长双歧杆菌CCFM1206分离自健康成人粪便,可将萝卜硫苷转化成萝卜硫素(sulforaphane, SFN),该文研究了西兰花种子水提物(broccoli seed extract, BSE)以及其联合不同剂量的长双歧杆菌CCFM1206(108、109和1010CFU)对小鼠肠内SFN水平的调控以及对右旋糖酐硫酸酯钠(dextran sulfate sodium, DSS)诱导结肠炎的缓解作用。研究发现,与BSE组相比,补充109和1010 CFU长双歧杆菌CCFM1206后,小鼠粪便中SFN和N-乙酰萝卜硫素(sulforaphane N-acetyl-L-cysteine,SFN-NAC)总量由30.84 μmol/g分别提高至45.48和49.32 μmol/g(P<0.05);仅摄入BSE(200 mg/kg小鼠体重),能有效缓解小鼠结肠缩短、降低炎症因子水平(IL-6、IL-1β和TNF-α)、增强抗氧化酶活力(GSH、SOD)、上调紧密连接蛋白的基因转录水平和蛋白表达水平,激活Nrf2信号通路并抑制NF-κB信号通路;补充108 CFU长双歧杆菌CCFM1206效果与BSE无显著差异,而补充109和1010 CFU长双歧杆菌CCFM1206在激活Nrf2和抑制NF-κB信号通路方面更加优异,这可能与产生更多SFN有关。该研究可为开发缓解结肠炎的膳食制剂提供理论依据和剂量参考。
Bifidobacterium longum CCFM1206 was isolated from the feces of healthy adults and can transform sulforaphane into sulforaphane (SFN).This paper studied the regulation of water extract of broccoli seeds (BSE) and different doses of B.longum CCFM1206 (108, 109 and 1010 CFU) on the levels of SFN in the intestine of mice and the alleviation of dextran sulfate sodium (DSS) induced colitis.Compared with the BSE group, supplementation with 109 and 1010 CFU of B.longum CCFM1206 significantly increased the total amount of SFN and N-acetyl sulforaphane (SFN-NAC) in the feces of mice from 30.84 μmol/g to 45.48 and 49.32 μmol/g (P<0.05), respectively.Dietary BSE (200 mg/kg body weight) can effectively alleviate colon shortening, reduce the levels of inflammatory factors (IL-6, IL-1β and TNF-α), enhance the antioxidant enzyme activities (GSH, SOD), up-regulate the gene transcription and protein expression of tight junction proteins, activate Nrf2 signaling pathway and inhibit NF- κB signal pathway.Supplementation with 108 CFU of B.longum CCFM1206 showed no significant differences from BSE, while supplementation with 109 and 1010 CFU of B.longum CCFM1206 more significantly activated Nrf2 and inhibited NF-κB signal pathway, which may be related to the generation of more SFNs.This study provides theoretical basis and dose reference for the development of dietary preparations to alleviate colitis.
[1] SUBEDI L, LEE J H, YUMNAM S, et al.Anti-inflammatory effect of sulforaphane on LPS-activated microglia potentially through JNK/AP-1/NF-κB inhibition and Nrf2/HO-1 activation[J].Cells, 2019, 8(2):194.
[2] QIN W S, DENG Y H, CUI F C.Sulforaphane protects against acrolein-induced oxidative stress and inflammatory responses:Modulation of Nrf-2 and COX-2 expression[J].Archives of Medical Science:AMS, 2016, 12(4):871-880.
[3] YE J H, HUANG L Y, TEREFE N S, et al.Fermentation-based biotransformation of glucosinolates, phenolics and sugars in retorted broccoli puree by lactic acid bacteria[J].Food Chemistry, 2019, 286:616-623.
[4] COCETTA V, CATANZARO D, BORGONETTI V, et al.A fixed combination of probiotics and herbal extracts attenuates intestinal barrier dysfunction from inflammatory stress in an in vitro model using Caco-2 cells[J].Recent Patents on Food, Nutrition and Agriculture, 2019, 10(1):62-69.
[5] HUBBARD T D, MURRAY I A, NICHOLS R G, et al.Dietary broccoli impacts microbial community structure and attenuates chemically induced colitis in mice in an Ah receptor dependent manner[J].Journal of Functional Foods, 2017, 37:685-698.
[6] ZHANG T, HOLMAN J, MCKINSTRY D, et al.A steamed broccoli sprout diet preparation that reduces colitis via the gut microbiota[J].The Journal of Nutritional Biochemistry, 2023, 112:109215.
[7] WU J Y, GUO W L, CUI S M, et al.Broccoli seed extract rich in polysaccharides and glucoraphanin ameliorates DSS-induced colitis via intestinal barrier protection and gut microbiota modulation in mice[J].Journal of the Science of Food and Agriculture, 2023, 103(4):1749-1760.
[8] WU J Y, CUI S M, TANG X, et al.Bifidobacterium longum CCFM1206 promotes the biotransformation of glucoraphanin to sulforaphane that contributes to amelioration of dextran-sulfate-sodium-induced colitis in mice[J].Journal of Agricultural and Food Chemistry, 2023, 71(2):1100-1112.
[9] REJCHRT S, KVETINA J, KUNES M, et al.Tu1632 The probiotic Lactobacillus casei Dn 114001 significantly influenced absorption and metabolism of 5-aminosalicylic acid in experimental porcine inflammatory bowel disease induced by dextran sulfate sodium[J].Gastroenterology, 2013, 144(5):S810.
[10] LIU Y W, ONG W K, SU Y W, et al.Anti-inflammatory effects of Lactobacillus brevis K65 on RAW 264.7 cells and in mice with dextran sulphate sodium-induced ulcerative colitis[J].Beneficial Microbes, 2016, 7(3):387-396.
[11] LEE I A, BAE E A, LEE J H, et al.Bifidobacterium longum HY8004 attenuates TNBS-induced colitis by inhibiting lipid peroxidation in mice[J].Inflammation Research, 2010, 59(5):359-368.
[12] CHEN Y, JIN Y, STANTON C, et al.Dose-response efficacy and mechanisms of orally administered CLA-producing Bifidobacterium breve CCFM683 on DSS-induced colitis in mice[J].Journal of Functional Foods, 2020, 75:104245.
[13] MA C M, YANG D X, WANG B W, et al.Gasdermin D in macrophages restrains colitis by controlling cGAS-mediated inflammation[J].Science Advances, 2020, 6(21):eaaz6717.
[14] NAKAMURA A, KURIHARA S, TAKAHASHI D, et al.Symbiotic polyamine metabolism regulates epithelial proliferation and macrophage differentiation in the colon[J].Nature Communications, 2021, 12(1):2105.
[15] GUO W L, MAO B Y, CUI S M, et al.Protective effects of a novel probiotic Bifidobacterium pseudolongum on the intestinal barrier of colitis mice via modulating the Pparγ/STAT3 pathway and intestinal microbiota[J].Foods, 2022, 11(11):1551.
[16] WU J Y, CUI S M, LIU J S, et al.The recent advances of glucosinolates and their metabolites:Metabolism, physiological functions and potential application strategies[J].Critical Reviews in Food Science and Nutrition, 2023, 63(20):4217-4234.
[17] CRAMER J M, TERAN-GARCIA M, JEFFERY E H.Enhancing sulforaphane absorption and excretion in healthy men through the combined consumption of fresh broccoli sprouts and a glucoraphanin-rich powder[J].The British Journal of Nutrition, 2012, 107(9):1333-1338.
[18] NEURATH M F.Cytokines in inflammatory bowel disease[J].Nature Reviews Immunology, 2014, 14(5):329-342.
[19] BHATTACHARYYA A, CHATTOPADHYAY R, MITRA S,et al.Oxidative stress:An essential factor in the pathogenesis of gastrointestinal mucosal diseases[J].Physiological Reviews, 2014, 94(2):329-354.
[20] HWANG J, JIN J, JEON S, et al.SOD1 suppresses pro-inflammatory immune responses by protecting against oxidative stress in colitis[J].Redox Biology, 2020, 37:101760.
[21] CUI L, GUAN X N, DING W B, et al.Scutellaria baicalensis Georgi polysaccharide ameliorates DSS induced ulcerative colitis by improving intestinal barrier function and modulating gut microbiota[J].International Journal of Biological Macromolecules, 2021, 166:1035-1045.
[22] LEE J S, SURH Y J.Nrf2 as a novel molecular target for chemoprevention[J].Cancer Letters, 2005, 224(2):171-184.
[23] WU S, ZHOU Y, YANG G X, et al.Sulforaphane-cysteine induces apoptosis by sustained activation of ERK1/2 and caspase 3 in human glioblastoma U373MG and U87MG cells[J].Oncology Reports, 2017, 37(5):2829-2838.
[24] KOBAYASHI E H, SUZUKI T, FUNAYAMA R, et al.Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription[J].Nature Communications, 2016, 7(1):11624.
