Exploring the Beneficial Effects of Guangxi Longevity Dietary Patterns on Human Body Based on Metabolomics
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摘要: 为了深入探究饮食与机体健康状态的关系,本研究试图从代谢组学的角度,评估所构建的广西长寿饮食模式对人体的有益影响。筛选志愿者在经过2周习惯性饮食后,高依从性地遵循这种饮食模式2周,在习惯性饮食前,广西长寿饮食前(习惯性饮食后)和广西长寿饮食后3次分别采集志愿者的血液和粪便样品,进行代谢组学分析。归纳所得结果发现,广西长寿饮食干预后志愿者血清组氨酸、甘油、α-葡萄糖和β-葡萄糖相对丰度显著增加(P<0.05),胆碱和乳酸的相对丰度显著降低(P<0.05)。此外还发现,粪便中的乙酸盐和丁酸盐含量显著上升(P<0.05)。代谢物组富集分析和途径分析结果表明,这些代谢物的变化可能与糖酵解/糖异生途径、丙酮酸代谢和半乳糖代谢3条途径密切相关。通过对差异代谢物的分析,认为广西长寿饮食模式对改善机体炎症水平、调节机体健康状态、预防机体罹患心血管疾病具有一定的作用。上述结果也从代谢组学角度对饮食促进机体健康长寿的关系提供了一定机制方面的阐释。
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关键词:
- 饮食模式 /
- 益生效果 /
- 代谢组学 /
- 核磁共振氢谱(1H NMR) /
- 气相色谱-质谱法(GC-MS) /
- 短链脂肪酸(SCFAs)
Abstract: To explore the relationship between diet and human health, this study aimed to evaluate the beneficial effects of the existing Guangxi longevity dietary pattern on the human body from metabolomics. After 2 weeks of habitual diet, the selected volunteers followed this dietary pattern with high adherence for the same period. The blood and fecal samples were collected 3 times then performed metabolomics analysis, including before the habitual diet, the beginning (which was also the ending point of habitual diet) and the end of Guangxi longevity dietary pattern. The results showed that after the Guangxi longevity dietary intervention of volunteers, the relative abundance of serum histidine, glycerol, α-glucose and β-glucose was significantly increased (P<0.05), but the relative richness of choline and lactic acid reduced obviously (P<0.05). In addition, the fecal acetate and butyrate increased apparently (P<0.05). Moreover, the analysis of metabolome enrichment and pathway revealed that these metabolites' variations might be closely related to three pathways, including glycolysis/gluconeogenesis pathway, pyruvate metabolism, and galactose metabolism. Through the analysis of differential metabolites, it was considered that Guangxi longevity dietary pattern played a promoted role in improving the level of inflammation, regulating the health status and preventing the organism from developing cardiovascular diseases. The above results also provide a mechanical explanation of the relationship between dietary patterns and healthy longevity from human metabolism. -
图 2 志愿者习惯性饮食阶段和广西长寿饮食阶段的代表性CPMG 1H NMR血清光谱
Figure 2. Typical 500 MHz 1H NMR spectra of serum extracts for the volunteer with habitual diet and Guangxi longevity dietary
注:与δ0.5~4.6相比,δ5.0~.4区域的光谱垂直扩大了6倍。1.脂质;2.异亮氨酸;3.亮氨酸;4.缬氨酸;5.乙醇;6.乳酸;7.丙氨酸;8.赖氨酸;9.乙酸;10.N-乙酰糖蛋白;11.谷氨酰胺;12.蛋氨酸;13.丙酮;14.乙酰乙酸盐;15.柠檬酸;16.三甲胺;17.肌酐;18. N-亚硝基二甲胺;19.胆碱;20.磷酸胆碱;21.三甲胺-N-氧化物;22.脯氨酸;23.鲨肌醇;24.甘氨酸;25.甘油;26.丝氨酸;27.苏氨酸;28. β-葡萄糖;29.α-葡萄糖;30.不饱和脂肪酸;31.组氨酸;32.酪氨酸;33.丙酮酸。
表 1 基线时志愿者临床和人口统计学特征
Table 1. Clinical and demographic characteristics of volunteers at baseline
基线特征 参数 年龄(岁) 62.93±9.36 性别(男/女) 7/7 BMI(kg/m2) 25.42±3.75 表 2 血清中主要代谢物的统计分析结果
Table 2. Statistical analysis results of the main metabolite in serum
代谢物
(出峰位置)VIP 相对丰度 P值 习惯性饮食 广西长寿饮食 α-葡萄糖(5.23 ppm) 1.15 1.41±0.29 1.65±0.25↑ 0.005 β-葡萄糖(3.90 ppm) 1.65 2.53±0.50 3.00±0.45↑ 0.006 β-葡萄糖(3.43 ppm) 2.92 8.51±1.68 10.04±1.65↑ 0.005 α-葡萄糖/β-葡萄糖
(3.68~3.79 ppm)2.14 7.76±1.16 8.74±1.44↑ 0.008 组氨酸(3.25 ppm) 1.37 2.32±0.57 2.73±0.57↑ 0.017 胆碱(3.20 ppm) 2.60 5.54±1.59 4.23±1.57↓ 0.015 N-乙酰糖蛋白
(2.03 ppm)1.07 3.75±1.06 4.19±1.13↑ 0.053 脂质(1.28 ppm) 2.95 23.69±7.44 20.76±5.30↓ 0.086 乳酸(4.11 ppm) 1.16 1.85±0.55 1.54±0.38↓ 0.004 乳酸(1.33 ppm) 2.33 6.76±2.12 5.54±1.22↓ 0.017 甘油(3.65 ppm) 1.78 2.01±0.79 2.67±0.90↑ 0.020 注:↑表示与习惯性饮食相比,在广西长寿饮食干预后代谢物相对丰度显著升高(P<0.05);↓表示与习惯性饮食相比,在广西长寿饮食干预后代谢物相对丰度有所降低(P<0.05)。 表 3 粪便SCFAs的统计分析结果
Table 3. Statistical analysis results of the main SCFAs in feces
SCFAs 相对含量(mmol/L) P值 Day 0 Day 15 Day 29 Day 15 vs. Day 0 Day 15 vs. Day 29 乙酸 30.03±5.49 30.40±6.65 37.64±4.90↑ 0.826 0.005 丙酸 12.18±4.39 12.34±7.25 13.58±3.88 0.730 0.221 异丁酸 1.22±0.60 1.32±0.43 1.78±0.96 0.347 0.445 丁酸 15.63±6.62 15.43±5.13 24.51±7.02↑ 0.683 0.004 异戊酸 1.17±0.68 1.15±0.56 1.54±1.26 0.701 0.552 戊酸 0.98±0.46 1.05±0.57 1.55±1.08 0.382 0.101 注:↑表示与Day15(广西长寿饮食干预前)相比,Day29(广西长寿饮食干预后)SCFAs相对含量显著上升(P<0.05)。 -
[1] KE C, XU H, CHEN Q, et al. Serum metabolic signatures of high myopia among older Chinese adults[J]. Eye,2021,35(3):817−824. doi: 10.1038/s41433-020-0968-z [2] FLOEGEL A, STEFAN N, YU Z, et al. Identification of serum metabolites associated with risk of Type 2 diabetes using a targeted metabolomic approach[J]. Diabetes,2013,62(2):639−648. doi: 10.2337/db12-0495 [3] ZHANG Y, ZHANG H, CHANG D, et al. Metabolomics approach by 1 H NMR spectroscopy of serum reveals progression axes for asymptomatic hyperuricemia and gout[J]. Arthritis Res Ther,2018,20(1):111. doi: 10.1186/s13075-018-1600-5 [4] RAWAT A, MISRA G, SAXENA M, et al. (1)H NMR based serum metabolic profiling reveals differentiating biomarkers in patients with diabetes and diabetes-related complication[J]. Diabetes Metab Syndr,2019,13(1):290−298. doi: 10.1016/j.dsx.2018.09.009 [5] 朱莹莹, 李春保, 周光宏. 饮食、肠道微生物与健康的关系研究进展[J]. 食品科学,2015,36(15):234−239. [ZHU Y Y, LI C B, ZHOU G H. Advances in the associations of diet with gut microbiota and human health[J]. Food Science,2015,36(15):234−239. doi: 10.7506/spkx1002-6630-201515043ZHU Y Y, LI C B, ZHOU G H. Advances in the associations of diet with gut microbiota and human health[J]. Food Science, 2015, 36(15): 234-239. doi: 10.7506/spkx1002-6630-201515043 [6] REEDY J, KREBS-SMITH S M, MILLER P E, et al. Higher diet quality is associated with decreased risk of all-cause, cardiovascular disease, and cancer mortality among older adults[J]. J Nutr,2014,144(6):881−889. doi: 10.3945/jn.113.189407 [7] ARCHUNDIA HERRERA M C, SUBHAN F B, CHAN C B. Dietary patterns and cardiovascular disease risk in people with Type 2 diabetes[J]. Current Obesity Reports,2017,6(4):405−413. doi: 10.1007/s13679-017-0284-5 [8] MATSUYAMA S, ZHANG S, TOMATA Y, et al. Association between improved adherence to the Japanese diet and incident functional disability in older people: The Ohsaki Cohort 2006 study[J]. Clinical Nutrition, 2019, 39(7). [9] HU E A, CORESH J, ANDERSON C, et al. Adherence to healthy dietary patterns and risk of CKD progression and all-cause mortality: Findings from the CRIC (Chronic Renal Insufficiency Cohort) study[J]. American Journal of Kidney Diseases, 2020. [10] MICHALCZYK M M, KLONEK G, MASZCZYK A, et al. The effects of a low calorie ketogenic diet on glycaemic control variables in hyperinsulinemic overweight/obese females[J]. Nutrients,2020,12(6):1854. doi: 10.3390/nu12061854 [11] PASANISI P, GARIBOLDI M, VERDERIO P, et al. A pilot low-inflammatory dietary intervention to reduce inflammation and improve quality of life in patients with familial adenomatous polyposis: Protocol description and preliminary results[J]. 2019, 18(11): 153473541984640. [12] POLL B G, CHEEMA M U, PLUZNICK J L. Gut microbial metabolites and blood pressure regulation: Focus on SCFAs and TMAO[J]. Physiology (Bethesda),2020,35(4):275−284. [13] 蔡达. 广西长寿之乡老人饮食与代谢特征及其相关性研究[D]. 南宁: 广西大学, 2017.CAI D. A correlation between diet and metabolic characteristics of healthy elderly people from longevous region in Guangxi province[D]. Nanning: Guangxi University, 2017. [14] 宋奇, 艾连中, 鲁红岩, 等. 巴马长寿饮食模式在衰老小鼠模型中的抗氧化应激效果[J]. 食品科学,2018,39(19):147−153. [SONG Q, AI L Z, LU H Y, et al. Effect of Bama longevity dietary patterns on antioxidant stress in a mouse model of aging[J]. Food Science,2018,39(19):147−153. doi: 10.7506/spkx1002-6630-201819023SONG Q, AI L Z, LU H Y, et al. Effect of Bama longevity dietary patterns on antioxidant stress in a mouse model of aging[J]. Food Science, 2018, 39(19): 147-153. doi: 10.7506/spkx1002-6630-201819023 [15] 黄燕婷, 梅丽华, 潘海博, 等. 巴马长寿特征饮食模式对自然衰老小鼠的抗衰老效果[J]. 食品科学,2021,42(5):137−144. [HUANG Y T, MEI L H, PAN H B, et al. Anti-aging effect of Bama longevity characteristic dietary patterns in naturally aging mice[J]. Food Science,2021,42(5):137−144. doi: 10.7506/spkx1002-6630-20200229-328HUANG Y T, MEI L H, PAN H B, et al. Anti-aging effect of Bama longevity characteristic dietary patterns in naturally aging mice[J]. Food Science, 2021, 42(5): 137-144. doi: 10.7506/spkx1002-6630-20200229-328 [16] 祁波, 谢辉辉, 李国芳, 等. 金欣口服液对呼吸道合胞病毒诱发支气管哮喘模型小鼠血浆短链脂肪酸的影响[J]. 中医儿科杂志,2021,17(4):11−17. [QI B, XIE H H, LI G F, et al. Effects of Jinxin Koufuye on plasma short-chain fatty acids in respiratory syncytial virus-induced bronchial asthma in model mice[J]. Journal of Pediatrics of Traditional Chinese Medicine,2021,17(4):11−17.QI B, XIE H H, LI G F, et al. Effects of Jinxin Koufuye on plasma short-chain fatty acids in respiratory syncytial virus-induced bronchial asthma in model mice[J]. Journal of Pediatrics of Traditional Chinese Medicine, 2021, 17(4): 11-17. [17] BRONS C, SPOHR C, STORGAARD H, et al. Effect of taurine treatment on insulin secretion and action, and on serum lipid levels in overweight men with a genetic predisposition for Type II diabetes mellitus[J]. Eur J Clin Nutr,2004,58(9):1239−1247. doi: 10.1038/sj.ejcn.1601955 [18] BROSKEY N T, ZOU K, DOHM G L, et al. Plasma lactate as a marker for metabolic health[J]. Exercise and Sport Sciences Reviews,2020,48(3):119−124. [19] DU S, SUN S, LIU L, et al. Effects of histidine supplementation on global serum and urine (1)H NMR-based metabolomics and serum amino acid profiles in obese women from a randomized controlled study[J]. J Proteome Res,2017,16(6):2221−2230. doi: 10.1021/acs.jproteome.7b00030 [20] HTUN K T, PAN J, PASANTA D, et al. Identification of metabolic phenotypes in young adults with obesity by (1)H NMR metabolomics of blood serum[J]. Life (Basel), 2021, 11(6). [21] CAMPOS-PEREZ W, MARTINEZ-LOPEZ E. Effects of short chain fatty acids on metabolic and inflammatory processes in human health[J]. Biochim Biophys Acta Mol Cell Biol Lipids,2021,1866(5):158900. [22] DAVID L A, MAURICE C F, CARMODY R N, et al. Diet rapidly and reproducibly alters the human gut microbiome[J]. Nature,2014,505(7484):559−563. doi: 10.1038/nature12820 [23] BRÜSSOW H, PARKINSON S J. You are what you eat[J]. Nature Biotechnology,2014,32(3):243−245. doi: 10.1038/nbt.2845 [24] PALVIAINEN M, LAUKKANEN K, TAVUKCUOGLU Z, et al. Cancer alters the metabolic fingerprint of extracellular vesicles[J]. Cancers (Basel), 2020, 12(11). [25] WARE L J, RENNIE K L, KRUGER H S, et al. Evaluation of waist-to-height ratio to predict 5 year cardiometabolic risk in sub-Saharan African adults[J]. Nutr Metab Cardiovasc Dis,2014,24(8):900−907. doi: 10.1016/j.numecd.2014.02.005 [26] WHITE E S, XIA M, MURRAY S, et al. Plasma surfactant protein-D, matrix metalloproteinase-7, and osteopontin index distinguishes idiopathic pulmonary fibrosis from other idiopathic interstitial pneumonias[J]. Am J Respir Crit Care Med,2016,194(10):1242−1251. doi: 10.1164/rccm.201505-0862OC [27] KOUIDHI S, ZIDI O, ALHUJAILY M, et al. Fecal metabolomics reveals distinct profiles of kidney transplant recipients and healthy controls[J]. Diagnostics (Basel), 2021, 11(5). [28] BRISSON D, VOHL M C, PIERRE S T J, et al. Glycerol: A neglected variable in metabolic processes?[J]. BioEssays,2001,23(6):534−452. doi: 10.1002/bies.1073 [29] 周小理, 张欢, 周一鸣, 等. 基于代谢组学研究苦荞蛋白对高脂血症小鼠的干预作用[J]. 食品科学,2019,40(5):149−155. [ZHOU X L, ZHANG H, ZHOU Y M, et al. Metabonomic Study of the intervention effect of tartary buckwheat protein on hyperlipidemic mice[J]. Food Science,2019,40(5):149−155. doi: 10.7506/spkx1002-6630-20171030-354ZHOU X L, ZHANG H, ZHOU Y M, et al. Metabonomic Study of the intervention effect of tartary buckwheat protein on hyperlipidemic mice[J]. Food Science, 2019, 40(5): 149-155. doi: 10.7506/spkx1002-6630-20171030-354 [30] KIM Y, KIM Y. L-histidine and L-carnosine exert anti-brain aging effects in D-galactose-induced aged neuronal cells[J]. Nutr Res Pract,2020,14(3):188−202. doi: 10.4162/nrp.2020.14.3.188 [31] FENG R N, NIU Y C, SUN X W, et al. Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: A randomised controlled trial[J]. Diabetologia,2013,56(5):985−994. doi: 10.1007/s00125-013-2839-7 [32] COOPERMAN J M, LOPEZ R. The role of histidine in the anemia of folate deficiency[J]. Experimental biology and medicine (Maywood, N J),2002,227(11):998−1000. doi: 10.1177/153537020222701107 [33] HEFNI M E, WITTHÖFT C M, MOAZZAMI A A. Plasma metabolite profiles in healthy women differ after intervention with supplemental folic acid v. folate-rich foods[J]. Journal of Nutritional Science,2018,7:e32. doi: 10.1017/jns.2018.22 [34] NIU Y C, FENG R N, HOU Y, et al. Histidine and arginine are associated with inflammation and oxidative stress in obese women[J]. Br J Nutr,2012,108(1):57−61. doi: 10.1017/S0007114511005289 [35] ADEVA-ANDANY M, LÓPEZ-OJÉN M, FUNCASTA-CALDERÓN R, et al. Comprehensive review on lactate metabolism in human health[J]. Mitochondrion,2014,17:76−100. doi: 10.1016/j.mito.2014.05.007 [36] SCHMEDES M, BALDERAS C, AADLAND E K, et al. The effect of lean-seafood and non-seafood diets on fasting and postprandial serum metabolites and lipid species: Results from a randomized crossover intervention study in healthy adults[J]. Nutrients, 2018, 10(5): 598. [37] XU J, LIU C, CAI S, et al. Metabolomic profilings of urine and serum from high fat-fed rats via 1h nmr spectroscopy and pattern recognition[J]. Applied Biochemistry and Biotechnology,2013,169(4):1250−1261. doi: 10.1007/s12010-012-0072-3 [38] CASTAGNARO S, PELLEGRINI C, PELLEGRINI M, et al. Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial[J]. Autophagy,2016,12(12):2484−2495. doi: 10.1080/15548627.2016.1231279 [39] BOUZIER-SORE A K, VOISIN P, BOUCHAUD V, et al. Competition between glucose and lactate as oxidative energy substrates in both neurons and astrocytes: A comparative NMR study[J]. European Journal of Neuroscience,2006,24(6):1687−1694. doi: 10.1111/j.1460-9568.2006.05056.x [40] GRAY L R, TOMPKINS S C, TAYLOR E B. Regulation of pyruvate metabolism and human disease[J]. Cellular and Molecular Life Sciences,2014,71(14):2577−2604. doi: 10.1007/s00018-013-1539-2 [41] KONSTANTINOVA S V, TELL G S, VOLLSET S E, et al. Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women[J]. The Journal of Nutrition,2008,138(5):914−920. doi: 10.1093/jn/138.5.914 [42] GUERTIN K A, LI X S, GRAUBARD B I, et al. Serum trimethylamine N-oxide, carnitine, choline, and betaine in relation to colorectal cancer risk in the alpha tocopherol, beta carotene cancer prevention study[J]. Cancer Epidemiol Biomarkers Prev,2017,26(6):945−952. doi: 10.1158/1055-9965.EPI-16-0948 [43] HEIANZA Y, SUN D, SMITH S R, et al. Changes in gut microbiota–related metabolites and long-term successful weight loss in response to weight-loss diets: The pounds lost trial[J]. Diabetes Care,2018,41(3):413−419. doi: 10.2337/dc17-2108 [44] PENG J, XIAO X, HU M, et al. Interaction between gut microbiome and cardiovascular disease[J]. Life Sci,2018,214:153−157. doi: 10.1016/j.lfs.2018.10.063 [45] ABBASALIZAD FARHANGI M, VAJDI M. Gut microbiota-associated trimethylamine N-oxide and increased cardiometabolic risk in adults: A systematic review and dose-response meta-analysis[J]. Nutr Rev,2021,79(9):1022−1042. doi: 10.1093/nutrit/nuaa111 [46] 高中山, 任明, 刘杏利, 等. 短链脂肪酸在冠心病防治中的研究进展[J]. 临床心血管病杂志,2021,37(11):1062−1066. [GAO Z S, REN M, LIU X L, et al. Research progress on short chain fatty acids in prevention and treatment of coronary heart disease[J]. Journal of Clinical Cardiology,2021,37(11):1062−1066.GAO Z S, REN M, LIU X L, et al. Research progress on short chain fatty acids in prevention and treatment of coronary heart disease[J]. Journal of Clinical Cardiology, 2021, 37(11): 1062-1066. [47] AGUILAR E C, LEONEL A J, TEIXEIRA L G, et al. Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NFκB activation[J]. Nutrition, Metabolism and Cardiovascular Diseases,2014,24(6):606−613. doi: 10.1016/j.numecd.2014.01.002 [48] ROSHANRAVAN N, MAHDAVI R, ALIZADEH E, et al. Effect of butyrate and inulin supplementation on glycemic status, lipid profile and glucagon-like peptide 1 level in patients with Type 2 diabetes: A randomized double-blind, placebo-controlled trial[J]. Horm Metab Res,2017,49(11):886−891. doi: 10.1055/s-0043-119089 [49] PAPARO L, CALIGNANO A, TOCCHETTI C G, et al. The influence of fiber on gut microbiota: Butyrate as molecular player involved in the beneficial interplay between dietary fiber and cardiovascular health[M]. Dietary Fiber for the Prevention of Cardiovascular Disease, 2017: 61−71. [50] QUERCIA S, TURRONI S, FIORI J, et al. Gut microbiome response to short-term dietary interventions in reactive hypoglycemia subjects[J]. Diabetes/Metabolism Research and Reviews,2017,33(8):e2927. [51] JEE S H, OHRR H, SULL J W, et al. Fasting serum glucose level and cancer risk in korean men and women[J]. JAMA,2005,293(2):194−202. doi: 10.1001/jama.293.2.194 [52] SOTO-HEREDERO G, GOMEZ DE LAS HERAS M M, GABANDE-RODRIGUEZ E, et al. Glycolysis-a key player in the inflammatory response[J]. Febs J,2020,287(16):3350−3369. doi: 10.1111/febs.15327 [53] FU Y, YIN R, LIU Z, et al. Hypoglycemic effect of prolamin from cooked foxtail millet (Setaria italic) on streptozotocin-induced diabetic mice[J]. Nutrients, 2020, 12(11): 3452. -