益生菌还是益生元？探索“肠道”健康的复杂世界

编辑翻译：菁菁

译文校对：奇奇

本文献于2021年首次发表在最新的《科学进展》（Science Advances）。文献中研究人员探索了“肠道世界”中的微生物群落与人体健康的关系。

在健康人群体内，有益菌和有害菌能够保持良好的平衡。但当人们生病时，这一平衡会被打破。因此，为了提高有益菌水平，许多人选择服用益生菌补充剂——含有活菌的药物。当前，有众多益生菌商品可供消费者购买。专家对它们的安全性普遍认可，关于功效则意见并不统一。

用于识别胃肠道主要功能的非侵入性方式的说明。

在人体内有一大型的微观群落，称为微生物组。数万亿细菌在这个群落中不断进行“拔河”，以维持有益菌和有害菌的平衡。由于细菌有助于消化食物且能够支持免疫系统，大多数这样的斗争发生在人体的肠道内。专家认为良好的肠道状况对于一个人的健康和生活质量至关重要。但关于肠道内部的具体情况，科学家们仍在探索中。

密苏里大学化学系教授Elena Goun表示：“鉴于肠道菌群独特的化学环节、 可变的分布、高度动态的特性，到目前为止，我们还没有任何方法可以无创地监测完整胃肠道的活动。”

发表在《科学进展》上的一项新研究表明，Goun和一个国际科学家团队开发了一种非侵入性的诊断成像工具，用于测量人体整个肠道中天然存在的酶（胆汁盐水解酶）的水平。Goun表示，这一工具有三个主要功能：

预测炎症性肠病（例如克罗恩氏病和溃疡性结肠炎）的临床状况。

通过测试胆盐水解酶的水平来确定市售益生菌补品的功效，该盐能够对益生菌的全部主要健康促进功能进行产生反应。

评估一些类型的益生元（如有益消化健康的膳食纤维）是否能以类似于益生菌补品的方式提升胆汁盐水解酶的水平。

Goun擅长开发生物医学成像工具，以增进对人类疾病过程的认识和理解。他认为这一研究发现是令人振奋的，尤其是与益生元有关的发现。益生元可以天然存在于全谷物、坚果、种子、水果、蔬菜等食品中。

Goun说：“益生元通常与益生菌结合使用以增强其功效。我们首次证明，仅单独使用某些类型的益生元就能增强肠道菌群的胆汁盐水解酶活性。除其他健康益处外，研究还显示它可以减少炎症，降低血液中的胆固醇水平，并预防结肠癌。在我看来，这个发现的意义是重大的。因为益生元的生产和存储比益生菌更便宜。”

先前的研究指出，胃肠道胆汁盐水解酶的高活性意味着更好的消化健康状况和无炎症。Goun说，他们的非侵入性方法使用生物发光（通过一种化学反应在活生物体内产生光）来测量整个胃肠道中胆汁盐水解酶活性的水平。

Goun说：“我们的成像工具是胶囊式的生物发光探针。当有人吞咽它时，它会在整个肠道旅行。在这一恶劣环境中，探针暴露于完整的肠道菌群。它从体内出来后，我们可以分析一个人的粪便样本。我们可以从该分析中取得结果，并将其与人类胃肠道内胆汁盐水解酶活性联系起来。”

Goun认为，这项研究为科学家提供了一种新的方法，有助于更好地了解一个人的肠道健康与其病理因素的关系，或人类疾病起源和本质之间的联系，进而带来更好的精准医学治疗方案。

Goun说：“这是首个在人体内成功使用生物发光成像探针的案例。肠道微生物组在诸如癌症、糖尿病、肥胖症、帕金森氏病、抑郁症、自闭症等各种健康问题中扮演着重要的角色。现在这种新工具将帮助我们更好地了解肠道功能与这些疾病之间的关系。此外，这有助于我们开发出更有效的益生菌和益生元，以改善肠道健康。”

密苏里大学系统的“新一代精准健康”计划彰显了个性化医疗保健的前景，以及大规模跨学科合作的影响。该系统的四所研究型大学的创新学者聚在一起，以推进能够改变生活的精准健康发展。这是一项协作研究，旨在利用密苏里大学以及整个密苏里大学系统的优势，为该州的健康创造更美好的未来。该计划的重要组成部分是建设新的“新一代精准健康”大楼，它将使用最先进的研究设施并扩充研究人员队伍，并促进临床医生和行业领导者之间的合作。

文献原题为“无创成像和胆汁盐水解酶活性的定量：从细菌到人类”，发表在《科学进展》上。

英语原文

Noninvasive Imaging and Quantification of Bile Salt Hydrolase Activity: From Bacteria to Humans

A healthy person has a general balance of good and bad bacteria. But that balance is thrown off when someone gets sick. So, to help boost their levels of good bacteria, many people take probiotic supplements—live bacteria inside of a pill. Various commercial probiotic supplements are available for consumer purchase, and while health experts generally agree about their overall safety, controversy surrounds their efficacy.

Inside the human body lives a large microscopic community called the microbiome, where trillions of bacteria engage in a constant "tug of war" to maintain optimal levels of good and bad bacteria. Most of this struggle takes place within the body's gastrointestinal tract, as bacteria help with digesting food and support the immune system. Although health experts believe good "gut" health is key to a person's health and well-being, scientists are still developing a detailed picture of what goes on inside a person's gastrointestinal tract.

"Until now, we have not had any ways to noninvasively monitor activity in the intact gastrointestinal tract, given the unique chemical environment, variable distribution and highly dynamic nature of the gut microbiota," said Elena Goun, an associate professor in the Department of Chemistry at the University of Missouri.

In a new study published in Science Advances, Goun and an international team of scientists have developed a noninvasive diagnostic imaging tool to measure the levels of a naturally occurring enzyme—bile salt hydrolase—inside the body's entire gastrointestinal tract. Goun said their tool accomplishes three major functions:

Predicts the clinical status of inflammatory bowel disease, such as Crohn's disease and ulcerative colitis.

Determines the efficacy of many commercially available probiotic supplements by testing for the level of bile salt hydrolase, which is responsible for all of the major health-promoting functions of probiotics.

Evaluates whether certain types of prebiotics—dietary fibers known to support digestive health—can increase bile salt hydrolase levels in a similar way that probiotic supplements do.

Goun, who specializes in the development of biomedical imaging tools to advance the knowledge and understanding of various processes underlying human diseases, believes their findings are exciting, especially with the discovery related to prebiotics, which can be naturally found in foods such as whole grains, nuts and seeds, and fruits and vegetables.

"Prebiotics are often used in combination with probiotics to enhance their functions in the body," Goun said. "We show for the first time that certain types of prebiotics alone are capable of increasing bile salt-hydrolase activity of the gut microbiota, which among other health benefits has been shown to decrease inflammation, reduce blood cholesterol levels, and protect against colon cancer and urinary tract infections. In my opinion, this discovery is huge because the production and storage of prebiotics is less expensive than with probiotics."

Previous reports have noted high bile salt-hydrolase activity of the gastrointestinal tract is reflective of better digestive health and a lack of inflammation in the body. Goun said their noninvasive method uses bioluminescence—a chemical reaction that produces light inside a living organism—to measure the level of bile salt-hydrolase activity throughout the entire gastrointestinal tract.

"Our imaging tool is a bioluminescent probe in the form of a capsule," Goun said. "When someone swallows it, it's exposed to the intact gut microbiota while traveling throughout the harsh environment of a person's entire gastrointestinal tract. After it passes out of the body, we can analyze a person's stool sample. We can take the results from that analysis and correlate it with the amount of bile salt-hydrolase activity within the human gastrointestinal tract." 

Goun believes this research could lead to better precision medicine treatments by providing a way for scientists to better understand how a person's individual gut health is connected to various human pathologies, or the origin and nature of human diseases.

"This is the first example of the use of bioluminescent imaging probes in humans," Goun said. "The gut microbiome plays a huge role in various health issues such as cancer, diabetes, obesity, Parkinson's disease, depression and autism, and now, this new tool will help us better understand the relationship between the gut function and these diseases. In addition, it will allow us to develop more effective probiotics and prebiotics to improve gut health." 

Highlighting the promise of personalized health care and the impact of lardge-scale interdisciplinary collaboration, the University of Missouri System's NextGen Precision Health initiative is bringing together innvbators from across the system's four research universities in pursuit of life-changing precision health advancements. It's a collaborative effort to leverage the strengths of Mizzou and entire UM System toward a better future for Missouri's health. An important part of the initiative is the construction of the new NextGen Precision Health building, which will expand collaboration between researchers, clinicians and industry leaders in a state-of-the-art research facility.

"Noninvasive imaging and quantification of bile salt hydrolase activity: from bacteria to humans" was published in Science Advances.

参考文献

Pavlo V.Khodakivskyi et al. Noninvasive imaging and quantification of bile salthydrolase activity: From bacteria to humans, Science Advances (2021). DOI:10.1126/sciadv.aaz9857-

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