Changes inthe diet affect epigenetics via the microbiota

飲食變化通過微生物群影響表觀遺傳學

翻譯趙綺華

國家註冊營養師RD4300016

Posted: Wednesday, February 08, 2017

You are whatyou eat, the old saying goes, but why is that so? Researchers have known forsome time that diet affects the balance of microbes in our bodies, but how thattranslates into an effect on the host has not been understood. Now, research inmice is showing that microbes communicate with their hosts by sending outmetabolites that act on histones - thus influencing gene transcription not onlyin the colon but also in tissues in other parts of the body. The findings arepublished in Molecular Cell. "This is the first of what we hope is a long,fruitful set of studies to understand the connection between the microbiome inthe gut and its influence on host health," says John Denu, a professor ofbiomolecular chemistry at the University of Wisconsin, Madison, and one of thestudy"s senior authors. "We wanted to look at whether the gut microbiotaaffect epigenetic programming in a variety of different tissues in thehost."

老話說，你長啥樣都是你自己吃出來的，為什麼呢？研究揭示膳食可以影響我們體內的微生物平衡，然而它們如何進一步影響我們宿主，還不得而知。老鼠動物試驗表明，微生物通過在組蛋白上作用的代謝產物來與宿主交流，從而影響基因的轉錄，不僅在結腸中，而且在身體其他部位的組織中也有影響。研究結果發表在《分子細胞》上。「第一次，我們期望一個長期的富有成效的研究，以了解腸道微生物之間的聯繫及其對宿主健康的影響，」JohnDenu說，John Denu是威斯康辛大學麥迪遜生物分子化學教授，也是該研究的資深作者之一，「我們想看看腸道菌群是否會影響宿主體內各種不同組織的表觀遺傳。」

These tissueswere in the proximal colon, the liver, and fat tissue. In the study, theresearchers first compared germ-free mice with those that have active gutmicrobes and discovered that gut microbiota alter the host"s epigenome inseveral tissues. Next, they compared mice that were fed a normal chow diet tomice fed a Western-type diet - one that was low in complex carbohydrates andfiber and high in fat and simple sugars. Consistent with previous studies fromother researchers, they found that the gut microbiota of mice fed the normalchow diet differed from those fed the Western-type diet. "When the hostconsumes a diet that"s rich in complex plant polysaccharides (such as fiber),there"s more food available for microbes in the gut, because unlike simplesugars, our human cells cannot use them," explains Federico Rey, anassistant professor of bacteriology at UW-Madison and the study"s other seniorauthor.

這些組織位於近端結腸、肝臟和脂肪組織。在這項研究中，研究人員首先將無菌老鼠與具有活性腸道微生物的老鼠進行比較，並發現腸道菌群改變了宿主在幾個組織中的表觀基因組。接著，他們將餵食正常膳食的老鼠與餵食西式膳食的老鼠進行比較，西式膳食低複合碳水化合物低纖維，高脂肪和簡單糖。與之前其他研究人員的研究結果一致，他們發現餵食正常膳食的老鼠腸道微生物群有別於西式膳食的老鼠。「當宿主食用富含複雜植物多糖（如纖維）的飲食時，腸道內的微生物可利用的食物更多，因為複雜植物多糖與單糖不同，我們人類的細胞不能使用它們。」細菌學助理教授Federico Rey解釋說，Federico Rey來自威斯康星大學麥迪遜分校，也是該研究的資深作者。

Furthermore,they found that mice given a Western diet didn"t produce certain metabolites atthe same levels as mice who ate the healthier diet. "We thought that thosemetabolites - the short-chain fatty acids acetate, propionate, and butyrate,which are mostly produced by microbial fermentation of fiber - may be importantfor driving some of the epigenetic effects that we observed in mousetissues," Denu says. The next step was to connect changes in metaboliteproduction to epigenetic changes. When they looked at tissues in the mice, theyfound differences in global histone acetylation and methylation based on whichdiet the mice consumed. "Our findings suggest a fairly profound effect onthe host at the level of chromatin alteration," Denu explains. "Thismechanism affects host health through differential gene expression." Toconfirm that the metabolites were driving the epigenetic changes, theinvestigators then exposed germ-free mice to the three short-chain fatty acidsvia their drinking water to determine if these substances alone were enough toelicit the epigenetic changes. After looking at the mice"s tissues, they foundthat the epigenetic signatures in the mice with the supplemented water mimickedthe mice that were colonized by the microbes that thrive on the healthydiet.

此外，他們發現，給予西式膳食的老鼠不會產生與吃正常膳食的老鼠相同水平的某些代謝物。「我們認為那些代謝物——短鏈脂肪酸乙酸，丙酸和丁酸，主要由纖維的微生物發酵產生——對於驅動我們在老鼠組織中觀察到的一些表觀遺傳效應可能是重要的，」Denu說。下一步是將代謝產物的變化與表觀遺傳變化聯繫起來。當他們觀察老鼠的組織時，他們發現全球組蛋白乙醯化和甲基化的差異基於老鼠不同的膳食模式。「我們的發現表明在染色質改變水平上對宿主有相當深遠的影響，」Denu解釋說，「這種機制通過差異基因表達影響宿主健康。」為了確認確實是代謝物驅動了表觀遺傳變化，研究人員通過飲用水將無菌老鼠暴露於三種短鏈脂肪酸，以確定單獨這些物質是否足以引起表觀遺傳變化。在觀察老鼠的組織後，他們發現補充了水的老鼠表觀遺傳特徵模仿了那些在健康飲食中茁壯成長的微生物定殖的老鼠。

Additionalwork needs to be done to translate these findings from mice into humans."Obviously that"s a complex task," Denu says. "But we know thathuman microbial communities also generate these short-chain fatty acids, andthat you find them in the plasma in humans, so we speculate the same things aregoing on." Rey adds that butyrate-producing bacteria tend to occur atlower levels in people with diabetes and cardiovascular disease, and butyrateis also thought to have anti-inflammatory effects in the intestine. But theinvestigators don"t advocate supplementing the diet with short-chain fattyacids as a way around eating healthy. "Fruits and vegetables are a lotmore than complex polysaccharides," Rey says. "They have many othercomponents, including polyphenols, that are also metabolized in the gut and canpotentially affect chromatin in the host in ways that we don"t yet understand.Short-chain fatty acids are the tip of the iceberg, but they"re not the wholestory." This research was funded by the National Institutes of Health.

Kimberly A. Krautkramer, Julia H.Kreznar, Kymberleigh A. Romano, Eugenio I. Vivas, Gregory A. Barrett-Wilt, MaryE. Rabaglia, Mark P. Keller, Alan D. Attie, Federico E. Rey, John M. Denu,Diet-Microbiota Interactions Mediate Global Epigenetic Programming in MultipleHost Tissues, Molecular Cell, Available online 23 November 2016,

推鼠及人尚需時日，「顯然這是一項複雜的任務，」Denu說，「但我們已知人類微生物群落也會產生這些短鏈脂肪酸，並且可以在人體血漿中發現它們，所以我們推測同樣的事情正在發生。」

Rey補充說，產生丁酸的細菌往往在糖尿病和心血管疾病患者中低水平存在，丁酸鹽也被認為在腸道中具有抗炎作用。但研究人員並不主張用短鏈脂肪酸補充劑來實現健康膳食，「水果和蔬菜遠不僅僅是複雜的多糖，」Rey認為。「蔬果類還含有許多其他複合物，包括多酚類物質，它們也在腸道中代謝，並且可能會影響宿主的染色質，儘管機制未明。短鏈脂肪酸只是冰山一角，但它們遠不是故事的全部。」這項研究由美國國立衛生研究院資助。

Links :http://www.medicalnewstoday.com/releases/314344.php

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