鲜天麻提取物对小鼠肠道菌群结构的影响
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摘要
天麻Gastrodia elata Bl.作为传统中药,具有息风止痉,平抑肝阳,祛风通络的功效,常用于治疗头痛、偏头痛等神经系统疾病,已被提议加入"按照传统既是食品又是中药材物质的目录"。临床常用干天麻的药效及作用机制已有相应的研究基础。而鲜天麻作为保健药膳的常用原料目前还缺乏研究。近年来饮食-肠道菌群-宿主的相互作用,及其对维护人体健康的影响已引起关注。目前已发现许多药食两用物质都可以通过调节肠道菌群维护人体健康。该研究利用MiSeq平台对服用鲜天麻提取物的小鼠盲肠内容物进行16S rRNA测序,探究鲜天麻提取物对小鼠肠道菌群结构的影响。结果表明,天麻提取物可显著提高小鼠肠道菌的益生菌属如Ruminiclostridium,Butyricicoccus,Parvibacter的丰度;而致病菌和条件致病菌属如Escherichia/Shigella,Parasutterella等丰度下降,说明长期服用鲜天麻对小鼠肠道菌群具有一定的调节作用,其中低剂量鲜天麻提取物能够显著调节肠道菌群结构。该研究结果揭示了肠道菌群可能是天麻提取物新的作用靶点,为后期探究天麻的药理作用与肠道菌群间的关系以及作为提供了重要基础
Gastrodia elata B1.,a traditional Chinese medicine,was frequently applied as a cure for headache or migraine. Its effects include suppressing hyperactive liver,calming endogenous wind,dredging collateralsand relieving spasm. There has been a proportion that G. elata should be added to The List of Substances That Are Traditionally Both Food and Chinese Medicinal Materials. The dry G. elata was commonly used in clinic,which have some fundamental study on efficacy and mechanism. However,fresh G. elata,which was added to herbal cuisine very often,lacks corresponding research. The interaction of diet,microbiota and human is a hot issue and lots of scholars are focusing on it. This research sequenced the 16 S rRNA of mouse cecal contents on Mi Seq platform to understand the effect of taking fresh G. elata. As the results showing,multiple probiotics grew after taking fresh G. elata extract,including Ruminiclostridium,Butyricicoccus,and Parvibacter. To contrast,some pathogens or potential pathogens,such as Escherichia/Shigella,Parasutterella,decreased. This manifests that fresh G. elata performs a positive regulation on mouse gut microbiota,especially the low-dose fresh G. elata extraction could restructure the microbiota apparently. Our result reveals that microbiota might be a new target for G. elata extract and provides an important basis for further research on the interaction between gut microbiota and pharmacological activity of G. elata.
Gastrodia elata B1.,a traditional Chinese medicine,was frequently applied as a cure for headache or migraine. Its effects include suppressing hyperactive liver,calming endogenous wind,dredging collateralsand relieving spasm. There has been a proportion that G. elata should be added to The List of Substances That Are Traditionally Both Food and Chinese Medicinal Materials. The dry G. elata was commonly used in clinic,which have some fundamental study on efficacy and mechanism. However,fresh G. elata,which was added to herbal cuisine very often,lacks corresponding research. The interaction of diet,microbiota and human is a hot issue and lots of scholars are focusing on it. This research sequenced the 16 S rRNA of mouse cecal contents on Mi Seq platform to understand the effect of taking fresh G. elata. As the results showing,multiple probiotics grew after taking fresh G. elata extract,including Ruminiclostridium,Butyricicoccus,and Parvibacter. To contrast,some pathogens or potential pathogens,such as Escherichia/Shigella,Parasutterella,decreased. This manifests that fresh G. elata performs a positive regulation on mouse gut microbiota,especially the low-dose fresh G. elata extraction could restructure the microbiota apparently. Our result reveals that microbiota might be a new target for G. elata extract and provides an important basis for further research on the interaction between gut microbiota and pharmacological activity of G. elata.
引文
[1] Zhan H D,Zhou H Y,Sui Y P,et al. The rhizome of Gastrodia elata Blume-an ethnopharmacological review[J]. J Ethnopharmacol,2016,189:361.
[2] Matias M,Silvestre S,Falcao A,et al. Gastrodia elata and epilepsy:rationale and therapeutic potential[J]. Phytomedicine,2016,23(12):1511.
[3] Zhang J S,Zhou S F,Wang Q,et al. Gastrodin suppresses BACE1 expression under oxidative stress condition via inhibition of the PKR/e IF2alpha pathway in Alzheimer's disease[J]. Neuroscience,2016,325:1.
[4] Huang J Y,Yuan Y H,Yan J Q,et al. 20C,a bibenzyl compound isolated from Gastrodia elata,protects PC12 cells against rotenone-induced apoptosis via activation of the Nrf2/ARE/HO-1signaling pathway[J]. Acta Pharmacol Sin,2016,37(6):731.
[5] Duparc T,Plovier H,Marrachelli V G,et al. Hepatocyte My D88affects bile acids,gut microbiota and metabolome contributing to regulate glucose and lipid metabolism[J]. Gut, 2017, 66(4):620.
[6] Utzschneider K M,Kratz M,Damman C J,et al. Mechanisms linking the gut microbiome and glucose metabolism[J]. J Clin Endocrinol Metab,2016,101(4):1445.
[7]孙艺凡,张霞,王晓艳,等.长期服用人参提取物对大鼠肠道菌群结构的影响[J].中国中药杂志,2018,43(19):3927.
[8] Mayer E A,Knight R,Mazmanian S K,et al. Gut microbes and the brain:paradigm shift in neuroscience[J]. J Neurosci,2014,34(46):15490.
[9] Magoc T,Salzberg S L. FLASH:fast length adjustment of short reads to improve genome assemblies[J]. Bioinformatics,2011,27(21):2957.
[10] Edgar R C. Search and clustering orders of magnitude faster than BLAST[J]. Bioinformatics,2010,26(19):2460.
[11] Caporaso J G,Kuczynski J,Stombaugh J,et al. QIIME allows analysis of high-throughput community sequencing data[J]. Nat Methods,2010,7(5):335.
[12] Segata N,Izard J,Waldron L,et al. Metagenomic biomarker discovery and explanation[J]. Genome Biol,2011,12(6):R60.
[13] Langille M G,Zaneveld J,Caporaso J G,et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences[J]. Nat Biotechnol,2013,31(9):814.
[14] Han Y J,Je J H,Kim S H,et al. Gastrodia elata shows neuroprotective effects via activation of PI3K signaling against oxidative glutamate toxicity in HT22 cells[J]. Am J Chin Med,2014,42(4):1007.
[15] Chen W C,Lai Y S,Lin S H,et al. Anti-depressant effects of Gastrodia elata Blume and its compounds gastrodin and4-hydroxybenzyl alcohol,via the monoaminergic system and neuronal cytoskeletal remodeling[J]. J Ethnopharmacol,2016,182:190.
[16]刘娜,张振兴,马金刚,等.天麻素药代动力学和组织分布特征研究[J].药物分析杂志,2015,35(8):1369.
[17] Zhang W,Sheng Y X,Zhang J L. Determination and pharmacokinetics of gastrodin and p-hydroxybenzylalcohol after oral administration of Gastrodia elata Bl. extract in rats by high-performance liquid chromatography-electrospray ionization mass spectrometric method[J]. Phytomedicine,2008,15(10):844.
[18]杨飞,王信,马传江,等.天麻加工炮制、成分分析与体内代谢研究进展[J].中国中药杂志,2018,43(11):2207.
[19] Turnbaugh P J,Backhed F,Fulton L,et al. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome[J]. Cell Host Microbe, 2008, 3(4):213.
[20] Turnbaugh P J,Ley R E,Mahowald M A,et al. An obesity-associated gut microbiome with increased capacity for energy harvest[J]. Nature,2006,444(7122):1027.
[21] Xiao S,Fei N,Pang X,et al. A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome[J]. FEMS Microbiol Ecol, 2014, 87(2):357.
[22] Tomova A,Husarova V,Lakatosova S,et al. Gastrointestinal microbiota in children with autism in Slovakia[J]. Physiol Behav,2015,138:179.
[23] Kang D W,Admas J B,Gregory A C,et al. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms:an open-label study[J]. Microbiome,2017,5(1):10.
[24] Zhang-Sun W,Augsto L A,Zhao L,et al. Desulfovibrio desulfuricans isolates from the gut of a single individual:structural and biological lipid A characterization[J]. FEBS Lett,2015,589(1):165.
[25] Yin J,Liao S X,He Y,et al. Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with largeartery atherosclerotic stroke or transient ischemic attack[J]. J Am Heart Assoc,2015,4(11):e002699.
[26] Chiodin R J,Dowd S E,Chamberlin W M,et al. Microbial population differentials between mucosal and submucosal intestinal tissues in advanced crohn's disease of the ileum[J]. PLoS ONE,2015,10(7):e0134382.
[27] Chen Y J,Wu H,Wu S D,et al. Parasutterella,in association with irritable bowel syndrome and intestinal chronic inflammation[J]. J Gastroenterol Hepatol,2018,33(11):1844.
[28] Zhao L,Zhang Q,Ma W,et al. A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota[J]. Food Funct,2017,8(12):4644.
[29] Eeckhaut V,Machiels K,Perrier C,et al. Butyricicoccus pullicaecorum in inflammatory bowel disease[J]. Gut,2013,62(12):1745.
[30] Fujio-Vejar S,Vasquez Y,Morales P,et al. The gut microbiota of healthy chilean subjects reveals a high abundance of the phylum verrucomicrobia[J]. Front Microbiol,2017,8:1221.
[31] Geirnaer A,Steyaert A,Eeckhaut V,et al. Butyricicoccus pullicaecorum,a butyrate producer with probiotic potential,is intrinsically tolerant to stomach and small intestine conditions[J]. Anaerobe,2014,30:70.
[32] Meehan C J,Beiko R G. A phylogenomic view of ecological specialization in the Lachnospiraceae,a family of digestive tract-associated bacteria[J]. Genome Biol Evol,2014,6(3):703.
[33] Sun M,Wu W,Liu Z,et al. Microbiota metabolite short chain fatty acids,GPCR,and inflammatory bowel diseases[J]. J Gastroenterol,2017,52(1):1.
[34] Shang Q,Shan X,Cai C,et al. Dietary fucoidan modulates the gut microbiota in mice by increasing the abundance of Lactobacillus and Ruminococcaceae[J]. Food Funct,2016,7(7):3224.
[35] Park S,Kim D S,Kang S. Gastrodia elata Blume water extracts improve insulin resistance by decreasing body fat in diet-induced obese rats:vanillin and 4-hydroxybenzaldehyde are the bioactive candidates[J]. Eur J Nutr,2011,50(2):107.
[36] Yang H J,Kim M J,Kwon D Y,et al. Anti-diabetic activities of Gastrodia elata Blume water extracts are mediated mainly by potentiating glucose-stimulated insulin secretion and increasing beta-cell mass in non-obese type 2 diabetic animals[J]. Nutrients,2016,8(3):161.
[2] Matias M,Silvestre S,Falcao A,et al. Gastrodia elata and epilepsy:rationale and therapeutic potential[J]. Phytomedicine,2016,23(12):1511.
[3] Zhang J S,Zhou S F,Wang Q,et al. Gastrodin suppresses BACE1 expression under oxidative stress condition via inhibition of the PKR/e IF2alpha pathway in Alzheimer's disease[J]. Neuroscience,2016,325:1.
[4] Huang J Y,Yuan Y H,Yan J Q,et al. 20C,a bibenzyl compound isolated from Gastrodia elata,protects PC12 cells against rotenone-induced apoptosis via activation of the Nrf2/ARE/HO-1signaling pathway[J]. Acta Pharmacol Sin,2016,37(6):731.
[5] Duparc T,Plovier H,Marrachelli V G,et al. Hepatocyte My D88affects bile acids,gut microbiota and metabolome contributing to regulate glucose and lipid metabolism[J]. Gut, 2017, 66(4):620.
[6] Utzschneider K M,Kratz M,Damman C J,et al. Mechanisms linking the gut microbiome and glucose metabolism[J]. J Clin Endocrinol Metab,2016,101(4):1445.
[7]孙艺凡,张霞,王晓艳,等.长期服用人参提取物对大鼠肠道菌群结构的影响[J].中国中药杂志,2018,43(19):3927.
[8] Mayer E A,Knight R,Mazmanian S K,et al. Gut microbes and the brain:paradigm shift in neuroscience[J]. J Neurosci,2014,34(46):15490.
[9] Magoc T,Salzberg S L. FLASH:fast length adjustment of short reads to improve genome assemblies[J]. Bioinformatics,2011,27(21):2957.
[10] Edgar R C. Search and clustering orders of magnitude faster than BLAST[J]. Bioinformatics,2010,26(19):2460.
[11] Caporaso J G,Kuczynski J,Stombaugh J,et al. QIIME allows analysis of high-throughput community sequencing data[J]. Nat Methods,2010,7(5):335.
[12] Segata N,Izard J,Waldron L,et al. Metagenomic biomarker discovery and explanation[J]. Genome Biol,2011,12(6):R60.
[13] Langille M G,Zaneveld J,Caporaso J G,et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences[J]. Nat Biotechnol,2013,31(9):814.
[14] Han Y J,Je J H,Kim S H,et al. Gastrodia elata shows neuroprotective effects via activation of PI3K signaling against oxidative glutamate toxicity in HT22 cells[J]. Am J Chin Med,2014,42(4):1007.
[15] Chen W C,Lai Y S,Lin S H,et al. Anti-depressant effects of Gastrodia elata Blume and its compounds gastrodin and4-hydroxybenzyl alcohol,via the monoaminergic system and neuronal cytoskeletal remodeling[J]. J Ethnopharmacol,2016,182:190.
[16]刘娜,张振兴,马金刚,等.天麻素药代动力学和组织分布特征研究[J].药物分析杂志,2015,35(8):1369.
[17] Zhang W,Sheng Y X,Zhang J L. Determination and pharmacokinetics of gastrodin and p-hydroxybenzylalcohol after oral administration of Gastrodia elata Bl. extract in rats by high-performance liquid chromatography-electrospray ionization mass spectrometric method[J]. Phytomedicine,2008,15(10):844.
[18]杨飞,王信,马传江,等.天麻加工炮制、成分分析与体内代谢研究进展[J].中国中药杂志,2018,43(11):2207.
[19] Turnbaugh P J,Backhed F,Fulton L,et al. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome[J]. Cell Host Microbe, 2008, 3(4):213.
[20] Turnbaugh P J,Ley R E,Mahowald M A,et al. An obesity-associated gut microbiome with increased capacity for energy harvest[J]. Nature,2006,444(7122):1027.
[21] Xiao S,Fei N,Pang X,et al. A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome[J]. FEMS Microbiol Ecol, 2014, 87(2):357.
[22] Tomova A,Husarova V,Lakatosova S,et al. Gastrointestinal microbiota in children with autism in Slovakia[J]. Physiol Behav,2015,138:179.
[23] Kang D W,Admas J B,Gregory A C,et al. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms:an open-label study[J]. Microbiome,2017,5(1):10.
[24] Zhang-Sun W,Augsto L A,Zhao L,et al. Desulfovibrio desulfuricans isolates from the gut of a single individual:structural and biological lipid A characterization[J]. FEBS Lett,2015,589(1):165.
[25] Yin J,Liao S X,He Y,et al. Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with largeartery atherosclerotic stroke or transient ischemic attack[J]. J Am Heart Assoc,2015,4(11):e002699.
[26] Chiodin R J,Dowd S E,Chamberlin W M,et al. Microbial population differentials between mucosal and submucosal intestinal tissues in advanced crohn's disease of the ileum[J]. PLoS ONE,2015,10(7):e0134382.
[27] Chen Y J,Wu H,Wu S D,et al. Parasutterella,in association with irritable bowel syndrome and intestinal chronic inflammation[J]. J Gastroenterol Hepatol,2018,33(11):1844.
[28] Zhao L,Zhang Q,Ma W,et al. A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota[J]. Food Funct,2017,8(12):4644.
[29] Eeckhaut V,Machiels K,Perrier C,et al. Butyricicoccus pullicaecorum in inflammatory bowel disease[J]. Gut,2013,62(12):1745.
[30] Fujio-Vejar S,Vasquez Y,Morales P,et al. The gut microbiota of healthy chilean subjects reveals a high abundance of the phylum verrucomicrobia[J]. Front Microbiol,2017,8:1221.
[31] Geirnaer A,Steyaert A,Eeckhaut V,et al. Butyricicoccus pullicaecorum,a butyrate producer with probiotic potential,is intrinsically tolerant to stomach and small intestine conditions[J]. Anaerobe,2014,30:70.
[32] Meehan C J,Beiko R G. A phylogenomic view of ecological specialization in the Lachnospiraceae,a family of digestive tract-associated bacteria[J]. Genome Biol Evol,2014,6(3):703.
[33] Sun M,Wu W,Liu Z,et al. Microbiota metabolite short chain fatty acids,GPCR,and inflammatory bowel diseases[J]. J Gastroenterol,2017,52(1):1.
[34] Shang Q,Shan X,Cai C,et al. Dietary fucoidan modulates the gut microbiota in mice by increasing the abundance of Lactobacillus and Ruminococcaceae[J]. Food Funct,2016,7(7):3224.
[35] Park S,Kim D S,Kang S. Gastrodia elata Blume water extracts improve insulin resistance by decreasing body fat in diet-induced obese rats:vanillin and 4-hydroxybenzaldehyde are the bioactive candidates[J]. Eur J Nutr,2011,50(2):107.
[36] Yang H J,Kim M J,Kwon D Y,et al. Anti-diabetic activities of Gastrodia elata Blume water extracts are mediated mainly by potentiating glucose-stimulated insulin secretion and increasing beta-cell mass in non-obese type 2 diabetic animals[J]. Nutrients,2016,8(3):161.