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zoom RSS 腸内細菌が体重を左右する

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 人の腸内には10〜100兆の微生物、主に細菌が住んでいる。食物から何カロリーを取り出すか、脂肪にするか燃やすかといったことに、他の臓器と同様に影響を及ぼしている。
 マウスの腸内細菌と体重と代謝の間に重要な関連があるとわかった。人でも同様な関連があるようだ。
 我々が食べた食物から最大のカロリーを引き出してくれる細菌は狩猟採集生活を送っていた我々の祖先の時代には有益であったが、米国式のファーストフード食を食べる現代人には有益とはいえない。肥満や糖尿病の原因の一つとなっている可能性がある。
 体内を細菌で満たすことで病気を防ぐという方法をとってきたが、衛生状態の改善で状況も変わってきた。
 人が消化できないでんぷんなどを分解したり、ビタミンを生成したりして、腸内細菌なしではより病気にかかりやすくなるだろう。
 赤ん坊は細菌なしで生まれるが、出産途中とその後、母親など周囲から細菌を収集する。腸内細菌群は家族から引き継がれる。環境や食事からも細菌を取り入れるのでそれぞれ個人ごとに腸内細菌群は異なる。
 ネイチャー誌4月号の研究では、日本人の中には、すしに使われる海草の海苔の化合物を消化できる細菌を持っている人がいる。3月号には、人は少なくとも160種の腸内細菌を持っており、多くはbacteroidetesとfirmicutesの2種の中に含まれ、これらは土壌や水でも見つかる。病気を起こす菌もいくつかあるが多くは有益である。firmicutes類は特に食物の消化に役立っていて、多くのカロリーを引き出してくれる。
 2005年、ワシントン大のLey らは、肥満研究のためにマウスの腸内細菌を調べた。正常、やせ、レプチン遺伝子変異を持つ肥満マウスの3グループを比較した。主要な腸内細菌はヒト同様にbacteroidetesとfirmicutesの2種であったが、やせと肥満のマウスでは違いがあり、肥満マウスにはfirmicutesが多かった。また、腸内細菌を持たない無菌マウスではたくさん食べても太らない。肥満マウスの腸内細菌を無菌マウスに移すと体重増加が見られた。
 2006年のNature で報告されたLeyらの研究では、肥満の人で1年間のダイエットを行い、前後で腸内細菌を調査したところ、健常者に比べてfirmicutesの割合が多かったがダイエットの継続につれてbacteroidetesの割合が増加した。
 3月のScienceに発表されたGewirtz らの研究では、細菌が炎症を起こして食欲と体重を減らすという。さらにその炎症がインシュリンの体への感受性を変えたという。
 今月、日本の雪印乳業の研究者は、12週間体に良い細菌乳飲料を飲んだ人々が体重を減らしたことをEuropean Journal of Clinical Nutritionに報告した。BMIが1.5%、体重が1.4%減少した。
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腸内細菌叢は「第二の遺伝子」
http://kurie.at.webry.info/201003/article_9.html
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Gut bacteria may affect your weight
Don't go searching for a bacteria shake just yet ― scientists are still investigating which bacteria do what in humans.
By Amber Dance, Special to the Los Angeles Times
June 21, 2010
http://www.latimes.com/news/health/la-he-in-the-works-20100621,0,1401671,full.story

画像Between 10 trillion and 100 trillion microbes, mainly bacteria, dwell in a person's colon and small intestine. (Alex Nabaum / For The Times)

Something in your gut could be making you fat ― and it isn't just last night's pizza.

The vast, diverse community of microbes inhabiting the intestines, scientists are finding, can influence metabolism and weight.

Between 10 trillion and 100 trillion microbes, mainly bacteria, dwell in a person's colon and small intestine. They function together almost like another of the body's organs, influencing, among other things, how many calories we extract from our food and whether we make or burn fat. Researchers have discovered significant links between gut bacteria and weight and metabolism in mice ― and are starting to find similar associations in people.

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The story in humans is far from certain, though, and scientists say it's too soon to concoct microbe-filled "stay-slim" beverages ― a fact that has not prevented some companies from promoting their bacteria-laden products as helpful for weight loss.

Bacteria that draw the maximum calories from our food would have been useful to our hunter-gatherer ancestors but are less beneficial for modern people eating an American fast-food diet. In addition to our ready access to high-calorie eats, the bacteria we carry around have changed, says Andrew Gewirtz, an immunologist at Emory University in Atlanta, through antibiotic use, improved hygiene and cleanliness in the food supply.

This, he believes, could be one environmental cause for obesity and related conditions such as diabetes.

On the whole, our gut bacteria are beneficial, says Ruth Ley, a microbial ecologist at Cornell University in Ithaca, N.Y. They prevent disease-causing bacteria from taking hold in our body simply by filling up all the available space. And they help us digest foods, such as some starches, that we cannot break down ourselves, producing vitamins and energy sources we can use.

"You might just generally be sicklier without them," Ley says.

Babies are born bacteria-free but start to pick up bacteria during and after birth. Infants mostly collect bacteria from their mothers and others around them; in a sense, the gut community is inherited from family members. If the gut-obesity theory proved correct, that would suggest obesity risk could be passed along with them.

"If a person has changes in their gut bacteria ― and that could be due to anything, to diet, to antibiotic use ― if that person has kids, then they can transfer those gut bacteria and maybe transfer the problem," Gewirtz says.

Because people pick up different bacteria from their environments, people have different gut communities. For example, in a study published in the journal Nature in April, scientists reported that some Japanese people could digest compounds in nori, the seaweed in sushi, because they hosted the right bacteria for the job.

Every person carries at least 160 different kinds of gut bacteria, scientists estimated in another Nature study published in March. Most fall into two divisions, or phyla: the bacteroidetes and the firmicutes. Both of these groups are found in soil and water as well as in animals. Some cause disease, but many in the intestine are beneficial. The firmicutes, in particular, are good at digesting our food. The more firmicutes in a person's intestines, the more calories they can collect from a meal.

Obesity studies

This is where the obesity link comes in.

In 2005, Ley and colleagues at the Washington University School of Medicine in St. Louis, where she worked at the time, studied the gut bacteria found in mice, hoping to use them as a model to study obesity. They compared normal, lean mice with ones that were genetically obese because they had a mutation in the hormone leptin, which normally controls appetite and metabolism.

As in people, the main intestinal inhabitants of mice were bacteroidetes and firmicutes. But the researchers discovered that obese and lean mice had different proportions of each. In particular, fat mice tended to have more firmicutes, and fewer bacteroidetes, in their guts than lean mice.

In another study, Ley and colleagues worked with sterile mice that have no gut bacteria. These mice eat a lot, but don't get fat, presumably because they don't have the bacteria to extract the full complement of calories from their food. But when the scientists transferred the bacteria from fat mice to bacteria-free mice, the recipient mice gained weight. This result, reported in a 2006 Nature paper, directly suggests there's something about the bacterial community in the obese mice that contributes to weight gain.

What about human beings? Ley and co-workers examined the proportion of firmicutes and bacteroidetes in 12 people, in a study they also reported in Nature in 2006. They examined bacteria samples from obese people as they followed a yearlong diet program. Before the diet, the subjects had more firmicutes and fewer bacteroidetes than healthy-weight people. As the year progressed and the dieting continued, the bacteroidetes numbers went up, and the firmicutes numbers went down.

In addition to squeezing every last available calorie out of the food we eat, bacteria can also influence metabolism by signaling the body to store fat or burn less of it, and slow down food moving through the intestine so there is more time to collect calories.

The exact nature of the bacterial signals that influence metabolism is unclear, but in a March article published in the journal Science, Gewirtz and his colleagues reported that bacteria can cause inflammation that alters appetite and weight.

Normally, the immune system and gut bacteria maintain a kind of peace, Gewirtz says. But the mutant mice in this experiment were not normal: They lacked a protein needed to keep bacteria in the intestine where they belong, and out of the bloodstream. In these mice, gut bacteria leak out of the intestines and cause inflammation as the immune system responds to the intruders.

That inflammation, the scientists found, altered the body's sensitivity to insulin, a hormone that normally suppresses appetite and regulates blood sugar and fat storage. With the insulin system out of whack, the brain doesn't receive the crucial "I'm full! Put the fork down!" signal it needs to stop us chowing down.

This, in turn, led to a sort of "pre-diabetes" condition in the mice ― and by the time they were 20 weeks old, they weighed approximately 5 grams more than normal animals.

Gewirtz's team took the bacteria from the fattened mice and transplanted them into sterile, nonmutant mice. These mice then gained weight. Again, it seemed like just having the wrong bacteria can pack on the pounds.

Scientists have plenty of data that gut bacteria affect weight in mice, but their understanding of the effects in humans remains hazy. For example, not all human studies have shown that firmicutes go hand-in-hand with obesity in people, cautions Margaret Zupancic, a microbial genomicist at the University of Maryland School of Medicine in Baltimore.

In part, that is because it's much more difficult to study people in a carefully controlled way. People, after all, are out and about in the world and have a variety of food and exercise regimes, unlike genetically similar mice living in identical cages eating identical mouse chow.

Another fact hampering scientific study is that intestinal bacteria are difficult to grow in a laboratory setting. Thus, scientists must study the entire community from stool samples and try their best to figure out from those which bacteria serve specific functions.

To get a better handle on the human situation, Zupancic and others are now working with people in a variety of settings, collecting stool samples to further analyze the human gut community and how it interacts with our genetics and lifestyles.

If certain bacterial communities do cause obesity in people, replacing the bad bacteria with the good ones seems like a possible route to weight loss. The idea is not wholly unprecedented. Doctors occasionally treat debilitating diarrhea with a transplant of bacteria from healthy stool, for example. And there is certainly evidence that products called probiotics (see the sidebar) may improve health via a spoonful or swig of bacteria-laden foods. Even simply changing your diet might sway the bacterial community in a different direction, Ley says.

Next steps

Gewirtz says that someday it might be possible to swap obesity-linked bacteria for skinny-jean microbes. But scientists caution that a nice bacterial cocktail is not the next big weight-loss drink.

For one thing, they don't yet know what bacteria to use if they were to try and concoct such a drink. It is difficult to sort out the relationships between all the factors that lead to obesity, including diet, exercise, genetics ― and now, possibly, bacterial inhabitants.

And then, for a bacterial-replacement therapy to really work, doctors would first need a way to get rid of less desirable bacteria already in residence in someone's gastrointestinal tract. The right combination of antibiotics might do the job, Gewirtz says, but there are no well-defined methods for creating such a treatment.

Some companies, meanwhile, already are claiming that the right probiotics can slim you down. This month, researchers from the Japanese company Snow Brand Milk Products reported that people who drank a probiotic milk drink for 12 weeks lost weight. For their study, published in the European Journal of Clinical Nutrition, they offered the probiotic drink or a bacteria-free concoction to 87 people. The subjects were slightly heavy, with an average BMI (body mass index) of 24.2. (A BMI of 25 and above is considered to be overweight.)

Over the course of the study, people drinking the probiotic lost an average of 1.5% of their BMI and, on average, 1.4% of their body weight.

That's about 2 pounds for a 150-pound person.

health@latimes.com

Copyright (c) 2010, The Los Angeles Times

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