Konjac Glucomannan Oligosaccharides Prevent Intestinal Inflammation Through SIGNR1-Mediated Regulation of Alternatively Activated Macrophages

Authors

Jiqing Tang, Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
Jun Liu, Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
Qiaojuan Yan, Key Laboratory of Food Bioengineering (China National Light Industry), College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
Zhenglong Gu, Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
Avery August, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 13843, USA.
Weishan Huang, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, 13843, USA.
Zhengqiang Jiang, Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.

Document Type

Article

Publication Date

10-1-2021

Abstract

SCOPE: Konjac glucomannan oligosaccharides (KMOS) are prebiotics and may improve intestinal immunity through modulation of macrophage function. However, the underlying molecular mechanisms were unclear. METHODS AND RESULTS: Using a mouse model of dextran sulfated sodium (DSS)-induced acute colitis, the study demonstrates here that KMOS (400 mg kg d ) can ameliorate intestinal inflammation in a macrophage dependent manner. Oral exposure to KMOS prevents DSS-induced intestinal pathology, improves epithelial integrity, and decreases accumulation of colonic inflammatory leukocytes and cytokines. The therapeutic effects of KMOS are dependent on the function of macrophages, as depletion of macrophages abolished the effects. In colonic lamina propria of DSS-treated mice, as well as in vitro culture of bone marrow derived macrophages (BMDMs), KMOS skews reprogramming of classically activated macrophages (CAM/M1) into alternatively activated macrophages (AAM/M2). The study further determines that the activation of SIGNR1/phospho-c-Raf (S338)/phospho-p65 (S276)/acetyl-p65 (K310) pathway is responsible for KMOS-induced AAM/M2 polarization. Blockage of SIGNR1 abolishes KMOS-induced AAM/M2 polarization of activated macrophages, expression of phospho-p65 (S276) in colonic macrophages, and alleviation of DSS-induced colitis in mice, suggesting that SIGNR1 is critical for macrophage responses to KMOS. CONCLUSIONS: This study reveals a SIGNR1-mediated macrophage-dependent pathway that supports regulatory function of KMOS in host immunity and intestinal homeostasis.

Publication Source (Journal or Book title)

Molecular nutrition & food research

First Page

e2001010

Recommended Citation

Tang, J., Liu, J., Yan, Q., Gu, Z., August, A., Huang, W., & Jiang, Z. (2021). Konjac Glucomannan Oligosaccharides Prevent Intestinal Inflammation Through SIGNR1-Mediated Regulation of Alternatively Activated Macrophages. Molecular nutrition & food research, 65 (20), e2001010. https://doi.org/10.1002/mnfr.202001010