看不见的宇宙：微生物概论 | The Invisible Universe: Introduction to Microbes

第 1 章：看不见的宇宙：微生物概论

The Invisible Universe: Introduction to Microbes

想象一个场景：此刻，你正坐在教室里，阳光透过窗户洒在课桌上，空气中似乎一片宁静。然而，在这看似平静的表面之下，在你看不见的世界里，一场波澜壮阔的生命盛宴正在如火如荼地进行着。数以万亿计的微小生物正在你的皮肤上“安营扎寨”，在你的肠道里“繁衍生息”，在你的口腔中“谈笑风生”。它们小到几乎无法被肉眼捕捉——一个细菌的直径通常只有头发丝粗细的百分之一——却又数量庞大到足以构成你身体重量的一大部分。这，就是微生物的世界。

Now, imagine this: You are sitting in a classroom, sunlight streaming through the window onto your desk. The air seems peaceful and calm. But beneath this seemingly tranquil surface, in a world invisible to your eyes, a magnificent feast of life is unfolding. Trillions of microscopic organisms are "setting up camp" on your skin, "multiplying" in your intestines, and "chatting" in your mouth. They are so small that they can barely be seen by the naked eye—a bacterium's diameter is typically about one-hundredth the thickness of a human hair—yet their numbers are so vast that they constitute a significant portion of your body weight. This, is the world of microbes.

微生物学（Microbiology）作为一门专门研究这些微小生命的学科，已经发展了三百多年。从1676年荷兰商人安东尼·范·列文虎克（Antonie van Leeuwenhoek）首次用自制的显微镜观察到“微动物”（animalcules）开始，到如今人类已经绘制出肠道微生物组的完整基因图谱，我们对微生物世界的认知经历了翻天覆地的变化。但即便如此，这个看不见的宇宙仍然充满了未解之谜，等待着新一代的科学探险家去揭开它的神秘面纱。

Microbiology, the discipline dedicated to studying these microscopic life forms, has developed over more than three centuries. From 1676 when Dutch merchant Antonie van Leeuwenhoek first observed "animalcules" using a self-made microscope, to today when humanity has mapped the complete genetic blueprint of the gut microbiome, our understanding of the microbial world has undergone tremendous changes. Yet even so, this invisible universe remains full of unanswered questions, waiting for a new generation of scientific explorers to uncover its mysteries.

微生物的数量：一场数字的革命

The Microbial Count: A Numerical Revolution

在正式踏上这趟微生物探索之旅之前，让我们先来完成一个至关重要的认知校准：我们究竟有多少微生物？

Before embarking on this journey of microbial exploration, let us first accomplish a crucial cognitive calibration: exactly how many microbes do we have?

2016年，一项发表在《自然》杂志上的研究彻底颠覆了人们的传统认知。来自以色列和加拿大的科学家团队经过精密计算后发现，人体中微生物细胞的数量约为38万亿（$3.8 \times 10^{13}$），而人体自身细胞的数量约为30万亿（$3.0 \times 10^{13}$）。这意味着，在你身体的每一个角落，微生物的数量都略微超过了你自己的细胞。

In 2016, a study published in *Nature* completely overturned traditional understanding. A team of scientists from Israel and Canada, after meticulous calculations, discovered that the human body contains approximately 38 trillion ($3.8 \times 10^{13}$) microbial cells, while the human body itself has approximately 30 trillion ($3.0 \times 10^{13}$) cells. This means that in every corner of your body, the number of microbes slightly exceeds that of your own cells.

这个比值约为 1.3:1，也被称为“微生物比”（microbiome ratio）。这意味着，从细胞数量的角度来看，你其实只有不到一半是“人类”的自己。更令人惊讶的是，当我们进一步分析基因层面时，这个比例变得更加悬殊：人类基因组大约包含 20,000-25,000 个基因，而人体微生物组所携带的基因数量高达 200万至2000万 个——是你的基因数量的 100到1000倍！

This ratio of approximately 1.3:1 is also called the "microbiome ratio." This means that from the perspective of cell count, less than half of you is actually "human." What is even more surprising is that when we analyze at the genetic level, this ratio becomes even more staggering: the human genome contains approximately 20,000-25,000 genes, while the human microbiome carries 2 million to 20 million genes—100 to 1,000 times more than your own genes!

这一发现的意义远超数字本身。它迫使我们重新思考一个根本性的问题：究竟什么是“人类”？如果构成我们身体近一半的细胞来自微生物，如果控制我们生理功能的基因大多数来自微生物，那么“我们”与“他们”之间的界限究竟在哪里？

The significance of this discovery extends far beyond mere numbers. It forces us to rethink a fundamental question: what exactly is "human"? If nearly half of the cells comprising our bodies come from microbes, if most of the genes controlling our physiological functions come from microbes, then where exactly is the boundary between "us" and "them"?

这种思考方式催生了一个革命性的概念——“全息人类”（Hologenome）。这个概念由进化生物学家尤金·罗森伯格（Eugene Rosenberg）在2008年提出，它将宿主生物及其相关微生物群视为一个单一的功能单元。正如罗森伯格所言：“动物是宿主和微生物群的共生整体，我们称之为全息生物（holobiont）。”从这种视角来看，新冠病毒（ SARS-CoV-2 ）对人类的影响，本质上是与人类全息生物的一场“对话”。

This way of thinking gave birth to a revolutionary concept—the "Hologenome". Proposed by evolutionary biologist Eugene Rosenberg in 2008, this concept treats the host organism and its associated microbial community as a single functional unit. As Rosenberg stated: "Animals are symbiotic complexes of host and microbes, which we call holobionts." From this perspective, the impact of SARS-CoV-2 on humans is essentially a "conversation" with the human holobiont.

微生物的分类王国：从细菌到病毒

The Kingdom of Microbial Classification: From Bacteria to Viruses

既然微生物在我们身体中扮演着如此重要的角色，那么让我们来认识一下这个大家族的主要成员。微生物是一个极为宽泛的概念，涵盖了所有肉眼不可见、需要借助显微镜才能观察的生物。根据现代生物分类学，微生物主要包括四大类群：细菌（Bacteria）、真菌（Fungi）、原生动物（Protozoa）和病毒（Viruses）。

Since microbes play such important roles in our bodies, let us get acquainted with the main members of this large family. Microorganisms are an extremely broad concept, encompassing all organisms invisible to the naked eye and requiring microscopy for observation. According to modern biological taxonomy, microorganisms mainly include four major groups: Bacteria, Fungi, Protozoa, and Viruses.

细菌：地球最古老的幸存者

Bacteria: Earth's Most Ancient Survivors

细菌是微生物世界中最庞大、最多样化的类群。它们是单细胞生物，没有细胞核结构，属于原核生物（Prokaryotes）——这一术语来自希腊语"prokaryote"，意为“原始的核”（pro = before, karyote = nucleus/kernel）。

Bacteria are the largest and most diverse group in the microbial world. They are single-celled organisms without a nuclear structure, belonging to Prokaryotes—a term from Greek "prokaryote," meaning "primitive nucleus" (pro = before, karyote = nucleus/kernel).

细菌的形态多种多样，主要可以分为几种基本形状：

Bacteria come in diverse shapes, which can be categorized into several basic forms:

| 形态类型 | 英文名称 | 拉丁语词根 | 典型代表 | 直径/大小 | |---------|---------|-----------|---------|----------| | 球形 | Cocci | coccus (berry) | 葡萄球菌、金黄色葡萄球菌 | 0.5-1.0 μm | | 杆形 | Bacilli | bacillus (small rod) | 大肠杆菌、炭疽杆菌 | 0.5-1.0 × 1.0-5.0 μm | | 螺旋形 | Spirilla | spirillum (coil) | 幽门螺旋杆菌 | 0.5-1.0 × 5.0-40 μm | | 弧形 | Vibrios | vibrio (vibrate) | 霍乱弧菌 | 0.5-0.8 × 1.0-3.0 μm |

*μm = 微米（micrometer），1微米等于0.001毫米*

细菌的细胞结构虽然简单，却蕴含着惊人的生存智慧。细胞壁（Cell Wall）是细菌的“铠甲”，主要由肽聚糖（Peptidoglycan）构成，这种网状结构为细菌提供了强大的机械保护。革兰氏染色法（Gram Staining）正是基于细菌细胞壁结构的差异，将细菌分为革兰氏阳性菌（Gram-positive）和革兰氏阴性菌（Gram-negative）两大类，这一分类在医学诊断中具有重要意义。

Although bacterial cell structure is relatively simple, it contains astonishing survival wisdom. The cell wall serves as the bacteria's "armor," primarily composed of peptidoglycan, a net-like structure that provides powerful mechanical protection. The Gram staining method, based on differences in bacterial cell wall structure, classifies bacteria into two major categories: Gram-positive and Gram-negative bacteria—a classification of great significance in medical diagnosis.

一个著名的案例是大肠杆菌（*Escherichia coli*，简称 *E. coli*）。这种生活在哺乳动物肠道中的杆状细菌，是最早被人类完整基因组测序的生物之一（1997年完成）。大肠杆菌的基因组仅包含约 4,600 个基因，却能够高效地完成营养代谢、DNA复制、蛋白质合成等复杂生命活动。更令人称奇的是，科学家们已经将大肠杆菌改造成了“活的工厂”——它可以生产胰岛素、干扰素、疫苗抗原等重要药物分子，如今全球约 80% 的重组胰岛素都来自转基因大肠杆菌。

A famous example is *Escherichia coli* (*E. coli*), a rod-shaped bacterium living in the intestines of mammals. It was one of the first organisms whose complete genome was sequenced (completed in 1997). The *E. coli* genome contains only about 4,600 genes, yet it efficiently performs complex life activities such as nutrient metabolism, DNA replication, and protein synthesis. Even more remarkable is that scientists have transformed *E. coli* into a "living factory"—it can produce important pharmaceutical molecules such as insulin, interferon, and vaccine antigens. Today, approximately 80% of recombinant insulin worldwide comes from genetically modified *E. coli*.

然而，并非所有细菌都是人类的朋友。金黄色葡萄球菌（*Staphylococcus aureus*）就是一种危险的致病菌，它能引起从皮肤感染到败血症等多种疾病。2010年，研究人员在印度、巴基斯坦和英国发现了携带 NDM-1基因（New Delhi metallo-beta-lactamase 1）超级细菌，对绝大多数抗生素具有耐药性，为全球公共卫生敲响了警钟。

However, not all bacteria are friends of humans. *Staphylococ