Ganoderma lucidum polysaccharide modulates gut microbiota and immune cell function to inhibit inflammation and tumorigenesis in colon

被引:348
作者
Guo, Cuiling [1 ]
Guo, Dandan [1 ]
Fang, Liu [1 ]
Sang, Tingting [1 ]
Wu, Jianjun [1 ]
Guo, Chengjie [1 ]
Wang, Yujie [1 ]
Wang, Ying [1 ]
Chen, Chaojie [1 ]
Chen, Jiajun [1 ]
Chen, Rong [1 ]
Wang, Xingya [1 ]
机构
[1] Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, 260 Baichuan Rd, Hangzhou 311400, Peoples R China
基金
中国国家自然科学基金;
关键词
Ganoderma lucidum polysaccharide; Gut microbiota; Colitis-associated cancer; Inflammation; Macrophage; LPS; COLORECTAL-CANCER; INDUCED COLITIS; DIETARY FIBER; MICE; CARCINOGENESIS; DISEASE; MAPK; DIFFERENTIATION; COLONIZATION; SUPPRESSION;
D O I
10.1016/j.carbpol.2021.118231
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
This study investigated the effects of water-soluble polysaccharide extracted from the sporoderm-removed spores of Ganoderma lucidum (GLP) against AOM/DSS-induced inflammation, tumorigenesis, and gut microbiota modification, which has never been reported before. Our data revealed that GLP (200 and 300 mg/kg) decreased AOM/DSS-induced colitis and tumorigenesis, manifested by significantly reduced disease activity index score, and total number and size of tumors. Furthermore, GLP ameliorated AOM/DSS-induced microbiota dysbiosis, increased short-chain fatty acid production, and alleviated endotoxemia by inhibiting TLR4/MyD88/NF-kappa B signaling. Besides, GLP profoundly improved gut barrier function as evidenced by increased numbers of goblet cells, MUC2 secretion, and tight junction protein expressions. GLP treatment inhibited macrophage infiltration and downregulated IL-1 beta, iNOS, and COX-2 expressions. Additionally, GLP inhibited lipopolysaccharides (LPS)induced inflammation markers and MAPK (JNK and ERK) activation in macrophage RAW264.7, intestinal HT-29, and NCM460 cells. In conclusion, these results indicate that GLP is a promising prebiotic for the treatment of colorectal cancer.
引用
收藏
页数:19
相关论文
共 98 条
[1]   Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function [J].
Abreu, Maria T. .
NATURE REVIEWS IMMUNOLOGY, 2010, 10 (02) :131-143
[2]   Ganoderma lucidum: Persuasive biologically active constituents and their health endorsement [J].
Ahmad, Md Faruque .
BIOMEDICINE & PHARMACOTHERAPY, 2018, 107 :507-519
[3]   Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells [J].
Alrafas, Haider Rasheed ;
Busbee, Philip B. ;
Nagarkatti, Mitzi ;
Nagarkatti, Prakash S. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2019, 106 (02) :467-480
[4]   Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM/DSS mouse model of colon cancer [J].
Bader, Jackie E. ;
Enos, Reilly T. ;
Velazquez, Kandy T. ;
Carson, Meredith S. ;
Nagarkatti, Mitzi ;
Nagarkatti, Prakash S. ;
Chatzistamou, Ioulia ;
Davis, J. Mark ;
Carson, James A. ;
Robinson, Cory M. ;
Murphy, E. Angela .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2018, 314 (01) :G22-G31
[5]   Origin, Differentiation, and Function of Intestinal Macrophages [J].
Bain, Calum C. ;
Schridde, Anika .
FRONTIERS IN IMMUNOLOGY, 2018, 9
[6]   Structure of the gut microbiome following colonization with human feces determines colonic tumor burden [J].
Baxter, Nielson T. ;
Zackular, Joseph P. ;
Chen, Grace Y. ;
Schloss, Patrick D. .
MICROBIOME, 2014, 2
[7]   Colonization of the Human Gut by E. coli and Colorectal Cancer Risk [J].
Bonnet, Mathilde ;
Buc, Emmanuel ;
Sauvanet, Pierre ;
Darcha, Claude ;
Dubois, Damien ;
Pereira, Bruno ;
Dechelotte, Pierre ;
Bonnet, Richard ;
Pezet, Denis ;
Darfeuille-Michaud, Arlette .
CLINICAL CANCER RESEARCH, 2014, 20 (04) :859-867
[8]   The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker [J].
Cammarota, Rosaria ;
Bertolini, Valentina ;
Pennesi, Giuseppina ;
Bucci, Eraldo O. ;
Gottardi, Ornella ;
Garlanda, Cecilia ;
Laghi, Luigi ;
Barberis, Massimo C. ;
Sessa, Fausto ;
Noonan, Douglas M. ;
Albini, Adriana .
JOURNAL OF TRANSLATIONAL MEDICINE, 2010, 8
[9]   Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota [J].
Chang, Chih-Jung ;
Lin, Chuan-Sheng ;
Lu, Chia-Chen ;
Martel, Jan ;
Ko, Yun-Fei ;
Ojcius, David M. ;
Tseng, Shun-Fu ;
Wu, Tsung-Ru ;
Chen, Yi-Yuan Margaret ;
Young, John D. ;
Lai, Hsin-Chih .
NATURE COMMUNICATIONS, 2015, 6
[10]   A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis [J].
Chen, Haitao ;
Zhang, Fan ;
Zhang, Jin ;
Zhang, Xinjie ;
Guo, Yong ;
Yao, Qinghua .
FRONTIERS IN IMMUNOLOGY, 2020, 11