pissn eissn J. Milk Sci. Biotechnol. 2019;37(1): REVIEW 발효유의혈중콜레스테롤조절기능과발효유기능성에대한장

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1 pissn eissn J. Milk Sci. Biotechnol. 2019;37(1): REVIEW 발효유의혈중콜레스테롤조절기능과발효유기능성에대한장내균총구성의영향 김유진 1 윤요한 1,2 이수민 1,2* 1 숙명여자대학교식품영양학과, 2 숙명여자대학교위해분석연구센터 Serum Cholesterol-lowering Effect of Fermented Milk and Effect of Intestinal Microflora Composition on Function of Fermented Milk Yujin Kim 1, Yohan Yoon 1,2, and Soomin Lee 1,2* 1 Dept. of Food and Nutrition, Sookmyung Women's University, Seoul, Korea 2 Risk Analysis Research Center, Sookmyung Women's University, Seoul, Korea Received: March 13, 2019 Revised: March 20, 2019 Accepted: March 21, 2019 *Corresponding author : Soomin Lee Risk Analysis Research Center, Sookmyung Women's University, Seoul, Korea Tel : Fax : slee0719@naver.com Copyright 2019 Korean Society of Milk Science and Biotechnology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( creativecommons.org/ licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ORCID Yujin Kim Yohan Yoon Soomin Lee Abstract Fermented milk has been developed with its functionalities, and its health-promoting ability has been spotlighted due to its relationship with diseases such as cancer, cardiovascular disease, and diabetes, and gut microbiota. As national burden of cardiovascular disease increases over time, there is a need to prevent hypercholesterolemia. To achieve that, gut microbiota, which is altered by host s diet and environment, plays important roles in lowering cholesterol in the blood. Moreover, fermented milk may be effective as a cholesterol-lowering agent by altering gut microbiota composition. Gut microbiota may alter not only functions of the fermented milk but also bio-accessibility of functional materials. These results suggested that gut microbiota composition influences the impact of fermented milk. Thus, we should understand how functional materials are degraded by gut microbiota and absorbed into the gut. Keywords fermented milk, yogurt, cholesterol, gut microbiota 서론 사람의장내균총 (Gut microbiota) 은체세포수의약 10 배에달하는수의미생물의군집을말하며, 장관속에존재한다 (Conlon and Bird, 2015). 장내균총은사람의건강에서중요한역할을하며, 최근몇년간장내균총의불균형이과민성장증후군 (Irritable Bowel Syndrome) 을포함한여러 질병과관련이있는것으로밝혀지고있다 (Manichanh et al., 2006; Clemente et al., 2012; Tremaroli and Bäckhed, 2012). 이에따라장내균총의균형을맞춰주며인체에유익한것으로 잘알려져있는발효유에대한중요성은지속적으로증가하고있다. 발효유는 원유또는유가공품을 유산균혹은효모로발효시킨것이거나, 이에식품또는식품첨가물을가한것 으로정의된다 ( 식품의 약품안전처, 2018). 발효유는프로바이오틱스를인체내에매개할수있는용이한식품급원으로 접근성이높아소비자들에게있어건강증진가치가큰식품이다. 콜레스테롤은체내의세포막을구성하고스테로이드호르몬의전구체이며, 담즙의원료로서생명유 지에필요한성분이다. 체내콜레스테롤의 80% 는간에서, 20% 는식이에의해구성되는데, 섭취한 콜레스테롤이나체내합성콜레스테롤이과다한경우, 고콜레스테롤혈증으로인한동맥경화, 심근경 J Milk Sci Biotechnol Vol. 37, No. 1 27

2 Kim et al. 색, 뇌졸중등의심뇌혈관질환위험이증가한다 (Choi et al., 2017). 고콜레스테롤혈증을포함한이상지질혈증은최근몇년간미국을포함한여러나라에서발생률이감소하고있으나 (Benjamin et al., 2017), 우리나라의경우오히려증가하고있다 (KCDC, 2015) 년기준으로, 우리나라사망자의사망원인중심혈관질환이 19% 에달하였으며, 10년간심장질환에대한사망률은약 1.4배증가하였다 (Ha et al., 2015). 또한, OECD 에따르면우리나라의인구 10만명당뇌혈관질환으로인한사망자수는 OECD 평균보다높은것으로보고된바있다 (OECD, 2015). 이와같은고콜레스테롤혈증으로인한심뇌혈관질환의발병은곧사회경제적손실로이어진다. 2016년국민건강보험공단조사에따르면, 순환기계질환진료비는 8조원으로조사되었으며, 이는암진료비 5조 5천억원보다높은수치로, 국가에사회경제적으로부담이가중되고있다 ( 질병관리본부, 2018). 따라서, 심뇌혈관질환에대한적극적인예방을위해생활습관및식이습관개선을도모해야하며, 손쉬운방법으로서높은기호성과더불어기능성을가지는발효유를적극활용할수있다. 하지만, 건강한성인개인마다고유의장내균총을지니므로 (Lloyd-Price et al., 2016), 각기다른장내균총에따라발효유의기능성및효능이다르게나타날수있다. 따라서, 장내균총구성에따른기능성물질효능의변화에대한고찰이필요하고, 발효유의기능성과발효유의혈중콜레스테롤조절기작, 장내균총에따른발효유의기능성및효능의변화에대하여살펴보고자한다. 본론 1. 발효유의기능성소비자의발효유섭취목적은보편적으로장기능과칼슘보충등건강증진에있다 ( 국립축산과학원, 2016). 2018년에꼽힌발효유의주요소비트렌드키워드는발효유의효능이다 ( 한국농수산식품유통공사, 2018). 이와같이극대화된프로바이오틱스등의발효유효능에관심이증가함에따라국내외에서발효유의기능성을강조한발효유제품시장이확대되고있는추세이다 ( 한국농수산식품유통공사, 2018). 이러한발효유의기능성은주요하게장내유익균의생장증진과이에따른유해균의생장제어, 즉, 장내균총의제어를통한장관건강과면역의개선, 유당불내증, 알러지반응의완화, 심혈관계질환개선효과, 항당뇨, 항균등으로알려져있다 (Adolfsson et al., 2004). 현재까지면역조절기능과관련한기작으로, 발효유내프로바이오틱스가장벽에기능을안정화하고장내 IgA(Immunoglobulin A) 의생성을자극하여낮아진면역력을증진시키며, 염증성사이토카인의분비를조절하는것으로알려져있다 (Rosenfeldt et al., 2004). 프로바이오틱스가지니는면역조절작용과더불어발효유가발효되면서생성되는스핑고지질 (sphingolipids), 포합리놀레산 (conjugated linoleic acid), 뷰티르산 (butyric acid) 과같은비영양소구성물질 (non-nutrient components) 도프로바이오틱스와함께암이나만성질환예방에중요한역할을한다 (Sanders et al., 2007). 2. 발효유를통한혈중콜레스테롤의조절발효유의심혈관계질환개선효과는근본적으로혈중콜레스테롤을조절함에있다. 젖산균 ( 혹은프로바이오틱스 ) 에의해혈중콜레스테롤이조절되는기작은크게 3가지로알려져있다. 젖산균이장내에정착하고증식함에따라콜레스테롤이젖산균에흡착하는기작 (Sadzikowski et al., 1977) 과, 젖산균이담즙산과흡착하여배설된후배설된담즙산을보충하기위해간에서혈중콜레스테롤을이용하여최종체내콜레스테롤의농도가감소하는기작이밝혀져있다 (Gilliland et al., 1985). 또한, 젖산균의답즙산염가수분해효소 (bile salt hydrolase) 는지질용해도가높은포합담즙산 (conjugated bile acid) 을탈포합 (deconjugation) 하여혈중으로흡수되는콜레스테롤의농도를낮추는기작이 28 J Milk Sci Biotechnol Vol. 37, No. 1

3 발효유의기능과발효유기능성에대한장내균총구성의영향 보고되었다 (Ooi and Liong, 2010). 이와같은기작을기반으로프로바이오틱스를사용한발효유를섭취했을때혈중콜레스테롤을감소시킬수있다 (Ataie-Jafari et al., 2009; Ishimwe et al., 2015). 발효유내젖산균외에도발효유젖산균의효소및대사생성물에의해서도조절이가능하다. 유제품이발효되면서생성되는뷰티르산 (butyrate) 이간세포에서콜레스테롤을합성하는효소인 HMG-CoA(HDL 3 hydroxy 3 methylglutaryl CoA) 환원효소의활성을감소시켜혈중콜레스테롤을조절한다 (Marcil et al., 2003). 또한특정한젖산균 (Lactobacillus acidophilus, L. bulgaricus, L. casei ATCC 393) 은세포내외에콜레스테롤환원효소를지녀콜레스테롤을코프로스타놀 (coprostanol) 로환원및전환한다는것이보고된바있다 (Lye et al., 2010). 발효유의젖산균및대사산물에의한콜레스테롤감소뿐만아니라, 발효유에의해변화한장내균총또한혈중콜레스테롤저하에기여할수있다. 이와관련하여랫트, 마우스, 돼지, 기니피그동물모델을통한연구에서장내균총을변화시켰을때체내에서지질대사가변화하여혈중콜레스테롤이저하됨을관찰한바있다 (Liong et al., 2007; Madsen et al., 2008; Lee et al., 2009; Pan et al., 2011). 3. 장내균총의구성에따른발효유의기능성및물질효능의변화장내균총은인종과생활습관, 유전적특징등개인마다지니는요인들에의해서로다르게나타나는데, 개인마다다른장내균총은식이성분들의체내이용효능을상이하게한다 (Conlon and Bird, 2015). 장내균총의구성과비율은위에서언급한요인중에서도식이가주요한요인이되며 (Conlon and Bird, 2015; Hall et al., 2017; Gaulke and Sharpton, 2018), 섭취하는거대영양소 (macronutrients) 및식이의차이에따라크게 3가지의장유형 (enterotype) 으로분류된다 (Arumugam et al., 2011). 장유형은주요하게장내균총을이루는속 (genus) 인 Bacteroides, Prevotella, Ruminococcus 의비율에따라분류된다. 고단백질및고지방식이를섭취했을때는 Bacteroides 유형으로, 탄수화물및고식이섬유섭취는 Prevotella 유형, 특정식이와의연관성을나타내지않는 Ruminococcus 유형으로분류된다 (Arumugam et al., 2011). 이렇게식이에의해달라진장내균총은혈중콜레스테롤의제어에영향을줄수있다. 장내균총은장내에서콜레스테롤의전환에관여할수있으며, 이에대한효율성은콜레스테롤을전환하는세균이풍부하게있는가에따라결정된다 (Gérard, 2014). 사람에서분리되고연구된콜레스테롤전환박테리아는현재까지 Bacteroides D8균주로알려졌으며, 랫트에서는 Eubacterum 속이콜레스테롤전환을일으키고, 그중에서도 E. coprostanoligenes ATCC 가새로운균주로서명명된바있다 (Freier et al., 1994). 장내균총구성의변화에따른기능성물질의장내흡수및효능변화에대한가능성도제시되었다. 그예시로장내균총의구성이각기다른개개인에서진세노사이드의장내흡수가달라져장내균총의구성에의해특정물질의효능이결정될수있다고연구된바있다 (Kim et al., 2013). 또한, 과일, 야채, 곡물에서발견되는기능성물질인폴리페놀 (polyphenol) 은암, 심혈관질환을예방한다고알려져각광받고있는데, 이는소장에서의흡수정도에따라체내에서효과를나타낸다. 어떠한폴리페놀은자연계에서많이발견되나, 고유구조에따라생체이용이불가능한것으로알려져있으며 (Bohn, 2008), 이는장내균총에의해구조적으로변형되고작은분자로분해되었을때비로소소장에서흡수된다 (Ozdal et al., 2016). 이렇듯이개개인마다상이한장내균총에의해일반적으로알려져있는기능성물질들의체내흡수효율이달라질수있다. 결론 현재유제품시장에서발효유는기본효능과더불어차별화된기능성을더하여, 침체되어있는우유 시장이재기할수있는새로운돌파구로서잠재력이크다. 현재까지초년기의환경과식이패턴이 J Milk Sci Biotechnol Vol. 37, No. 1 29

4 Kim et al. 성인기의장내미생물정착화에영향을줄수있다는것은정설이되고있다 (Hanson and Gluckman, 2011). 또한, 장내균총과각종질환의연관성이밝혀지고있어발효유섭취에따른장내균총의조절이질환의예방혹은완화를위해복용하는약물을대체할수있을것으로기대되고있다. 하지만, 발효유의기능성이나기능성물질자체의궁극적인효능발휘를위해서는장내균총에의한물질의분해및흡수기작에대한심도있는연구가진행되어야할것이다. References Adolfsson, O., Meydani, S. N. and Russell, R. M Yogurt and gut function. Am. J. Clin. Nutr. 80: Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J. Bruls, T., Batto, J-M., Bertalan, M., Borruel, N., Casellas, F., Fernandez, L., Gautier, L., Hansen, T., Hattori, M., Hayashi, T., Kleerebezem, M., Kurokawa, K., Leclerc, M., Levenez, F., Manichanh, C., Nielsen, H. B., Nielsen, T., Pons, N., Poulain, J., Qin, J., Sicheritz-Ponten, T., Tims, S., Torrents, D., Ugarte, E., Zoetendal, E. G., Wang, J., Guarner, F., Pedersen, O., de Vos, W. M., Brunak, S., Doré, J., MetaHIT Consortium, Weissenbach, J., Ehrlich S. D. and Bork, P Enterotypes of the human gut microbiome. Nature 473: Ataie-Jafari, A., Larijani, B., Majd, H. A. and Tahbaz, F Cholesterol-lowering effect of probiotic yogurt in comparison with ordinary yogurt in mildly to moderately hypercholesterolemic subjects. Ann. Nutr. Metab. 54: Benjamin, E. J., Blaha, M. J., Chiuve, S. E., Cushman, M., Das, S. R., Deo, R.,... and Jiménez, M. C Heart disease and stroke statistics-2017 update: A report from the American Heart Association. Circulation 135:e146-e603. Bohn, T Bioavailability of non-provitamin a carotenoids. Curr. Nutr. Food Sci. 4: Choi, Y., Lee, S., Kim, J. Y. and Lee, K. E Current guidelines on the management of dyslipidemia. Kor. J. Clin. Pharm. 27: Clemente, J. C., Ursell, L. K., Parfrey, L. W. and Knight, R The impact of the gut microbiota on human health: An integrative view. Cell. 148: Conlon, M. and Bird, A The impact of diet and lifestyle on gut microbiota and human health. Nutrients 7: Freier, T. A., Beitz, D. C., Li, L. and Hartman, P. A Characterization of Eubacterium coprostanoligene sp. nov., a cholesterol-reducing anaerobe. Int. J. Syst. Bacteriol. 44: Gaulke, C. A. and Sharpton, T. J The influence of ethnicity and geography on human gut microbiome composition. Nat. Med. 24:1495. Gérard, P Metabolism of cholesterol and bile acids by the gut microbiota. Pathogens. 3: Gilliland, S. E., Nelson, C. R. and Maxwell, C Assimilation of cholesterol by Lactobacillus acidophilus. Appl. Environ. Microbiol. 49: Ha, K. H., Kwon, H. S. and Kim, D. J Epidemiologic characteristics of dyslipi- 30 J Milk Sci Biotechnol Vol. 37, No. 1

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Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract