该研究采用3%(质量分数)右旋葡萄糖酸钠(dextran sodium sulfate, DSS)诱导建立溃疡性结肠炎(ulcerative colitis, UC)小鼠模型,探究岩藻多糖对UC的治疗作用及对肠道菌群的影响。将40只雄性C57BL/6小鼠随机分为对照组、模型组、美沙拉嗪组和岩藻多糖组,通过自由饮用3%(质量分数)DSS建立UC小鼠模型。自造模第1天起,美沙拉嗪组和岩藻多糖组灌胃给予剂量为10 mg/kg的相应药物,对照组和模型组给予相同体积的生理盐水,连续给药9 d。每日监测小鼠的一般情况如体质量变化、粪便状态;观察小鼠结肠组织病变情况;测定小鼠结肠组织中炎症因子分泌情况;对小鼠粪便样品进行16S rRNA高通量测序。与模型组相比,岩藻多糖能够有效缓解UC小鼠症状,减轻结肠组织病理损伤 (P<0.001);抑制炎症因子白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α的分泌;经岩藻多糖治疗后,UC小鼠肠道菌群的多样性及丰度提高,在门水平上,厚壁菌门/拟杆菌门的值降低;在属水平上,致病菌幽门螺杆菌的相对丰度降低,有益菌Muribaculaceae_unclassified、Alistipes和Alloprevotella相对丰度增加。岩藻多糖可有效缓解UC小鼠病症,其可能通过恢复肠道菌群多样性及丰度,调节肠道菌群的组成,发挥对UC的治疗作用。
This study aimed to investigate the therapeutic effect of fucoidan on dextran sodium sulfate (DSS) induced ulcerative colitis (UC) mice and to explore its influence on the intestinal flora of UC mice.Forty male C57BL/6 mice were randomly divided into control group, model group, mesalazine group and fucoidan group.Mice were provided with distilled drinking water containing 3.0% DSS for 7 days to induce acute colitis.The mice in the mesalazine and fucoidan groups were given with the corresponding drug at a dose of 10 mg/kg for 9 days. The body weight and fecal status were recorded daily, the secretion of inflammatory factors were measured in the colonic tissues of mice by ELISA,the histopathological changes of the colon were observed by HE, and the fecal samples of mice were performed by 16S rRNA high-throughput sequencing.Compared with the model group, fucoidan could effectively alleviate the symptoms of UC mice, slow down the weight loss (P<0.05), improve diarrhea (P<0.05) and blood in stool (P<0.01),reduce the histopathological damage of colon, decrease the histopathological score of colon (P<0.001),inhibit the secretion of inflammatory factors IL-1β (P<0.01), IL-6 (P<0.001) and TNF-α (P<0.001).16S rDNA sequencing results showed that the diversity and abundance of intestinal flora in UC mice treated with fucoidan increased.At the phylum level, the values of the Firmicutes/Bacteroides decreased.At the genus level, the relative abundance of the pathogenic bacterium Helicobacter pylori decreased and the relative abundance of the beneficial bacteria Muribaculaceae_unclassified, Alistipes, and Alloprevotella increased.Fucoidan can effectively alleviate the disease in UC mice, and it may play a therapeutic role in UC by restoring the diversity and abundance of intestinal flora and regulating the composition of intestinal flora.
[1] 杨小冰, 金明玉, 吴小禾, 等.膳食营养素与炎症性肠病关系研究进展[J].食品科学, 2019, 40(9):309-315.
YANG X B, JIN M Y, WU X H, et al.Progress in understanding the relationship between dietary nutrients and inflammatory bowel disease[J].Food Science, 2019, 40(9):309-315.
[2] NG S C, SHI H Y, HAMIDI N, et al.Worldwide incidence and prevalence of inflammatory bowel disease in the 21 st century:A systematic review of population-based studies[J].Lancet, 2017, 390(10114):2769-2778.
[3] KAWALEC P.Indirect costs of inflammatory bowel diseases:Crohn′s disease and ulcerative colitis.A systematic review[J].Archives of Medical Science:AMS, 2016, 12(2):295-302.
[4] ZHANG L, WANG X Z, ZHANG X.Modulation of intestinal flora by dietary polysaccharides:A novel approach for the treatment and prevention of metabolic disorders[J].Foods, 2022, 11(19):2961.
[5] FARRELL R J, PEPPERCORN M A.Ulcerative colitis[J].The Lancet, 2002, 359(9303):331-340.
[6] ZHOU H Y, GUO B, LUFUMPA E, et al.Comparative of the effectiveness and safety of biological agents, tofacitinib, and fecal microbiota transplantation in ulcerative colitis:Systematic review and network meta-analysis[J].Immunological Investigations, 2021, 50(4):323-337.
[7] CONG J, WANG P, GAI H R, et al.Effects of compound prebiotics as prophylactic and therapeutic supplementation in a mouse model of acute colitis[J].Applied Microbiology and Biotechnology, 2023, 107(7-8):2597-2609.
[8] WANG Y, XING M C, CAO Q, et al.Biological activities of fucoidan and the factors mediating its therapeutic effects:A review of recent studies[J].Marine Drugs, 2019, 17(3):183.
[9] 王祺瑶, 卢畅, 彭婵妮, 等.海藻岩藻多糖抗肿瘤活性研究新进展[J].食品安全质量检测学报, 2022, 13(7):2043-2050.
WANG Q Y, LU C, PENG C N, et al.Recent progress on the antitumor activity of fucoidan[J].Journal of Food Safety and Quality, 2022, 13(7):2043-2050.
[10] HUSNI A, IZMI N, AYUNANI F Z, et al.Characteristics and antioxidant activity of fucoidan from Sargassum hystrix:Effect of extraction method[J].International Journal of Food Science, 2022, 2022:3689724.
[11] KIM H I, KIM D S, JUNG Y, et al.Immune-enhancing effect of sargassum horneri on cyclophosphamide-induced immunosuppression in BALB/c mice and primary cultured splenocytes[J].Molecules, 2022, 27(23):8253.
[12] LIU X X, ZHANG Y H, LI W H, et al.Fucoidan ameliorated dextran sulfate sodium-induced ulcerative colitis by modulating gut microbiota and bile acid metabolism[J].Journal of Agricultural and Food Chemistry, 2022, 70(47):14864-14876.
[13] VESPA E, D′AMICO F, SOLLAI M, et al.Histological scores in patients with inflammatory bowel diseases:The state of the art[J].Journal of Clinical Medicine, 2022, 11(4):939.
[14] O′SHEA C J, O′DOHERTY J V, CALLANAN J J, et al.The effect of algal polysaccharides laminarin and fucoidan on colonic pathology, cytokine gene expression and Enterobacteriaceae in a dextran sodium sulfate-challenged porcine model[J].Journal of Nutritional Science, 2016, 5:e15-e15.
[15] 黄金莉, 黄娟, 李瑶, 等.岩藻多糖对代谢性疾病及肠道菌群调节作用研究进展[J].现代预防医学, 2021, 48(16):3017-3023;3028.
HUANG J L, HUANG J, LI Y, et al.Advances in research of fucoidan on metabolic diseases and gut microbiota[J].Modern Preventive Medicine, 2021, 48(16):3 017-3023;3028.
[16] EOM T, KIM Y S, CHOI C H, et al.Current understanding of microbiota- and dietary-therapies for treating inflammatory bowel disease[J].Journal of Microbiology, 2018, 56(3):189-198.
[17] SCHROEDER B O, BIRCHENOUGH G M H, STÅHLMAN M, et al.Bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration[J].Cell Host & Microbe, 2018, 23(1):27-40e7.
[18] PEREIRA F C, WASMUND K, COBANKOVIC I, et al.Rational design of a microbial consortium of mucosal sugar utilizers reduces clostridiodes difficile colonization[J].Nature Communications, 2020, 11(1):5104.
[19] ROBERT H, PAYROS D, PINTON P, et al.Impact of mycotoxins on the intestine:Are mucus and microbiota new targets?[J].Journal of Toxicology and Environmental Health.Part B,Critical Reviews, 2017, 20(5):249-275.
[20] PARKER B J, WEARSCH P A, VELOO A C M, et al.The genusalistipes:Gut bacteria with emerging implications to inflammation, cancer, and mental health[J].Frontiers in Immunology, 2020, 11:906.
[21] MEI F F, DUAN Z W, CHEN M X, et al.Effect of a high-collagen peptide diet on the gut microbiota and short-chain fatty acid metabolism[J].Journal of Functional Foods, 2020, 75:104278.
[22] XU Y Q, ZHU Y, LI X T, et al.Dynamic balancing of intestinal short-chain fatty acids:The crucial role of bacterial metabolism[J].Trends in Food Science & Technology, 2020, 100:118-130.
[23] PALACIOS-GORBA C, PINA R, TORTAJADA-GIRBÉS M, et al.Caenorhabditis elegans as an in vivo model to assess fucoidan bioactivity preventing Helicobacter pylori infection[J].Food & Function, 2020, 11(5):4525-4534.
[24] LIN Y, QI X S, LIU H J, et al.The anti-cancer effects of fucoidan:A review of both in vivo and in vitro investigations[J].Cancer Cell International, 2020, 20:154.
[25] TOMORI M, NAGAMINE T, IHA M.Are Helicobacter pylori infection and fucoidan consumption associated with fucoidan absorption?[J].Marine Drugs, 2020, 18(5):235.
[26] 蒋彬, 程译文, 凌宗欣.幽门螺杆菌感染对正常胃部菌群多样性和组成的影响[J].中国微生态学杂志, 2020, 32(10):1145-1149.
JIANG B, CHENG Y W, LING Z X.Effects of Helicobacter pylori on the composition of normal gastric microbiota[J].Chinese Journal of Microecology, 2020, 32(10):1145-1149.
[27] GUO Y J, XU C X, GONG R J, et al.Exosomal CaGa from Helicobacter pylori aggravates intestinal epithelium barrier dysfunction in chronic colitis by facilitating Claudin-2 expression[J].Gut Pathogens, 2022, 14(1):13.
