主题：【原创】健身成果咋样，懒汉们，该行动了。 -- 关中农民

肠道菌群。我的一个合作者发现有的口腔菌群竟然跟直肠癌有关联，我们正计划写基金呢，结果这大姐被耶鲁医学院挖走了。

我们医学院出身的，觉得活人不过比死人多口气而已，所以很多时候直肠子。

呵呵，你可以告诉她你跟医药同行了解过这类研究。不是拍脑袋想当然。

Published Online June 6 2012

Science 8 June 2012:

Vol. 336 no. 6086 pp. 1248-1250

DOI: 10.1126/science.336.6086.1248

News

News

My Microbiome and Me

Mara Hvistendahl

Zhao Liping combines traditional Chinese medicine and studies of gut microbes to understand and fight obesity.

Introduction

Perspectives

ScienceIs It Time for a Metagenomic Basis of Therapeutics?

ScienceHonor Thy Gut Symbionts Redux

Science Translational MedicineThe Human Gut Microbiota and Undernutrition

Paired Reviews

ScienceThe Application of Ecological Theory Toward an Understanding of the Human Microbiome

Science Translational MedicineMicrobiota-Targeted Therapies: Taking Advantage of Ecology

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ScienceHost-Gut Microbiota Metabolic Interactions

Science Translational MedicineTherapeutic Modulation of Microbiota-Host Metabolic Interactions

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ScienceInteractions Between the Microbiota and the Immune System

Science Translational MedicineMicrobiota, Disease and Back Again to Health: A Metastable Journey

Full Index for this Special Section

SHANGHAI, CHINA—In some ways it's a familiar story. In 1987, Zhao Liping married Ji Liuying, a college classmate. Within 2 years, they had a daughter and Zhao finished his Ph.D. Under new pressure and eating richly—Ji is a good cook—the microbiologist put on weight. By 1990, when he started an environmental microbiology lab at Shanxi Academy of Agricultural Sciences in Taiyuan, China, Zhao had grown from 60 to 80 kilograms. Later, on a postdoctoral fellowship at Cornell University, he put on another 10 kilograms. By the time he returned to China in 1995, his waist measured a corpulent 110 centimeters and his health was poor.

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The science of shrinking.

Microbiologist Zhao Liping, shown here before and after a change in diet, thinks he lost 20 kilograms by regulating his gut microbiota.

CREDITS: COURTESY OF ZHAO LIPING (2)

But in 2004, he read a paper that eventually changed the shape of his career—and his body. Jeffrey I. Gordon, a microbiologist at Washington University School of Medicine in St. Louis, Missouri, and colleagues showed a link between obesity and gut microbiota in mice (Science, 29 May 2009, p. 1136). Zhao was curious whether that link extended to himself and decided to find out. In 2006, he adopted a regimen involving Chinese yam and bitter melon—fermented prebiotic foods that are believed to change the growth of bacteria in the digestive system—and monitored not just his weight loss but also the microbes in his gut. When he combined these prebiotics with a diet based on whole grains, he lost 20 kilograms in 2 years. His blood pressure, heart rate, and cholesterol level came down. Faecalibacterium prausnitzii—a bacterium with anti-inflammatory properties—flourished, increasing from an undetectable percentage to 14.5% of his total gut bacteria. The changes persuaded him to focus on the microbiome's role in his transformation. He started with mice but has since expanded his research to humans.

Zhao—now a slim, soft-spoken 49-year-old with flat-top hair and a square jaw—has become an unlikely spokesperson for a burgeoning field. In 2010, he presented his weight-loss story at the Human Microbiome Project meeting in St. Louis, Missouri, at the invitation of George Weinstock of Washington University in St. Louis. Gordon's research had set off a flurry of new studies, but Weinstock says scientists had reached something of an impasse. The “field had been standardized to some extent by the early researchers following the same path,” Weinstock says, and Zhao's willingness to dive in and experiment on himself “brought a breath of fresh air.” Even more refreshing was that Zhao presented his findings in a “detached, agnostic, scientific way,” Weinstock adds. “He was not religious about it at all.”

Now associate director of Shanghai Jiao Tong University's Shanghai Center for Systems Biomedicine, Zhao oversees several clinical studies that look at the role of the microbiome in diabetes, obesity, and liver function. But his work remains grounded in his personal story—which friends say reflects a willingness to explore uncharted territory through raw trial and error. “As a scientist,” he says, “you should work on questions for which there is very little evidence but that you believe are important.”

Uncertainty about cause and effect is what plagues the field right now. It is difficult to prove, for example, that F. prausnitzii facilitated Zhao's slimming and didn't just show up once his gut was healthy. “The list of the diseases that the microbiome may play a role in is just growing and growing,” says Lita Proctor, director of the U.S. National Institutes of Health's Human Microbiome Project in Bethesda, Maryland. “But the problem is that we're only able to look at associations of the microbiome with disease and aren't yet able to conduct cause-and-effect studies. What we're witnessing is a very young field trying to figure out ‘Okay, what's the right way to approach [these] data?’”

For Zhao, the way involves transferring his weight-loss program to hundreds of human subjects and drawing on animal studies to decide what metabolic parameters to monitor in people. While his ultimate goal is to establish a molecular pathway connecting the microbiota to obesity, his e-mail signature reads: “EAT RIGHT, KEEP FIT, LIVE LONG, DIE QUICK.”

Faith in traditional medicine

Zhao grew up in a small farming town in Shanxi Province. Like most Chinese born on the eve of the Cultural Revolution, he and his two younger brothers had a simple upbringing. His father was a high school teacher and his mother worked in a textile factory. Both of his parents were firm believers in traditional remedies. Zhao remembers watching his father try to fight a hepatitis B infection by drinking a pungent, murky herbal concoction twice a day.

A good student, Zhao earned a Ph.D. in molecular plant pathology from Nanjing Agricultural University. When he returned to Shanxi to start his lab, he focused on using beneficial bacteria to rein in plant pathogens. One day, a veterinary scientist colleague asked for some strains of Bacillus, explaining that the bacteria helped control diarrhea in pigs and chickens. Zhao realized he was sitting on bacterial strains that might control infections in humans as well as plants.

Throughout the 1990s, Zhao dabbled in research on the pig microbiome, exploring the idea that bacterial strains might control infections in pigs, but couldn't get funding. Meanwhile, his family's health was falling apart. His plump father's cholesterol levels spiked, and the elder Zhao suffered two strokes. Zhao's two brothers had become obese as well. A few years later, Gordon's paper provided what Zhao calls “the first evidence that gut microbiota can actually regulate host genes.” Thus it seemed plausible that this was a way the microbiome could affect health. He began using himself as a guinea pig to try to pin down what microbes might be involved in weight gain. Early microbiome research had raised more questions than it answered, however, and figuring out which of the hundreds of microbial species living in the average human gut might be involved was tricky.

He dug into Western literature on weight loss, but introducing a low-calorie diet and strenuous exercise didn't make sense to him. “Nutritionally, your body is under stress,” he says. “Then you add to that physical stress. Maybe you can lose weight, but you might also damage your health.” Zhao thought of his father's herbal concoctions and turned instead to the traditional medicine literature for inspiration.

Obesity and diabetes plagued members of China's imperial court thousands of years ago, and the diagnoses of early doctors preserved in ancient materia medica resonated with Zhao. Traditional doctors “don't have any idea about gut microbiot

热点，过几年会有很多成果出现。赵立平的结果不是发表在Science,是对他的采访发在那儿。小心你老婆找不着拾掇你。上海原来两所医学院的斗争还是激烈的，当然竞争也有好处。我在北京，好像三所医学院校并没有太多争斗，不过我那时是学生，就算上层有斗争，我也不会知道，扯远了。

有人说他们的统计有问题，文章中的图怎么怎么。肘子又是没有大眼光，盯得都是小问题。其实肠道菌群的测定都是通过检查粪便。可是这种检查有时会有问题，因为粪便里的菌群会随着饮食的变化，饮水的多少产生变化。所以用粪便菌群代表肠道菌群会有一定问题，至少不会太准，但大趋势不会错。所以他们的数据统计学差异可能没那么好。只有多次取粪便样，多次培养然后取均值，可能会更好，这在临床上又不好操作。谁没事呆在医院不停便便让你多次采样。

上海另外一个研究提到小波碱的作用，而北京的研究证明黄连的同类效应，不同的临床研究得出相似的结果，我认为可信。中药消渴丸也是苦寒类药物，小波碱的含量较高。苦瓜也有很高的小波碱，所以赵立平推荐他。

咱们的中药汤字，可能很多就是通过调节肠道菌群来起效。这也 给中药研究开辟了一个新思路。