How the Gut Microbiota Influences Our Health and How We Can Influence It

ABSTRACT 摘要

“眾所周知，人類腸道里的微生物，也被稱為腸道菌群，在我們感覺如何以及我們是否健康或患病中起一定的作用。在大多數情況下，微生物是如何調節身體健康的仍是一個未知數，而通過調控微生物群來改善人們的身體健康的方法也才剛剛開始應用。在這篇文章里，我們將解釋如何研究腸道菌群、我們已經了解到的腸道菌群是如何影響身體健康的，以及已經在使用的或正在研究的方法去影響微生物，以改善人體的健康。”

The microbes in the human gut, also known as the gut microbiota, are known to play a part in how we feel and whether we are healthy or sick. How the microbiota regulates health is still unknown in most cases, and medical treatments to manipulate the microbiota to improve people’s health are only just starting to be used. In this article, we explain how the gut microbiota is currently studied, what we already understand about how the gut microbiota influences health, and ways that are already used, or are being investigated, to influence the microbiota to improve health.

腸道菌群：螺母和螺栓

THE GUT MICROBIOTA: NUTS AND BOLTS

它們在你的身體內，在你身上，是你身體的一部分...它們是微生物！微生物是微小到我們用眼睛無法直接看到的生物體。在我們身體內部和體表上，有著數量大致和人體細胞一樣多的微生物。微生物已經在人類體內聚居了數百萬年，與我們共同進化。在這漫長的相互聯系中，我們與微生物變得相互依賴：我們為微生物提供食物以及它們生活的場所，微生物則反過來為我們服務。我們才開始了解微生物對我們的諸多影響，但有一些令人感到驚訝的例子：它們幫助我們消化食物、訓練我們的免疫系統以保護我們免受感染、調節我們的食欲，甚至影響到我們是否感到開心或悲傷。我們身體內的微生物大多數生活在腸道里，腸道是你---宿主---與微生物的最大的相互作用點之一。我們把生活在腸道里的所有微生物集合稱為“腸道菌群”。

They are in you, they are on you, they are a part of you … they are microbes! Microbes are organisms so small that we cannot see them with our eyes. On and inside our bodies, we have roughly as many microbes as human cells. Microbes have been colonizing humans for millions of years, and we have evolved together. During this long association, we became dependent on each other: we offer the microbes food and a place to live, and in turn they work for us. We are only beginning to understand the many effects microbes have on us, but there are some surprising examples: they help us digest food, train our immune systems, protect us from infections, regulate our appetites, and even influence whether we feel happy or sad. Most of the microbes in our bodies live in the gut, which is one of the largest interfaces between you—the host—and the microbes. We call the entire collection of microbes living in the gut the?gut microbiota.

生活在腸道里的微生物皆不相同。到目前為止，研究人員已經鑒別了超過2000種生活在人類體內或體表的不同微生物物種。每個人的腸道菌群在物種的數量以及豐裕度上都各不相同，這使得每個人的微生物群都是獨一無二的。

The microbes in the gut are not all the same. So far, researchers have identified more than 2,000 different species of microbes that live in or on humans. Everyone differs in the number and abundance of species in the gut microbiota, which makes the microbiota of each person unique.

腸道菌群從何而來？在嬰兒還未出生前，生活在他們體內或體表的微生物少之甚少。出生時，人類寶寶會與一些微生物朋友第一次相遇，隨著年齡的增長，他們將接觸新的微生物。兒童的微生物群與成年的微生物群是迥然不同的，直至成年，微生物的物種數量都會穩步增加。即使在成年人里，微生物群的組成部分仍可以發生改變，這取決于我們的基因、我們所處的環境以及我們所吃的食物。

Where does the gut microbiota come from? There are few microbes living in or on babies before they are born. At birth, human babies meet some microbial friends for the first time, and they continue picking up new microbes as they grow older. The microbiota of children looks different from that of adults, and the number of species increases steadily until adulthood (Figure 1). Even in adults, the composition of the microbiota can still change it and depends on our genes, the environment we live in, and the foods we eat.

圖1-腸道菌群隨著我們年齡的增長而變化

Figure 1 - The gut microbiota changes as we age.

（A）在新生兒時期，腸道內的微生物少之甚少。隨著孩子的長大，他或她會從其他人或環境中獲取微生物，以形成腸道菌群。

(A)?In newborns, very few microbes are present in the gut. As a child grows older, he or she picks up microbes from other people or the environment, which form the gut microbiota.?

（B，C）腸道菌群會隨著時間的推移而變得更加多樣化。每個人體內微生物的確切組合是獨一無二的，因此每個人的微生物群看起來都不一樣。

(B,C)?The gut microbiota changes and gets more diverse over time. The exact mix of microbes in every person is unique, and therefore everyone’s microbiota looks different.

健康的腸道菌群是什么呢？

WHAT IS A HEALTHY GUT MICROBIOTA?

我們知道擁有一個健康的腸道菌群尤為重要。但健康的腸道菌群是什么呢？盡管許多科學家正竭盡全力地解答這個問題，但要回答這個問題還可謂難上加難。人與人之間，甚至在同一個人身體里，微生物物種的數量以及這些物種的相對豐度是不同的，而且也會隨著時間的推移而變化。此外，體內環境的變化可以將一些微生物物種由無害的居住者變為危險的入侵者。因此，每當腸道中的某些東西發生變化時，數以百計的其他東西也會隨之發生改變，這就使科學家們極難理解這些變化中哪些才是最重要的。

We know that a healthy gut microbiota is important. But what is a healthy microbiota? This is an extremely difficult question to answer, even though many scientists are working hard on solving it. The number of different species and the relative abundances of these species vary between people and even within the same person over time. In addition, changes in the bodily environment can turn some microbiota species from harmless inhabitants into dangerous invaders. As a result, every time something changes in the gut, hundreds of other things change as well, which makes it extremely difficult for scientists to understand which of these changes is actually important.

科學家們是如何研究如此錯綜復雜的系統呢？其中一個方法就是利用老鼠，這些老鼠是在特別干凈的條件下培養的，這樣它們就沒有任何微生物群，但它們依然是健康的?？茖W家們給這些老鼠一些從患病的或健康的人體內分離出來的腸道菌群。如果只是接收了“病人”微生物群的小鼠患病，我們便知道這個疾病是由該微生物群引起的，因為這是老鼠間唯一的區別。知道這個非常重要，但在大多數情況下，我們仍然不理解這是如何發生的。

How do scientists study the function of such a complex system? One way is to use mice that are raised in exceptionally clean conditions, so that they do not have any microbiota, but they are still healthy. Scientists give these mice some of the gut microbiota isolated from either sick or healthy humans. If only the mouse given the “sick” microbiota develops the disease, we know the disease is due to the microbiota, because it is the only difference between the mice. This is important to know, but in most cases, we still do not understand how this happens.

腸道菌群是如何維持我們健康的？

HOW THE GUT MICROBIOTA CAN KEEP US HEALTHY

在某些情況下，我們擁有微生物是如何影響我們的相關解釋。其中一種情況是其與免疫系統的相互作用。腸道里的免疫系統需要防止有危害的微生物免遭其造成疾病。但它不應該對正常的微生物群做出過度反應。免疫系統通過產生平衡的激活信號和停用信號來實現這種狀態。如果平衡被打破，產生的大多數是激活信號，就會導致疾病。科學家們發現，微生物群釋放出的一種被稱為“丁酸鹽”的廢物，可以指示免疫系統制造更多的停用信號，因此，微生物群有助于維持這種平衡，防止免疫系統過度反應。

In some cases, we have explanations for how the microbiota affects us. One such case is its interaction with the immune system. The immune system in the gut needs to prevent dangerous microbes from causing disease, but it should not over-react to the normal microbiota. The immune system achieves this state by producing a balance of activating and de-activating signals. If the balance is disturbed and mostly activating signals are produced, disease can result. Scientists have discovered that a waste product released by the microbiota, called butyrate, can instruct the immune system to make more deactivating signals. The microbiota thus helps keep the balance and prevents the immune system from overreacting [1].

第二種情況是微生物群在預防腸道感染中的作用。如果你吃的食物或飲用的水中含有能讓人致病的微生物（沙門氏菌可能是你曾聽說過的這樣一種微生物），實際上在大多數情況下你仍保持健康。這往往是由于你的腸道菌群可以通過產生能夠殺害入侵者的物質直接與它們對抗，通過刺激你的免疫系統增強你對有害細菌的抵抗力，通過消耗掉所有可供的食物使得留給侵入者的食物幾近于無。

A second case in which we have some understanding of how the microbiota affects us is the role of the microbiota in preventing gut infections. If you eat food or drink water containing microbes that can make you sick (Salmonella?is one such microbe that you might have heard of), in many cases you actually stay healthy. This is often due to your gut microbiota, which can directly fight the invaders by producing substances that can harm them, by stimulating your immune system to increase your resistance to harmful bacteria, and by consuming all the available food so nothing is left for the invaders [2].

第三種情況是微生物群從我們的食物中采集能量所扮演的角色。你是否曾聽說過膳食纖維這個詞？膳食纖維富含在蔬菜水果中，含有大量的能量。但這些能量不能被我們身體所利用，因為我們沒有提取它們的機器。然而，腸道菌群就有這臺機器，微生物群可以消化膳食纖維，釋放一些能量供我們利用。在這種情況下，你的微生物群會生產出你每天利用的能量的10%。如果在食物不充裕的情況下，這是生存的一個重要要素，但如果周圍的食物太多，這個過程會潛在地導致人變胖。

A third case is the role of the microbiota in harvesting energy from our food. Have you heard the term dietary fiber? Dietary fiber is abundant in fruits and vegetables, and it contains a lot of energy. But this energy cannot be used by our bodies because we do not have the machinery to extract it. However, the gut microbiota has this machinery, and the microbes can digest dietary fiber, releasing some of the energy for us to use. In this way, your microbiota produces 10% of the total energy that you use every day [3]. This is an important factor for survival if there is not enough food, but if there is too much food around, this process can potentially contribute to people becoming overweight.

調控腸道菌群的方式

WAYS TO MANIPULATE THE GUT MICROBIOTA

一個健康的微生物群對我們身體的一些主要功能十分重要。但即便我們的腸道菌群是健康的，像有危害的細菌的入侵事件或抗生素的使用都可以劇烈地改變它。在某些情況下，腸道菌群的這些變化可導致疾病。

在過去的十年里，人們已經發現了保持一個健康的微生物群或調控微生物的組成部分的方法。還有一些有助于促進特有微生物和抑制已知的有危害的微生物的干預措施。以下是諸如此類的三種干預措施。（參見圖2）

A healthy gut microbiota is important for some of the main functions of our bodies. But even if our microbiota is healthy, events like the invasion of dangerous bacteria or the use of antibiotics can dramatically change it. In some cases, these changes to the gut microbiota can cause diseases.

In the last decades, ways to help us keep a healthy microbiota or to manipulate the microbiota’s composition have been discovered. There are also interventions that help to promote specific beneficial microbes and to inhibit ones known to be dangerous. Here are three such interventions (also see?Figure 2).

圖2-操控腸道菌群以改善健康

Figure 2 - Manipulating the gut microbiota to improve health.

（A）益生元是食物中可以專門喂養希望得到的微生物的養分。有益的微生物就會在腸道內增加，從而改變微生物群，有望消除不需要的微生物。

(A)?Prebiotics are components of food that can specifically feed desired microbes. The beneficial microbes will then increase in the gut, which will change the microbiota, hopefully eliminating the undesired microbes.?

（B）糞菌移植將健康人的腸道菌群轉移到病人的腸道中。這些移植可以很好地治療一種叫艱難梭菌的有危害的細菌的感染。

(B)?Fecal microbiota transplants put a healthy person’s gut microbiota into a sick person’s gut. These transplants can work well for treating infections with a dangerous bacterium called?C. difficile.

（C）針對微生物群中單一類型的微生物進行疫苗接種，可以訓練免疫系統產生針對這種微生物的抗體，從而幫助身體排出不希望得到的微生物。

?(C)?Vaccination against a single type of microbe in the microbiota can train the immune system to make antibodies against this microbe, which helps the body to flush out the undesired microbes.

益生元?Prebiotics

不同的微生物對食物的偏好各不相同。維持有益微生物生計的其中一種方式是通過給它們提供它們最愛吃的食物來幫助它們生長。這些它們喜愛的膳食纖維物質被稱為“益生元”。例如，有些種類的有益細菌喜歡吃某種類型的膳食纖維。要想理解它，我們可以把它想像成一場賽車比賽，不同類型的車所需的燃料種類各不相同。食用益生菌就像只給你想贏的汽車提供燃料（有益細菌），而不給其他細菌提供燃料。

Different microbes have different food preferences. One way of supporting beneficial microbes is to help them grow by providing them with the foods they like best [4]. These preferred dietary substances are called?prebiotics. For example, some species of beneficial bacteria like to eat a certain kind of dietary fiber. One way to think about this would be as a car race, with different cars needing different kinds of fuel. Eating prebiotics is like giving fuel only to the cars you want to win (the beneficial bacteria), while not fueling the others.

糞便移植Fecal Transplantation

改變微生物群的另一種方式是將一個健康人（捐贈者）的腸道菌群轉移到病人（接收者）體內。這種方式被稱為“糞菌移植”，你可以聯想一下，它就像把一支踢得不好的足球隊換成另一支球隊一樣。糞菌移植是從捐贈者的糞便中提取出腸道菌群，通過吞服藥片或經過鼻子或直腸的管狀器官將其轉移到接收者的腸道里。你不覺得這很吸引人嗎?這是可以理解的反應!然而，對于一種疾病，糞菌移植似乎十分有用：艱難梭狀芽孢桿菌（簡稱：艱難梭菌）的反復感染。如果腸道菌群受到干擾，這種桿菌就會茁壯生長，從而導致嚴重的疾病。艱難梭菌可通過抗生素將其消滅，但它們對抗生素耐藥性十分普遍，通常來說當病人停止服用抗生素時，疾病就會復發。糞菌移植可治愈80%～90%遭受此疾病的人，通常而言是安全的。然而，糞菌移植常常以一種不可預見的方式影響接收者的腸道菌群。

Another way to change the microbiota is the transfer of the gut microbiota from a healthy person (the donor) to a sick one (the recipient). This is called a?fecal microbial transplant, and you can think about it like replacing a soccer team that does not play well together with a different team. A fecal microbial transplant is done by taking the donor’s gut microbiota from their feces, and transferring it into the recipient’s gut, either by swallowing a pill or via a tube through the nose or the rectum. Does not sound very appealing to you? A very understandable reaction! However, for one disease, fecal microbial transplants seem to work extremely well: recurrent infections with?Clostridioides difficile, a microbe that can thrive if the gut microbiota is disturbed, causing a very serious disease.?C. difficile?can be killed by antibiotics, but antibiotic resistance is common, and often the disease comes back when the patient stops taking the antibiotics. Fecal microbial transplants cure 80–90% of people suffering from this disease and they are generally believed to be safe. However, fecal microbial transplantation often influences the recipient’s gut microbiota in an unpredictable way.

精密微生物群工程?Precision Microbiota Engineering

當前的研究聚焦在更有針對性地改變微生物群，以避免糞菌移植中的一些不可預測性。一種可能是針對特定的不需要的微生物進行口服疫苗接種。和其他大多數疫苗一樣，口服疫苗會告訴免疫系統制造出一系列被稱為抗體的蛋白質，它可以黏在目標微生物上。這些抗體將這些微生物黏成一團，使得更容易將其從腸道中清除。為了促進這個過程，我們可嘗試使用另一個技巧：一種與疫苗所針對的微生物非常相似，但又無害的微生物，這種微生物可以與疫苗一起服用。這種微生物被稱為利基競爭者。利基競爭者會使難以對付的微生物的生活變得更加艱難，因為它會與那些微生物競爭食物和生存空間。設想一下，這就像在玩搶座椅游戲一樣：免疫系統與目標微生物保持距離，誰的速度更快、適應性更好，誰就能取代它們的位置。這種策略顯示出了前途無量的結果，目前正對其進行研究，以使其能廣泛運用。

Current research focuses on more targeted changes to the microbiota, to avoid some of the unpredictability of fecal microbial transplants. One possibility is?oral vaccination?against specific unwanted microbes. Like most other vaccines, oral vaccination tells the immune system to make proteins called antibodies that stick to the targeted?microbes. These antibodies glue these microbes together into large clumps, which are easier to flush out of the gut [5]. To help this process, we can use another trick: a microbe that is very similar to the one targeted by the vaccine, but not harmful, can be given with the vaccine. This microbe is called a?niche competitor. The niche competitor makes life even harder for the problematic microbe because it competes with the problematic microbe for food and living space. Imagine this like playing musical chairs: the immune system keeps the targeted microbes at distance and whoever is faster and better adapted can take their place. This strategy shows promising results, and research is underway to make it broadly usable.

帶回家的信息（總結）

TAKE-HOME MESSAGE

我們才剛剛開始了解腸道菌群影響你的健康的方式，但我們已經知道了它有著強有力的影響，以及可以用巧妙的方法影響它。了解腸道菌群的作用是研究中的高度活躍領域。世界各地的團隊正努力界定什么樣的特性會使微生物群“健康”或“患病”，另一些團隊則在繼續研發技術，使微生物群發生精確變化。這項研究將進一步揭露人類與微生物之間的復雜關系，并將為改善許多人的健康和生活質量帶來更好的方法。

We are only beginning to understand the ways in which the gut microbiota influences your health and well-being, but we already know it has a strong effect and that there are smart ways to influence it. Understanding the role of the gut microbiota is a highly active area of research. As some groups around the world work to define what characteristics make a microbiota “healthy” or “diseased,” others are continuing to develop techniques to make precise changes in the microbiota. This research will shed more light on the complex relationships between humans and microbes, and will lead to better ways for improving the health and quality of life for many people.

Glossary?術語表

Microbes:?↑?All living things that are not visible by the naked eye are called microbes. They are found in most places on earth, and perform important functions in the environment and for our health, but some microbes make us sick.

微生物群：凡是肉眼看不到的生物都叫微生物。它們可在地球上大多數地方被發現，它們在環境中發揮著重要的功能，對我們的健康也有重要的作用，但有些微生物會讓我們生病。

Gut Microbiota:?↑?The community of microbes that lives in our digestive tract, one of the densest microbial communities on the planet.

腸道菌群：生活在我們消化道中的微生物群落，是地球上最密集的微生物群落之一。

腸道菌群：

Prebiotics:?↑?Components in food that specifically feed beneficial members of the gut microbiota, to promote them over other species.

益生元：食物中專門喂養腸道微生物群有益成員的組成成分，以促進它們（在數量上）超過其他物種。

Fecal Microbial Transplant:?↑?The transfer of the gut microbiota in the feces of a healthy person to a person with a disturbed gut microbiota. This technique is currently used for treating recurrent?C. difficile?infections.

糞菌移植：將健康人糞便中的腸道微生物群轉移到腸道微生物群受到干擾的人身上。這種技術目前用于治療艱難梭菌的周期性感染。

Oral Vaccination:?↑?Training the immune system to react against specific microbes by swallowing the killed microbe, or parts of the microbe.

口服疫苗：通過吞食被殺死的微生物或部分微生物來訓練免疫系統對特定的微生物做出反應。

Niche Competitors:?↑?Members of a biological community that need the same resources (live in the same ecological niche) and are in direct competition for them.

利基競爭者：一個生物群落的成員需要相同的資源(生活在相同的生態位上)，它們會直接競爭這些資源。

原文出處：https://kids.frontiersin.org/articles/10.3389/frym.2021.576428