025, p. 146940.

Huo R, Ma S, Miao Y, et al. Structural elucidation, gut fermentation, and immunomodulatory mechanisms of β-glucan polymorphs. Int J Biol Macromol. 2025;322(Pt 4):146940.

Huo, R., Ma, S., Miao, Y., Sun, M., Wang, R., Li, D., Jia, T., & Zhang, M. (2025). Structural elucidation, gut fermentation, and immunomodulatory mechanisms of β-glucan polymorphs. International Journal of Biological Macromolecules, 322(Pt 4), 146940. https://doi.org/10.1016/j.ijbiomac.2025.146940

Huo R, et al. Structural Elucidation, Gut Fermentation, and Immunomodulatory Mechanisms of Β-glucan Polymorphs. Int J Biol Macromol. 2025;322(Pt 4):146940. PubMed PMID: 40846019.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Structural elucidation, gut fermentation, and immunomodulatory mechanisms of β-glucan polymorphs. AU - Huo,Rui, AU - Ma,Sarina, AU - Miao,Ying, AU - Sun,Minjun, AU - Wang,Rui, AU - Li,Dongyan, AU - Jia,Tong, AU - Zhang,Meili, Y1 - 2025/08/20/ PY - 2025/6/2/received PY - 2025/8/11/revised PY - 2025/8/15/accepted PY - 2025/9/7/medline PY - 2025/8/23/pubmed PY - 2025/8/22/entrez KW - Beta glucan KW - Intestinal flora KW - Macrophages SP - 146940 EP - 146940 JF - International journal of biological macromolecules JO - Int J Biol Macromol VL - 322 IS - Pt 4 N2 - 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. SN - 1879-0003 UR - https://www.unboundmedicine.com/medline/citation/40846019/Structural_elucidation DB - PRIME DP - Unbound Medicine ER -