An introduction to the human microbiome and its importance for human health.
Written by: Kavya, Haritha, Akshaya
Your body is less human than you think. This is because our bodies consist of more microbial cells than our own human cells. An average human is a habitat for more than 100 trillion microbial cells as compared to 37 trillion human cells (1). It’s even more fascinating that these microbial communities, known as the microbiome (micro - ‘small’, biome- ‘environment’) vary from person to person (like a fingerprint). People who live together tend to have similar microbiome compositions as compared to others. The human microbial community develops from birth and undergoes dynamic changes throughout our lifetimes. In recent years, research has revealed the importance of the microbiome in human development and function. In the next series of articles, we will explore the human microbiome in detail and discuss the latest research on diseases and their connection to the microbiota.
First off, let’s start off by defining a few terms, microbiota and microbiome. Microbiota refers to the different types of microbes present whereas microbiome defines the microbes and their genetic material. These terms are used interchangeably in many sources. When talking about microbiota, phylogenetics is a topic that cannot be avoided. A phylogenetic tree maps the relationship between different species of organisms, in other words, the evolutionary relationship. When we talk about microbes, it is more common to refer to the ends of the tree as taxa rather than species (8). In the picture below, both these trees represent the same evolutionary relationships. A and B are referred to as sister taxa as they are most closely related to each other. A and B together are sister taxa to C. Tree X and Y show that A and B share a common ancestor, where they merge (represented by the star). Further back in time, we can see that A and B’s common ancestor emerged from a common ancestor of C (represented by the square) (8). These relationships are represented in various ways. We wanted to provide an overview of the phylogenetic tree as we might discuss it further in future articles.
What is the microbiota made of?
Our microbiota primarily consists of bacteria, viruses, and fungi. Let’s see what the main differences between these groups are.
Bacteria: Bacteria are tiny, single-celled microorganisms. They are a vital component of ecosystems (2). There are both ‘good’ and ‘bad’ bacteria that can either be beneficial or harmful to our bodies. Bacteria are prokaryotes and they lack a nuclear membrane around their genetic material. Their DNA is found freely in the cytoplasm or in plasmids, which are small DNA molecules within the cell that can replicate independently.
Virus: Viruses are neither living nor non-living. They use the host cells in order to replicate and produce multiple viruses. Viruses are made up of either DNA or RNA and they can be double-stranded or single-stranded (3). They contain a genome that is protected by a protein coat called the capsid, the outermost covering of the virus (7). (refer to our COVID-19 blog 1 and 2 posts for more detail)
Fungi: Fungi can be unicellular or multicellular. They have tough cell walls made of a chemical substance called chitin (4). They grow in moist, acidic environments and they feed on dead, decomposing matter. They can survive with or without oxygen. They reproduce by producing thread-like hyphae, which settle on a new surface and grow into new fungi. Fungi can often be confused with plants, however the main difference is that fungi do not contain chlorophyll whereas plants do (4).
The similarities between all three groups of organisms is that they can all be pathogenic.
How do we characterize the microbes in our bodies?
There are thousands of different bacteria in our microbiota. How do we differentiate between these populations? Why is the differentiation important? The characterization is done by examining their genetic composition. Since bacterial cells replicate rapidly (cloning) and can acquire mutations pretty quickly, it is hard to distinguish between the multiple strains. Therefore, researchers have developed a strategy to define how different strains can be considered a ‘new’ species. This is commonly known as OTU, Operational Taxonomic Unit. If the genetic component is 97% or more similar, then, we consider those microbes to be of the same species. There is a 3% genetic variance that is allowed (1). We need to be able to characterize the different strains in order to isolate the effect they have on our bodies and investigate how we can manipulate them to modify their effects on our bodies.
Can the microbiota change over time? What influences the microbiota?
The microbiome greatly influences the physiology of the host. The different types of microbiota vary in their compositions and functions, which are based on their locations, as well as the age, sex, race, and diet of the host (5).
Let’s discuss how microbiota develop and change over time. Microbiota can consist of commensal bacteria, (commensal meaning an organism which lives inside another and benefits from the host without harming or helping it; commensal bacteria can be found in the intestinal lumen) which enters the host after birth (5). Eventually, it grows into a very diverse ecosystem with the development of the host.The microbiome is shaped by certain host factors which we will now delve into. There are both specific and nonspecific factors that influence the microbiota. We will mainly be using the gut microbiota to show how the host influences the functions and composition, but this is not to undermine the influence our microbiota has on other functions of the body. The gut microbiota is determined by the host with different molecular signals (usually metabolites from the food we eat), which have control of the structures on the surfaces that are colonized by microbiota (which then influences the microbiota’s composition) (6). Apart from nonspecific factors, the composition and structure of the gut microbiota is affected by miRNAs, or non-coding RNAs (6).
As mentioned before, factors including the age and other characteristics of the host affect the microbiota and its homeostasis. They are formed in the beginning of life, but they can change when they are influenced by the development and diversity of the host’s lifestyle (6). Our microbiota starts to develop by the mode of birth and the exposure we gain right after. The way of delivery affects the development of the gut microbiota as well, as newborns delivered through C-section (cesarean delivery) have gut microbiota from the skin and are exposed to less microbes than normal deliveries (6). Even in terms of diet, the composition of the milk the infant takes influences the composition of the early gut microbiota (6). Children who are given milk formula have different microbiota composition than those who are fed human milk. On the other hand, there can be a loss of microbes from the influence of antibiotics, which have both positive and negative influences on the microbiome. The environment we grow up in and the exposure we gain through our interactions shape the microbial composition. This in turns affects our development and health into adulthood.
The microbiome develops in the host from the time of birth and is influenced by many different factors through the growth of the individual. By the time the host is around three years of age, the primary microbiota composition of the child matures, resembling that of an adult microbiota (6). While the microbiota in the host can cause different diseases, they are also essential to the health and development of many systems in the host.
Why should we care about the microbiota?
You might be wondering, why there is so much fuss about the microbiota. Does it really have such a huge influence on our well-being? It’s only within the last couple of decades that microbiota and its involvement in our holistic health have been explored (1). Within this short period of time (for research) the human microbiota has been identified to have an important direct and indirect impact on immune development, disease development (specifically chronic diseases such as diabetes), nutrient absorption, mental well-being (mood, depression, Alzheimer’s), and many more (1). Throughout the next series of blog posts, we will further explore these topics to better understand the importance of the human microbiota and to gain a different perspective on treating human diseases.
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