메뉴 건너뛰기




Volumn 26, Issue 1, 2010, Pages 5-11

Obesity and the human microbiome

Author keywords

Gut microbial ecology; Inflammation; Insulin resistance; Metagenomics; Microbiota; Obesity

Indexed keywords

BACTERIAL METABOLISM; ENDOCRINE CELL; HUMAN; INSULIN RESISTANCE; INTESTINE FLORA; METAGENOMICS; MICROBIAL DIVERSITY; MICROBIOME; NONHUMAN; OBESITY; REVIEW; WEIGHT REDUCTION;

EID: 74249119678     PISSN: 02671379     EISSN: None     Source Type: Journal    
DOI: 10.1097/MOG.0b013e328333d751     Document Type: Review
Times cited : (656)

References (54)
  • 3
    • 33845874101 scopus 로고    scopus 로고
    • An obesity-associated gut micro biome with increased capacity for energy harvest
    • Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444:1027-1031.
    • (2006) Nature , vol.444 , pp. 1027-1031
    • Turnbaugh, P.J.1    Ley, R.E.2    Mahowald, M.A.3
  • 4
    • 33845901507 scopus 로고    scopus 로고
    • Microbial ecology: Human gut microbes associated with obesity
    • Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444:1022-1023.
    • (2006) Nature , vol.444 , pp. 1022-1023
    • Ley, R.E.1    Turnbaugh, P.J.2    Klein, S.3    Gordon, J.I.4
  • 5
    • 58749112734 scopus 로고    scopus 로고
    • A core gut micro biome in obese and lean twins
    • Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature 2009; 457:480-484.
    • (2009) Nature , vol.457 , pp. 480-484
    • Turnbaugh, P.J.1    Hamady, M.2    Yatsunenko, T.3
  • 6
    • 73949137604 scopus 로고    scopus 로고
    • Microbiota and SCFA in lean and overweight healthy subjects
    • doi: 10.1038/oby.2009.167. [Epub ahead of print]
    • Schwiertz A, Taras D, Schafer K, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity 2009. doi: 10.1038/oby.2009.167. [Epub ahead of print]
    • (2009) Obesity
    • Schwiertz, A.1    Taras, D.2    Schafer, K.3
  • 7
    • 53849104768 scopus 로고    scopus 로고
    • Distinct composition of gut micro biota during pregnancy in overweight and normal-weight women
    • Collado MC, Isolauri E, Laitinen K, Salminen S. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr 2008; 88:894-899.
    • (2008) Am J Clin Nutr , vol.88 , pp. 894-899
    • Collado, M.C.1    Isolauri, E.2    Laitinen, K.3    Salminen, S.4
  • 9
    • 56549122798 scopus 로고    scopus 로고
    • Human colonic micro biota associated with diet, obesity and weight loss
    • Duncan SH, Lobley GE, Holtrop G, et al. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obesity 2008; 32:1720-1724.
    • (2008) Int J Obesity , vol.32 , pp. 1720-1724
    • Duncan, S.H.1    Lobley, G.E.2    Holtrop, G.3
  • 10
    • 40549088230 scopus 로고    scopus 로고
    • Early differences in fecal micro biota composition in children may predict overweight
    • Kalliomaki M, Collado C, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr 2008; 87:534-538.
    • (2008) Am J Clin Nutr , vol.87 , pp. 534-538
    • Kalliomaki, M.1    Collado, C.2    Salminen, S.3    Isolauri, E.4
  • 11
    • 70349502267 scopus 로고    scopus 로고
    • Interplay between weight loss and gut micro biota composition in overweight adolescents
    • doi: 10.1038/oby.2009.112. [Epub ahead of print]
    • Santacruz A, Marcos A, Warnberg J, et al. Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity 2009. doi: 10.1038/oby.2009.112. [Epub ahead of print]
    • (2009) Obesity
    • Santacruz, A.1    Marcos, A.2    Warnberg, J.3
  • 12
    • 67650445962 scopus 로고    scopus 로고
    • Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents
    • Nadal I, Santacruz A, Marcos A, et al. Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents. Int J Obesity 2009; 33:758-767.
    • (2009) Int J Obesity , vol.33 , pp. 758-767
    • Nadal, I.1    Santacruz, A.2    Marcos, A.3
  • 13
    • 43349107591 scopus 로고    scopus 로고
    • High prevalence of small intestinal bacterial overgrowth in patients with morbid obesity: A contributor to severe hepatic steatosis
    • Sabate J, Jouet P, Harnois F, et al. High prevalence of small intestinal bacterial overgrowth in patients with morbid obesity: a contributor to severe hepatic steatosis. Obesity Surg 2008; 18:371-377.
    • (2008) Obesity Surg , vol.18 , pp. 371-377
    • Sabate, J.1    Jouet, P.2    Harnois, F.3
  • 14
    • 60549086580 scopus 로고    scopus 로고
    • Human gut micro biota in obesity and after gastric bypass
    • Zhang H, DiBaise J, Zuccolo A, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A 2009; 106:2365-2370.
    • (2009) Proc Natl Acad Sci U S A , vol.106 , pp. 2365-2370
    • Zhang, H.1    Dibaise, J.2    Zuccolo, A.3
  • 15
    • 69949111703 scopus 로고    scopus 로고
    • The core gut micro biome, energy balance, and obesity
    • Turnbaugh P, Gordon J. The core gut microbiome, energy balance, and obesity. J Physiol 2009; 587(Pt 17):4153-4258.
    • (2009) J Physiol , vol.587 , Issue.PART 17 , pp. 4153-4258
    • Turnbaugh, P.1    Gordon, J.2
  • 16
    • 54249110955 scopus 로고    scopus 로고
    • Development of a real-time PCR method for Firmicutes and Bacteroidetes in faeces and its application to quantify intestinal population of obese and lean pigs
    • Guo X, Xia X, Tang R, et al. Development of a real-time PCR method for Firmicutes and Bacteroidetes in faeces and its application to quantify intestinal population of obese and lean pigs. Lett Appl Microbiol 2008; 47:367-373.
    • (2008) Lett Appl Microbiol , vol.47 , pp. 367-373
    • Guo, X.1    Xia, X.2    Tang, R.3
  • 17
    • 58149280426 scopus 로고    scopus 로고
    • Developmental changes of gut micro flora and enzyme activity in rat pups exposed to fat-rich diet
    • Mozes S, Bujnakova D, Sefcikova Z, Kmet V. Developmental changes of gut microflora and enzyme activity in rat pups exposed to fat-rich diet. Obesity 2008; 16:2610-2615.
    • (2008) Obesity , vol.16 , pp. 2610-2615
    • Mozes, S.1    Bujnakova, D.2    Sefcikova, Z.3    Kmet, V.4
  • 19
    • 41849127118 scopus 로고    scopus 로고
    • Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut micro biome
    • Turnbaugh P, Bäckhed F, Fulton L, Gordon J. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 2008; 3:213-223.
    • (2008) Cell Host Microbe , vol.3 , pp. 213-223
    • Turnbaugh, P.1    Bäckhed, F.2    Fulton, L.3    Gordon, J.4
  • 20
    • 66749118301 scopus 로고    scopus 로고
    • Top-down systems biology modeling of host metabotype micro biome associations in obese rodents
    • Waldram A, Holmes E, Wang Y, et al. Top-down systems biology modeling of host metabotype microbiome associations in obese rodents. J Proteome Res 2009; 8:2361-2375.
    • (2009) J Proteome Res , vol.8 , pp. 2361-2375
    • Waldram, A.1    Holmes, E.2    Wang, Y.3
  • 21
    • 33847233644 scopus 로고    scopus 로고
    • Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces
    • Duncan SH, Belenguer A, Holtrop G, et al. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol 2007; 73:1073-1078.
    • (2007) Appl Environ Microbiol , vol.73 , pp. 1073-1078
    • Duncan, S.H.1    Belenguer, A.2    Holtrop, G.3
  • 22
    • 70349233883 scopus 로고    scopus 로고
    • Towards the human intestinal micro biota phylogenetic core
    • Tap J, Mondot S, Levenez F, et al. Towards the human intestinal microbiota phylogenetic core. Environ Microbiol 2009; 11:2579-2584.
    • (2009) Environ Microbiol , vol.11 , pp. 2579-2584
    • Tap, J.1    Mondot, S.2    Levenez, F.3
  • 23
    • 67650473912 scopus 로고    scopus 로고
    • Regulation of myocardial ketone body metabolism by the gut micro biota during nutrient deprivation
    • Crawford P, Crowley J, Sambandam N, et al. Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation. Proc Natl Acad Sci U S A 2009; 27:11276-11281.
    • (2009) Proc Natl Acad Sci U S A , vol.27 , pp. 11276-11281
    • Crawford, P.1    Crowley, J.2    Sambandam, N.3
  • 25
    • 67649161262 scopus 로고    scopus 로고
    • Intestinal micro biota during infancy and its implications for obesity
    • Reinhardt C, Reigstad CS, Bäckhed F. Intestinal microbiota during infancy and its implications for obesity. J Pediatr Gastroenterol Nutr 2009; 48:249-256.
    • (2009) J Pediatr Gastroenterol Nutr , vol.48 , pp. 249-256
    • Reinhardt, C.1    Reigstad, C.S.2    Bäckhed, F.3
  • 26
    • 67650604595 scopus 로고    scopus 로고
    • The role of the gut micro biota in energy metabolism and metabolic disease
    • Cani PD, Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Design 2009; 15:1546-1558.
    • (2009) Curr Pharm Design , vol.15 , pp. 1546-1558
    • Cani, P.D.1    Delzenne, N.M.2
  • 27
  • 28
    • 8144226856 scopus 로고    scopus 로고
    • The gut micro biota as an environmental factor that regulates fat storage
    • Bäckhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 2004; 101: 15718-15723.
    • (2004) Proc Natl Acad Sci U S A , vol.101 , pp. 15718-15723
    • Bäckhed, F.1    Ding, H.2    Wang, T.3
  • 29
    • 32644454369 scopus 로고    scopus 로고
    • The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity
    • Mandard S, Zandbergen F, van Straten E, et al. The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity. J Biol Chem 2006; 281:934-944.
    • (2006) J Biol Chem , vol.281 , pp. 934-944
    • Mandard, S.1    Zandbergen, F.2    Van Straten, E.3
  • 30
    • 34047177395 scopus 로고    scopus 로고
    • Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL
    • Romeo S, Pennacchio L, Fu Y, et al. Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nat Genet 2007; 39:513-516.
    • (2007) Nat Genet , vol.39 , pp. 513-516
    • Romeo, S.1    Pennacchio, L.2    Fu, Y.3
  • 31
    • 84977826018 scopus 로고    scopus 로고
    • Muscle-derived angiopoietin-like protein 4 is induced by fatty acids via PPAR {delta} and is of metabolic relevance in humans
    • Staiger H, Haas C, Machann J, et al. Muscle-derived angiopoietin-like protein 4 is induced by fatty acids via PPAR {delta} and is of metabolic relevance in humans. Diabetes 2008; 53:579-589.
    • (2008) Diabetes , vol.53 , pp. 579-589
    • Staiger, H.1    Haas, C.2    MacHann, J.3
  • 32
    • 56749164791 scopus 로고    scopus 로고
    • Nutrient sensing and inflammation in metabolic diseases
    • Hotamisligil GS, Erbay E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 2008; 8:923-934.
    • (2008) Nat Rev Immunol , vol.8 , pp. 923-934
    • Hotamisligil, G.S.1    Erbay, E.2
  • 33
    • 0030061922 scopus 로고    scopus 로고
    • IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha-and obesity-induced insulin resistance
    • Hotamisligil G, Peraldi P, Budavari A, et al. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha-and obesity-induced insulin resistance. Science 1996; 271:665-670.
    • (1996) Science , vol.271 , pp. 665-670
    • Hotamisligil, G.1    Peraldi, P.2    Budavari, A.3
  • 34
    • 34347399563 scopus 로고    scopus 로고
    • Metabolic endotoxemia initiates obesity and insulin resistance
    • Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007; 56:1761-1772.
    • (2007) Diabetes , vol.56 , pp. 1761-1772
    • Cani, P.D.1    Amar, J.2    Iglesias, M.A.3
  • 35
    • 34547602916 scopus 로고    scopus 로고
    • Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance
    • Tsukumo D, Carvalho-Filho M, Carvalheira J, et al. Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 2007; 56:1886-1898.
    • (2007) Diabetes , vol.56 , pp. 1886-1898
    • Tsukumo, D.1    Carvalho-Filho, M.2    Carvalheira, J.3
  • 36
    • 33745584354 scopus 로고    scopus 로고
    • Acute-phase serum amyloid a: An inflammatory adipokine and potential link between obesity and its metabolic complications
    • Yang R-Z, Lee M-J, Hu H, et al. Acute-phase serum amyloid a: an inflammatory adipokine and potential link between obesity and its metabolic complications. PLoS Med 2006; 3:e287.
    • (2006) PLoS Med , vol.3
    • Yang, R.-Z.1    Lee, M.-J.2    Hu, H.3
  • 37
    • 50549093401 scopus 로고    scopus 로고
    • Acute-phase serum amyloid a as a marker of insulin resistance in mice
    • Scheja L, Heese B, Zitzer H, et al. Acute-phase serum amyloid a as a marker of insulin resistance in mice. Exp Diabetes Res 2008; 2008:230837.
    • (2008) Exp Diabetes Res , vol.2008 , pp. 230837
    • Scheja, L.1    Heese, B.2    Zitzer, H.3
  • 38
    • 67649225408 scopus 로고    scopus 로고
    • Regulation of serum amyloid A3 (SAA3) in mouse colonic epithelium and adipose tissue by the intestinal micro biota
    • Reigstad CS, Lunden GO, Felin J, Bäckhed F. Regulation of serum amyloid A3 (SAA3) in mouse colonic epithelium and adipose tissue by the intestinal microbiota. PLoS ONE 2009; 4:e5842.
    • (2009) PLoS ONE , vol.4
    • Reigstad, C.S.1    Lunden, G.O.2    Felin, J.3    Bäckhed, F.4
  • 39
    • 43549107065 scopus 로고    scopus 로고
    • Energy intake is associated with endotoxemia in apparently healthy men
    • Amar J, Burcelin R, Ruidavets JB, et al. Energy intake is associated with endotoxemia in apparently healthy men. Am J Clin Nutr 2008; 87:1219-1223.
    • (2008) Am J Clin Nutr , vol.87 , pp. 1219-1223
    • Amar, J.1    Burcelin, R.2    Ruidavets, J.B.3
  • 40
    • 63449098729 scopus 로고    scopus 로고
    • Chylomicrons promote intestinal absorption of lipopolysaccharides
    • Ghoshal S, Witta J, Zhong J, et al. Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res 2009; 50:90-97.
    • (2009) J Lipid Res , vol.50 , pp. 90-97
    • Ghoshal, S.1    Witta, J.2    Zhong, J.3
  • 41
    • 48249125862 scopus 로고    scopus 로고
    • Changes in gut micro biota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice
    • Cani P, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008; 57:1470-1481.
    • (2008) Diabetes , vol.57 , pp. 1470-1481
    • Cani, P.1    Bibiloni, R.2    Knauf, C.3
  • 42
    • 53249101515 scopus 로고    scopus 로고
    • Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells
    • Ma X, Hua J, Li Z. Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. J Hepatol 2008; 49:821-830.
    • (2008) J Hepatol , vol.49 , pp. 821-830
    • Ma, X.1    Hua, J.2    Li, Z.3
  • 43
    • 34848912627 scopus 로고    scopus 로고
    • Selective increases of bifidobacteria in gut micro flora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia
    • Cani P, Neyrinck A, Fava F, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 2007; 50:2374-2383.
    • (2007) Diabetologia , vol.50 , pp. 2374-2383
    • Cani, P.1    Neyrinck, A.2    Fava, F.3
  • 44
    • 65249099918 scopus 로고    scopus 로고
    • Changes in gut micro biota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability
    • Cani PD, Possemiers S, Van de Wiele T, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009; 58: 1091-1103.
    • (2009) Gut , vol.58 , pp. 1091-1103
    • Cani, P.D.1    Possemiers, S.2    Van De Wiele, T.3
  • 45
    • 33947182436 scopus 로고    scopus 로고
    • Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes
    • Creely S, McTernan P, Kusminski C. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab 2007; 292:E740.
    • (2007) Am J Physiol Endocrinol Metab , vol.292
    • Creely, S.1    McTernan, P.2    Kusminski, C.3
  • 46
    • 0033020969 scopus 로고    scopus 로고
    • Glucagon-like peptide 2
    • Drucker D. Glucagon-like peptide 2. Trends Endocrinol Metab 1999; 10:153-156.
    • (1999) Trends Endocrinol Metab , vol.10 , pp. 153-156
    • Drucker, D.1
  • 47
    • 0028109959 scopus 로고
    • Micro flora modulates endocrine cells in the gastrointestinal mucosa of the rat
    • Uribe A, Alam M, Johansson O, et al. Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat. Gastroenterology 1994; 107:1259-1269.
    • (1994) Gastroenterology , vol.107 , pp. 1259-1269
    • Uribe, A.1    Alam, M.2    Johansson, O.3
  • 48
    • 33748468927 scopus 로고    scopus 로고
    • Distinct signals from the micro biota promote different aspects of zebra fish gut differentiation
    • Bates J, Mittge E, Kuhlman J, et al. Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev Biol 2006; 297:374-386.
    • (2006) Dev Biol , vol.297 , pp. 374-386
    • Bates, J.1    Mittge, E.2    Kuhlman, J.3
  • 49
    • 34547965812 scopus 로고    scopus 로고
    • Dietary non digestible carbohydrates promote L-cell differentiation in the proximal colon of rats
    • Cani PD, Hoste S, Guiot Y, Delzenne NM. Dietary nondigestible carbohydrates promote L-cell differentiation in the proximal colon of rats. Br J Nutr 2007; 98:32-37.
    • (2007) Br J Nutr , vol.98 , pp. 32-37
    • Cani, P.D.1    Hoste, S.2    Guiot, Y.3    Delzenne, N.M.4
  • 50
    • 55949091259 scopus 로고    scopus 로고
    • Effects of the gut micro biota on host adiposity are modulated by the short-chain fatty-acid binding G protein coupled receptor, Gpr41
    • Samuel B, Shaito A, Motoike T, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G proteincoupled receptor, Gpr41. Proc Natl Acad Sci U S A 2008; 105:16767-16772.
    • (2008) Proc Natl Acad Sci U S A , vol.105 , pp. 16767-16772
    • Samuel, B.1    Shaito, A.2    Motoike, T.3
  • 51
    • 35649021752 scopus 로고    scopus 로고
    • Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass
    • le Roux C, Welbourn R, Werling M, et al. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg 2007; 246:780-785.
    • (2007) Ann Surg , vol.246 , pp. 780-785
    • Le Roux, C.1    Welbourn, R.2    Werling, M.3
  • 52
    • 67650417904 scopus 로고    scopus 로고
    • Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass
    • Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obesity 2009; 33:786-795.
    • (2009) Int J Obesity , vol.33 , pp. 786-795
    • Korner, J.1    Inabnet, W.2    Febres, G.3
  • 53
    • 34347230184 scopus 로고    scopus 로고
    • Microbial flora of the stomach after gastric bypass for morbid obesity
    • Ishida R, Faintuch J, Paula A, et al. Microbial flora of the stomach after gastric bypass for morbid obesity. Obesity Surg 2007; 17:756-762.
    • (2007) Obesity Surg , vol.17 , pp. 756-762
    • Ishida, R.1    Faintuch, J.2    Paula, A.3
  • 54
    • 67349117656 scopus 로고    scopus 로고
    • Probiotics improve outcomes after Roux-en-Y gastric bypass surgery: A prospective randomized trial
    • Woodard G, Encarnacion B, Downey J, et al. Probiotics improve outcomes after Roux-en-Y gastric bypass surgery: a prospective randomized trial. J Gastrointest Surg 2009; 13:1198-1204.
    • (2009) J Gastrointest Surg , vol.13 , pp. 1198-1204
    • Woodard, G.1    Encarnacion, B.2    Downey, J.3


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.