高脂饮食对过敏性鼻炎小鼠致敏影响和肠道菌群改变的研究

doi:10.6040/j.issn.1673-3770.0.2022.137

摘要/Abstract

摘要： 目的探讨高脂饮食(high-fat diet, HFD)对过敏性鼻炎(allergic rhinitis, AR)小鼠致敏程度的影响和肠道菌群的改变及调节机制。方法设置小鼠对照组(CN组),鸡卵白蛋白(ovalbumin, OVA)诱导的过敏性鼻炎小鼠模型组(AR组)和高脂饮食干预的过敏性鼻炎小鼠模型组(HFD-AR组),每组7只。记录每只小鼠打喷嚏和挠鼻的次数,ELISA检测小鼠血清抗OVA的IgE浓度、鼻腔盥洗液的IL-4浓度。对鼻腔黏膜、肺进行组织切片并HE染色。粪便样本总DNA进行抽提,测定纯度及基因组的完整性,用于16S rRNA测序和数据分析。结果 AR组小鼠在OVA刺激后发生挠鼻和打喷嚏的频率高于CN组。与AR组相比,HFD-AR组提高了小鼠挠鼻和打喷嚏的次数。与CN组相比,HFD-AR组和AR组的小鼠血清中抗OVA的特异性IgE水平上升。与CN组比较,HFD-AR组和AR组的小鼠鼻腔盥洗液中IL-4的水平有提高。HFD干预加重了AR组小鼠的鼻黏膜的嗜酸性粒细胞浸润与肺组织的炎细胞浸润。HFD-AR组比AR组的菌群多样性降低,HFD-AR组的菌群数量相较于AR组降低。CN组、AR组和HFD-AR组小鼠之间的肠道菌群结构均出现分离,而组内样本分离度较小。在门水平和属水平上,3组小鼠之间均有大量差异菌群。结论高脂饮食的干预加重了OVA诱导的AR小鼠的症状和组织炎性浸润程度。高脂肪摄入会导致OVA诱导的AR小鼠肠道菌群多样性和丰富度降低。高脂肪饮食加重的小鼠鼻腔炎症状态与肠道菌群失调有关。

关键词: 过敏性鼻炎, 高脂饮食, 肠道菌群, 炎症

Abstract: Objective We investigated the effect of high-fat diet(HFD)on the sensitization of allergic rhinitis(AR)mice and change of intestinal flora and its regulatory mechanism. Methods The control(CN), allergic rhinitis model(AR)induced by chicken ovalbumin(OVA), and allergic rhinitis model(HFD-AR)groups exposed to high-fat diet were set up, with seven mice in each group. The times of sneezing and scratching the nose of each mouse were recorded, and the concentration of anti OVA IgE in serum and IL-4 in nasal lavatory were detected by ELISA. The nasal mucosa and lung were sectioned and stained with HE. Additionally, the total DNA of stool samples was extracted to determine the purity and integrity of the genome for 16S rRNA sequencing and data analysis. Results The frequency of nose scratching and sneezing in the AR group was higher than that in the CN group after OVA stimulation. Compared with the AR group, the HFD-AR group exhibited increased nose scratching and sneezing in mice. Compared with the CN group, the level of specific IgE against OVA in serum and the level of IL-4 in the nasal lavage fluid of mice in the HFD-AR and AR groups increased. HFD intervention aggravated eosinophil infiltration in nasal mucosa and inflammatory cell infiltration in lung tissue of AR group mice. The diversity and number of flora in the HFD-AR group were lower than those in the AR group. The intestinal microflora structure of mice in the CN, AR, and HFD-AR groups were isolated, while the sample isolation in the group was small. At the phyla and genus levels, numerous different bacterial populations were observed among the three groups of mice. Conclusion The intervention of high-fat diet aggravates the symptoms and inflammatory infiltration of tissues in OVA-induced AR mice and reduces the diversity and abundance of intestinal flora. The nasal inflammation of mice aggravated by high-fat diet is related to intestinal flora imbalance.

Key words: Allergic rhinitis, High fat diet, Intestinal flora, Inflammation

中图分类号:

R765

王惟一,时蕾,张志玉,张贵玲,时光刚. 高脂饮食对过敏性鼻炎小鼠致敏影响和肠道菌群改变的研究[J]. 山东大学耳鼻喉眼学报, 2023, 37(3): 21-29.

WANG Weiyi, SHI Lei, ZHANG Zhiyu, ZHANG Guiling, SHI Guanggang. Effects of high fat diet on allergic rhinitis mice and intestinal flora[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(3): 21-29.

参考文献

[1] 中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组, 中华医学会耳鼻咽喉头颈外科学分会鼻科学组. 中国慢性鼻窦炎诊断和治疗指南(2018)[J]. 中华耳鼻咽喉头颈外科杂志, 2019, 54(2): 81-100. doi:10.3760/cma.j.issn.1673-0860.2019.02.001 Subspecialty Group of Rhinology, Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery, Subspecialty Group of Rhinology, et al. Chinese guidelines for diagnosis and treatment of chronic rhinosinusitis(2018)[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2019, 54(2): 81-100. doi:10.3760/cma.j.issn.1673-0860.2019.02.001
[2] Hertzen Leena-von,Hanski Ilkka,Haahtela Tari, et al. Biodiversity loss and inflammatory diseases are two global megatrends that might be related[J]. Natural immunity, 2011(11): 1089-1093. doi:10.1038/embor.2011.195
[3] Neef A, Sanz Y. Future for probiotic science in functional food and dietary supplement development[J]. Curr Opin Clin Nutr Metab Care, 2013, 16(6): 679-687. doi:10.1097/MCO.0b013e328365c258
[4] Leavy O. The good the gut bugs do[J]. Nat Rev Immunol, 2012, 12(5): 319. doi:10.1038/nri3213
[5] Rentier C, Pacini G, Nuti F, et al. Synthesis of diastereomerically pure Lys(N ε-lipoyl)building blocks and their use in Fmoc/tBu solid phase synthesis of lipoyl-containing peptides for diagnosis of primary biliary cirrhosis[J]. J Pept Sci, 2015, 21(5): 408-414. doi:10.1002/psc.2761
[6] Flores A, Mayo MJ. Primary biliary cirrhosis in 2014[J].Curr Opin Gastroenterol, 2014,30(3):245-252. doi:10.1097/MOG.0000000000000058
[7] Wang LF, Sun Y, Zhang Z, et al. CXCR5⁺ CD4⁺ T follicular helper cells participate in the pathogenesis of primary biliary cirrhosis[J]. Hepatology, 2015, 61(2): 627-638. doi:10.1002/hep.27306
[8] Takahashi T, Miura T, Nakamura J, et al. Plasma cells and the chronic nonsuppurative destructive cholangitis of primary biliary cirrhosis[J]. Hepatology, 2012, 55(3): 846-855. doi:10.1002/hep.24757
[9] Zimmermann P, Messina N, Mohn WW, et al. Association between the intestinal microbiota and allergic sensitization, eczema, and asthma: a systematic review[J]. J Allergy Clin Immunol, 2019, 143(2): 467-485. doi:10.1016/j.jaci.2018.09.025
[10] Zou QY, Hong SL, Kang HY, et al. Effect of di-(2-ethylhexyl)phthalate(DEHP)on allergic rhinitis[J]. Sci Rep, 2020, 10(1): 14625. doi:10.1038/s41598-020-71517-6
[11] Le Lay S, Boucher J, Rey A, et al. Decreased resistin expression in mice with different sensitivities to a high-fat diet[J]. Biochem Biophys Res Commun, 2001, 289(2): 564-567. doi:10.1006/bbrc.2001.6015
[12] Liu CS, Zhao DF, Ma WJ, et al. Denitrifying sulfide removal process on high-salinity wastewaters in the presence of Halomonas sp[J]. Appl Microbiol Biotechnol, 2016, 100(3): 1421-1426. doi:10.1007/s00253-015-7039-6
[13] Chen SF, Zhou YQ, Chen YR, et al. Fastp: an ultra-fast all-in-one FASTQ preprocessor[J]. Bioinformatics, 2018, 34(17): i884-i890. doi:10.1093/bioinformatics/bty560
[14] Mago c T, Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies[J]. Bioinformatics, 2011, 27(21): 2957-2963. doi:10.1093/bioinformatics/btr507
[15] Edgar RC. UPARSE: highly accurate OTU sequences from microbial amplicon reads[J]. Nat Methods, 2013, 10(10): 996-998. doi:10.1038/nmeth.2604
[16] Wang Q, Garrity GM, Tiedje JM, et al. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy[J]. Appl Environ Microbiol, 2007, 73(16): 5261-5267. doi:10.1128/AEM.00062-07
[17] Douglas GM, Maffei VJ, Zaneveld JR, et al. PICRUSt2 for prediction of metagenome functions[J]. Nat Biotechnol, 2020, 38(6): 685-688. doi:10.1038/s41587-020-0548-6
[18] Schloss PD, Westcott SL, Ryabin T, et al. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities[J]. Appl Environ Microbiol, 2009, 75(23): 7537-7541. doi:10.1128/AEM.01541-09
[19] Segata N, Izard J, Waldron L, et al. Metagenomic biomarker discovery and explanation[J]. Genome Biol, 2011, 12(6): R60. doi:10.1186/gb-2011-12-6-r60
[20] Long HY. Esculetin attenuates Th2 and Th17 responses in an ovalbumin-induced asthmatic mouse model[J]. Inflammation, 2016, 39(2): 735-743. doi:10.1007/s10753-015-0300-4
[21] Walters SN, Webster KE, Daley S, et al. A role for intrathymic B cells in the generation of natural regulatory T cells[J]. J Immunol, 2014, 193(1): 170-176. doi:10.4049/jimmunol.1302519
[22] Bárcena C, Valdés-Mas R, Mayoral P, et al. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice[J]. Nat Med, 2019, 25(8): 1234-1242. doi:10.1038/s41591-019-0504-5
[23] Guan WJ, Yuan JJ, Li HM, et al. Proteobacteria community compositions correlate with bronchiectasis severity[J]. Int J Tuberc Lung Dis, 2018, 22(9): 1095-1105. doi:10.5588/ijtld.18.0037
[24] Mainz RE, Albers S, Haque M, et al. NLRP6 inflammasome modulates disease progression in a chronic-plus-binge mouse model of alcoholic liver disease[J]. Cells, 2022, 11(2): 182. doi:10.3390/cells11020182
[25] 林小燕, 李静, 马志祺, 等. 益生菌治疗变应性鼻炎的临床疗效及抗变态反应作用Meta分析[J]. 山东大学耳鼻喉眼学报, 2021, 35(3): 70-80. doi:10.6040/j.issn.1673-3770.0.2020.374 LIN Xiaoyan, LI Jing, MA Zhiqi, et al. Therapeutic and anti-allergic effects of probiotics on allergic rhinitis: a meta-analysis[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(3): 70-80. doi:10.6040/j.issn.1673-3770.0.2020.374
[26] Netto Candido TL, Bressan J, Alfenas RCG. Dysbiosis and metabolic endotoxemia induced by high-fat diet[J]. Nutr Hosp, 2018, 35(6): 1432-1440. doi: 10.20960/nh.1792
[27] Kim KA, Gu W, Lee IA, et al. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway[J]. PLoS One, 2012, 7(10): e47713. doi:10.1371/journal.pone.0047713
[28] Devkota S, Wang YW, Musch MW, et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in IL-10^{-/ -} mice[J]. Nature, 2012, 487(7405): 104-108. doi:10.1038/nature11225
[29] Caesar R, Tremaroli V, Kovatcheva-Datchary P, et al. Crosstalk between gut Microbiota and dietary lipids aggravates WAT inflammation through TLR signaling[J]. Cell Metab, 2015, 22(4): 658-668. doi:10.1016/j.cmet.2015.07.026
[30] Wang RQ, Yang XY, Liu JT, et al. Gut microbiota regulates acute myeloid leukaemia via alteration of intestinal barrier function mediated by butyrate[J]. Nat Commun, 2022, 13(1): 2522. doi:10.1038/s41467-022-30240-8
[31] Koeth RA, Lam-Galvez BR, Kirsop J, et al. L-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans[J]. J Clin Invest, 2019, 129(1): 373-387. doi:10.1172/JCI94601
[32] Koeth RA, Wang ZN, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis[J]. Nat Med, 2013, 19(5): 576-585. doi:10.1038/nm.3145
[33] Janeiro MH, Ramírez MJ, Milagro FI, et al. Implication of trimethylamine N-oxide(TMAO)in disease: potential biomarker or new therapeutic target[J]. Nutrients, 2018, 10(10): E1398. doi:10.3390/nu10101398
[34] Chen K, Zheng XQ, Feng MC, et al. Gut Microbiota-dependent metabolite trimethylamine N-oxide contributes to cardiac dysfunction in western diet-induced obese mice[J]. Front Physiol, 2017, 8: 139. doi:10.3389/fphys.2017.00139
[35] Rohrmann S, Linseisen J, Allenspach M, et al. Plasma concentrations of trimethylamine-N-oxide are directly associated with dairy food consumption and low-grade inflammation in a German adult population[J]. J Nutr, 2016, 146(2): 283-289. doi:10.3945/jn.115.220103

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