目的 探究灵芝多糖通过调控肠道微生态减轻辐射所致小鼠小肠损伤的作用。方法 将C57BL/6J雄性小鼠随机分为空白对照组、辐射模型组和灵芝多糖组,每组15只,分别灌胃生理盐水和150 mg/（kg·bw）灵芝多糖,每日一次,连续28 d;第15 d时,给予辐射模型组和灵芝多糖组小鼠6 Gy一次性全身照射;第27 d时,收集各组小鼠新鲜粪便;第28 d时,麻醉后处死小鼠取其血清、小肠组织,采用HE染色、ELISA法、Western blot等分析小肠辐射损伤相关指标;通过16S rRNA高通量测序和气相色谱-质谱联用（GC-MS）分析小鼠肠道菌群多样性与结构、短链脂肪酸（short-chain fatty acids, SCFAs）含量;采用Pearson相关性分析,探讨菌群-代谢物-宿主指标间的关联。结果 与辐射模型组相比,灵芝多糖干预显著减轻了辐射引起的肠黏膜病理损伤,降低了血清D-乳酸（D-lactic acid, D-LA）含量、二胺氧化酶（diamine oxidase, DAO）活力、内毒素（lipopolysaccharide, LPS）含量（P<0.05）,上调了小肠组织闭锁小带蛋白1（zona occludens 1, ZO-1）、紧密连接蛋白1（claudin1）和粘蛋白2（mucin 2, MUC2）的表达（P<0.05）;同时,灵芝多糖干预缓解了小肠组织氧化应激与炎性因子水平,降低丙二醛（malondialdehyde, MDA）含量,升高超氧化物歧化酶（superoxide dismutase, SOD）、过氧化氢酶（catalase, CAT）活力,降低促炎因子白细胞介素-1β（interleukin 1β, IL-1β）、肿瘤坏死因子-α（tumor necrosis factor α, TNF-α）水平,升高抗炎因子白细胞介素-10 （interleukin 10, IL-10）水平（P<0.05）;灵芝多糖干预使辐射后的菌群多样性显著升高（P<0.05）,并显著提高了粪便中乙酸和丁酸的含量（P<0.05）;相关性分析表明,Alistipes、Odoribacter、Enterorhabdus等菌属与宿主氧化应激、炎性因子水平及肠屏障指标改善相关,而另一部分菌属Eubacterium_xylanophilum_group、Mucispirillum、Faecalibaculum、Turicibacter、Eubacterium_siraeum_group等与SCFAs水平变化相关。结论 灵芝多糖通过改善肠道微生态,减轻小肠辐射损伤。
Abstract
Objective To investigate the effects of Ganoderma lucidum polysaccharides on intestinal microecology to reduce radiation-induced small intestine damage in mice. Methods C57BL/6J male mice were randomly divided into three groups: blank control group, radiation model group and Ganoderma lucidum polysaccharides group, with 15 mice in each group. Mice were given orally with saline or 150 mg/(kg·bw) Ganoderma lucidum polysaccharides once a day for 28 days. On the 15th day, mice in the radiation model group and the Ganoderma lucidum polysaccharides group were given a single whole-body 6 Gy dose of irradiation. On the 27th day, fresh feces samples were collected. On the 28th day, the samples of sera and small intestine tissue were taken after anesthesia. The radiation damage of small intestine was assessed by HE staining, ELISA method, and Western blot analysis. 16S rRNA high-throughput sequencing and gas chromatography-mass spectrometry (GC-MS) were used to analyze the changes of intestinal microbiota and short-chain fatty acids (SCFAs). Pearson correlation analysis was used to explore the associations among microbiota, metabolites and intestinal parameters. Results Compared with the radiation model group, Ganoderma lucidum polysaccharides intervention significantly improved pathological changes of intestinal mucosa caused by radiation, reduced serum D-lactate (D-LA) content, diamine oxidase (DAO) activity, and lipopolysaccharide (LPS) content (P<0.05), and up-regulated the expression of zona occludens 1(ZO-1), claudin1 and mucin 2 (MUC2) (P<0.05）. Meanwhile, Ganoderma lucidum polysaccharides also relieved oxidative stress and inflammation by reducing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) and catalase (CAT) activities, decreasing the levels of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and increasing anti-inflammatory cytokine interleukin-10 (IL-10) level (P<0.05). Ganoderma lucidum polysaccharides significantly improved radiation-induced dysbacteriosis and increased the contents of acetic acid and butyric acid in feces (P<0.05). Correlation analysis showed that Alistipes, Odoribacter, Enterorhabdus and other bacteria were correlated with the improvements in oxidative stress, inflammation and intestinal barrier function, while other genera Eubacterium_ xylanophilum_ group, Mucispirillum, Faecalibaculum, Turicibacter, Eubacterium_siraeum_group, etc. were related to the levels of short-chain fatty acids. Conclusion Ganoderma lucidum polysaccharides reduce radiation-induced small intestine damage possibly by improving the intestinal microecology.
关键词
灵芝多糖 /
辐射损伤 /
肠道菌群 /
肠道屏障 /
短链脂肪酸
Key words
Ganoderma lucidum polysaccharides /
radiation-induced injury /
gut microbiota /
intestinal barrier /
short-chain fatty acids
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Tang LF, Tang FL, Zhou H, et al. Bacillus Coagulans BC99 protects ionizing radiation-induced intestinal injury and modulates gut microbiota and metabolites in mice[J]. Mol Nutr Food Res, 2025, 69: e70057.
[2] Xin JY, Wang J, Ding QQ, et al. Potential role of gut microbiota and its metabolites in radiation-induced intestinal damage[J]. Ecotoxicol Environ Saf, 2022, 248: 114341.
[3] Fernandes A, Oliveira A, Soares R, et al. The effects of ionizing radiation on gut microbiota, a systematic review[J]. Nutrients, 2021, 13: 3025.
[4] Shi N, Li N, Duan X, et al. Interaction between the gut microbiome and mucosal immune system[J]. Military Med Res, 2017, 4: 14.
[5] Li Y, Zhang Y, Wei K, et al. Review: effect of gut microbiota and its metabolite SCFAs on radiation-induced intestinal injury[J]. Front Cell Infect Microbiol, 2021, 11: 577236.
[6] Cui M, Xiao H, Li Y, et al. Faecal microbiota transplantation protects against radiation-induced toxicity[J]. EMBO Mol Med, 2017, 9: 448–461.
[7] Yue T, Dong Y, Huo Q, et al. Nicotinamide riboside alleviates ionizing radiation-induced intestinal senescence by alleviating oxidative damage and regulating intestinal metabolism[J]. J Adv Res, 2025, 72: 421–432
[8] Ji L, Cui P, Zhou S, et al. Advances of amifostine in radiation protection: administration and delivery[J]. Mol Pharm, 2023, 20: 5383–5395.
[9] Li W, Zhou Q, Lv B, et al. Ganoderma lucidum polysaccharide supplementation significantly activates T-cell-mediated antitumor immunity and enhances anti-PD-1 immunotherapy efficacy in colorectal cancer[J]. J Agric Food Chem, 2024, 72: 12072–12082.
[10] Zhang N, Han Z, Zhang R, et al. Ganoderma lucidum polysaccharides ameliorate acetaminophen-induced acute liver injury by inhibiting oxidative stress and apoptosis along the Nrf2 pathway[J]. Nutrients, 2024, 16: 1859.
[11] Zhao W, Jiang X, Deng W, et al. Antioxidant activities of Ganoderma lucidum polysaccharides and their role on DNA damage in mice induced by cobalt-60 gamma-irradiation[J]. Food Chem Toxicol, 2012, 50: 303–309.
[12] Seweryn E, Ziała A, Gamian A.Health-promoting of polysaccharides extracted from Ganoderma lucidum[J]. Nutrients, 2021, 13: 2725.
[13] 于纯淼,董婉茹,连莲, 等. 灵芝多糖抗电离辐射作用实验研究[J]. 辽宁中医药大学学报, 2019, 21: 40-43.
[14] González A, Atienza V, Montoro A, et al. Use of Ganoderma lucidum (Ganodermataceae, Basidiomycota) as radio-protector[J]. Nutrients, 2020, 12: 1143.
[15] Álvarez-Mercado AI, Plaza-Diaz J.Dietary polysaccharides and gut microbiota ecosystem[J]. Nutrients, 2022, 14: 4285.
[16] Yu C, Fu J, Guo L, et al. UPLC-MS-based serum metabolomics reveals protective effect of Ganoderma lucidum polysaccharide on ionizing radiation injury[J]. J Ethnopharmacol, 2020, 258: 112814.
[17] Li W, Wang X, Dong Y, et al. Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice[J]. Aging Cell, 2023, 22: e13976.
[18] Zhang Y, Wang L, Xu M, et al. Smart oral administration of polydopamine-coated nanodrugs for efficient attenuation of radiation-induced gastrointestinal syndrome[J]. Adv Healthc Mat, 2020, 9: 1901778.
[19] Sylvestre M, Di Carlo S E, Peduto L. Stromal regulation of the intestinal barrier[J]. Mucosal Immunol, 2023, 16: 221–231.
[20] Chen Y, Cui W, Li X, et al. Interaction between commensal bacteria, immune response and the intestinal barrier in inflammatory bowel disease[J]. Front Immunol, 2021, 12: 761981.
[21] Usuda H, Okamoto T, Wada K.Leaky gut: effect of dietary fiber and fats on microbiome and intestinal barrier[J]. Int J Mol Sci, 2021, 22: 7613.
[22] Acharya M, Venkidesh BS, Mumbrekar KD.Bacterial supplementation in mitigation of radiation-induced gastrointestinal damage[J]. Life Sci, 2024, 353: 122921.
[23] Iyer N, Corr SC.Gut microbial metabolite-mediated regulation of the intestinal barrier in the pathogenesis of inflammatory bowel disease[J]. Nutrients, 2021, 13: 4259.
[24] Liu XR, Zhu N, Hao YT, et al. Radioprotective effect of whey hydrolysate peptides against γ-radiation-induced oxidative stress in BALB/c mice[J]. Nutrients, 2021, 13: 816.
[25] Di Vincenzo F, Del Gaudio A, Petito V, et al. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review[J]. Intern Emerg Med, 2024, 19: 275-293.
[26] He Y, Li,D Ye H, et al. Oxidative stress-induced CDO1 glutathionylation regulates cysteine metabolism and sustains redox homeostasis under ionizing radiation[J]. Redox Biol, 2025, 83: 103656.
[27] Mohammadgholi M, Hosseinimehr SJ.Crosstalk between oxidative stress and inflammation induced by ionizing radiation in healthy and cancerous cells[J]. Currt Med Chem, 2024, 31: 2751–2769.
[28] Moreira Gobis ML, Goulart de Souza-Silva T, de Almeida Paula HA. The impact of a western diet on gut microbiota and circadian rhythm: a comprehensive systematic review of in vivo preclinical evidence[J]. Life Sci, 2024, 349: 122741.
[29] Chen YJ, Wu H, Wu SD, et al. Parasutterella, in association with irritable bowel syndrome and intestinal chronic inflammation[J]. J Gastroenterol Hepatol, 2018, 33: 1844–1852.
[30] Chen L, Ye Z, Li J, et al. Gut bacteria Prevotellaceae related lithocholic acid metabolism promotes colonic inflammation[J]. J Transl Med, 2025, 23: 55.
[31] Elinav E, Strowig T, Kau AL, et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis[J]. Cell, 2011, 145: 745–757.
[32] Zhang Y, Zhang B, Dong L, et al. Potential of omega-3 polyunsaturated fatty acids in managing chemotherapy-or radiotherapy-related intestinal microbial dysbiosis[J]. Advs Nutr (Bethesda, Md.), 2019, 10: 133–147.
[33] Cao YG, Bae S, Villarreal J,,et al. Faecalibaculum rodentium remodels retinoic acid signaling to govern eosinophil-dependent intestinal epithelial homeostasis[J]. Cell Host Microbe. Faecalibaculum rodentium remodels retinoic acid signaling to govern eosinophil-dependent intestinal epithelial homeostasis[J]. Cell Host Microbe, 2022, 30: 1295–1310.e8.
[34] Parker BJ, Wearsch PA, Veloo ACM, et al. The genus alistipes: gut bacteria with emerging implications to inflammation, cancer, and mental health[J]. Front Immunol, 2020, 11: 906.
[35] Liu X, Zhang Y, Li W, et al. Fucoidan ameliorated dextran sulfate sodium-induced ulcerative colitis by modulating gut microbiota and bile acid metabolism[J]. J Agric Food Chem, 2022, 70: 14864–14876.
[36] Lin TC, Soorneedi A, Guan Y, et al. Turicibacter fermentation enhances the inhibitory effects of Antrodia camphorata supplementation on tumorigenic serotonin and Wnt pathways and promotes ROS-mediated apoptosis of Caco-2 cells[J]. Front Pharmacol, 2023, 14: 1203087.
[37] Zheng Y, Pang X, Zhu X, et al. Lycium barbarum mitigates radiation injury via regulation of the immune function, gut microbiota, and related metabolites[J]. Biomed Pharmacother, 2021, 139: 111654.
[38] Xie LW, Lu HY, Tang LF, et al. Probiotic consortia protect the intestine against radiation injury by improving intestinal epithelial homeostasis[J]. Int J Radiat Oncol Biol, Phys, 2024, 120: 189–204.
[39] Zhang H, Dong M, Zheng J, et al. Fecal bacteria-free filtrate transplantation is proved as an effective way for the recovery of radiation-induced individuals in mice[J]. Front Cell Infect Microbiol, 2024, 13: 1343752.
[40] Lu H, Xie L, Guo L, et al. EGCG protects intestines of mice and pelvic cancer patients against radiation injury via the gut microbiota/D-tagatose/AMPK axis[J]. Radiother Oncol, 2025, 202: 110608.
[41] 刘颖茵, 陈纳川, 何华星, 等. 丁酸钠可能通过ERK和STAT 3磷酸化及抑制铁死亡发挥其防治炎症性肠病作用[J]. 营养学报, 2025, 47: 367-373.
[42] 张乃珣, 尹红力, 刘冉, 等. 茶黄素与真菌多糖联合清除ABTS自由基活性的比较[J]. 现代食品科技, 2017, 33: 21-28, 34.
[43] 刘丹, 吴志龙, 蒋帆, 等. 灵芝菌丝体速溶粉的体外抗氧化作用[J]. 中国食用菌, 2016, 35: 63-66.
[44] Ren L, Zhang J, Zhang T.Immunomodulatory activities of polysaccharides from Ganoderma on immune effector cells[J]. Food Chem, 2021, 340: 127933.
[45] Chen Y, Zeng X, Gong X, et al. Ganoderma lucidum polysaccharides target the gut-brain axis: unveiling a novel mechanism for ameliorating aging-induced cognitive impairment and oxidative stress[J]. Int J Biol Macromol, 2025, 337: 149519.
基金
国家自然科学基金（No. 81903307）
PDF(11283 KB)
