Exploring the mysteries of the human microbiome

The human microbiome plays a vital but little-understood role in our overall health, including affecting our longevity and even mental health.
Tejasri Gururaj
An artists' conception of the human microbiome.
The human microbiome is the genetic material of all the microbes that live on and inside the human body.

Design Cells 

  • The human body is host to millions of micro-organisms.
  • Together these make up the human microbiome.
  • Scientists now believe the human microbiome plays an important role in our physical and mental health.

Would you be terrified to learn that there were millions of organisms living in and on your body? Let's hope not, because right now, your body is host to millions of microbes such as bacteria, fungi, and viruses. These are collectively called the human microbiome or human microbiota. 

The organisms of the microbiota inhabit various parts of our bodies, such as the skin, mouth, gut, and reproductive organs. The human microbiome is very intricate, with some microbes assisting with various body functions, but the precise role of the majority of them is not known.

For a long time, it was assumed that the ratio of microbes to human cells was around 10:1, based on estimates by microbiologist Thomas Luckey. However, in 2016, a study led by Ron Sender from the Weizmann Institute of Science in Israel, estimated the ratio of microbial-to-human cells to be closer to 1:1.

In a review study led by Jack A Gilbert from the University of Chicago, the estimate was 1.3:1 for the ratio of bacterial cells to human cells, with the number of viruses and phages outnumbering the bacterial cells by at least a factor of 10. 

Exploring the mysteries of the human microbiome
The bacteria Lactobacillus in the human intestine.

We know very little about this rich ecosystem, to say the very least. But we do know that the microbiota plays an important role in maintaining overall health and performing certain functions in the human body.

So let's explore our current understanding of the human microbiome, its role, and the future of microbiome research.

The human microbiome

Microbes are present in many different parts of our body, with their numbers and composition varying from site to site. But let's first understand the difference between the terms microbiota and microbiome. 

While the two terms are generally used interchangeably, there are differences between them. Microbiota refers to a set of living microorganisms present in a specific site or habitat. In the human body this might be areas such as the gut, stomach, or lungs.

On the other hand, microbiome can also refer to all the genetic material of microorganisms in a given environment, taking into account environmental factors, community, structures, and metabolites. This basically means that the term microbiome is often used to encompass a broader spectrum than microbiota.

Exploring the mysteries of the human microbiome
Some of the microbes found in the human body.

Antonie van Leeuwenhoek, a Dutch microscopist, was the first to observe bacteria and protozoa, in around 1632. His observations helped lay the foundations for the study of microbiology. Later, the work of Russian scientist Sergei Winogradsky, in the 1800s, developed microbial ecology as a field of research and examined the underlying concept and importance of the microbiome. He created the Winogradsky Column, a culturing device that permited researchers to study microbes as they interact with each other and with other organisms in a natural setting.

However, due to recent advances in technology we have more recently made significant progress towards understanding the intricate world of the microorganisms that inhabit our bodies. 

According to a study by Elizabeth A. Grice and Julia A. Segre from the National Institutes of Health in Maryland, the human microbiota, what has been called the "hidden organ", constitutes 90 percent of the total number of cells associated with our bodies.

The role of these microorganisms are varied and help determine various physiological aspects of our well-being, which will be discussed in the coming section.

A delicate balance 

Despite the varied microbiota present in our bodies, each serves a unique purpose, impacting our health and wellbeing. 

The gut's microbiome is extremely sensitive and is thought to play a significant role in maintaining gut health, overall health, and possibly also some aspects of mental health.

The most commonly studied gut microorganisms are bacteria, such as bacteroidesFirmicutes, Actinobacteria, Proteobacteria, and Fusobacteria; and fungi such as C. albicans. These play a role in regulating digestion, helping with the fermentation of food, nutrition absorption, and vitamin production. 

Exploring the mysteries of the human microbiome
A wide variety of micro-organisms co-exist in the human gut.

Gut microbiota can also generate nutrients from substrates that are otherwise indigestible by humans. For example, the digestion of xyloglucans, a complex carbohydrate found in lettuce and onions, was recently linked to a particular species of Bacteroides.

Recent research has shown that gut bacteria also play an important role in colorectal cancer. In an article published in Nature, Sarah DeWeerdt discusses studies involving mice that have shown that transferring the gut microbiome from colorectal cancer patients into germ-free mice resulted in fewer tumors when the mice were later exposed to a chemical mutagen that causes colorectal cancer — a counterintuitive result that puzzled the researchers and indicated the link between gut microbiome and disease may not be straightforward. 

The second largest microbial community in the human body is the oral microbiota. These inhabit various parts of the oral cavity, such as the tongue, teeth, saliva, gums, palate, etc. These habitats can undergo significant and rapid changes in their composition and activity due to factors like pH fluctuations, gene mutations, and interactions among the bacteria.

The oral microbiota plays a role in maintaining oral as well as systemic health, and microbial imbalances have been linked to some types of oral and systemic disease. Other sites where microbiota commonly exist include the lungs, human skin, and vagina.

Exploring the mysteries of the human microbiome
Some of the microbiota of the respiratory and gastrointestinal tracts.

New research has also shown a large number of microbes coexisting in the lungs and airways. 

In healthy individuals, the makeup of the lung microbiome is influenced by the more or less constant entry and removal of microorganisms. However, in cases of severe lung disease, the composition of the lung microbiome tends to be primarily influenced by specific local conditions that promote the growth of certain microorganisms. 

The microbiota of the human skin varies depending on the action and condition of the glands and hair follicles, which can depend on factors such as geography and genetics. This creates distinct microbiota whose imbalances may cause skin conditions such as acne and dermatitis. These imbalances can disrupt the natural protective barrier of the skin, leading to inflammation and the proliferation of harmful bacteria, exacerbating skin conditions.

It is the delicate harmony between the microbiome and the host which helps determines the health and functioning of these various organs.

Microbiome diversity

Though the overall species that make up the microbiota in specific areas of the human body don't change a great deal from person to person, several factors can influence the composition of the microbiome.

Exploring the mysteries of the human microbiome
The human microbiome is variable and depends on a number of factors.

A study by Nihal Hasan and Hongyi Yang, from Northeast Forestry University, found that factors such as diet, antibiotics, age, and environment played a huge role in the composition and diversity of the gut microbiota. 

They found that different dietary components, such as fiber, carbohydrates, fats, and proteins, can influence the growth of specific bacterial species. Additionally, antibiotics disrupt the balance of the microbiota by eliminating both the "good" and "bad" bacteria, leading to an imbalance that can contribute to the development of certain diseases. 

The composition of the microbiota can also change with age. The diversity and abundance of microbial species may fluctuate during different stages of life, from infancy, to adulthood, and older age.

In another study, led by Vinod K. Gupta from the Mayo Clinic and the Indian Institute of Chemical Biology (CSIR) in Kolkata, scientists noted that the microbiome of the gut, oral cavity, respiratory tract, skin, and urogenital tract was affected by factors such as geography, ethnicity, and lifestyle. 

Exploring the mysteries of the human microbiome
The Human Microbiome Project was set up to improve understanding of the microbiota involved in human health and disease.

Although the exact reasons for the variations are not understood, genetics seem to play a large role. The Human Microbiome Project (HMP) was largely dedicated to understanding this relationship. 

Established in 2007, the role of the HMP was to understand the variation in the human microbiome due to different factors, including an individual's genes, immune system, health condition, lifestyle, diet, environment, and temporary microorganism populations.

One of the key achievements of this project was the creation of a reference database on the boundaries of normal microbial variation in human beings. This has important implications for understanding the role of the microbiome in health and diseases.

The human microbiome and disease

The human body releases antimicrobial peptides, immunoglobulin A, and mucus, among other substances, which play a role in promoting the growth of certain bacteria and inhibiting others, shaping the microbiota in response to changing conditions.

Exploring the mysteries of the human microbiome
Microbiota dysbiosis contributes to various diseases.

While microbiota can help maintain the overall health of the human body, factors discussed previously can cause an imbalance, also known as dysbiosis. This can contribute to several serious diseases.

The development of cardiovascular disease, cancer, Crohn's disease, diabetes, IBD, respiratory disease, brain disorders, chronic renal diseases, and liver diseases have all now been linked to changes in microbiota.

Research has identified significant pathogens associated with these diseases and the related signaling pathways involved. This implies that specific pathogens activate specific pathways that cause inflammation and other disease-related processes, contributing to the development of particular illnesses. 

Understanding these associations can provide insights into the mechanisms underlying these diseases and potentially guide the development of targeted treatments or interventions.

Exploring the mysteries of the human microbiome
Biofilm of three species of bacterium on a colon tumour.

Maintaining a healthy microbiome

Maintaining a healthy microbiome can help boost overall physical and mental health, and there are even ways we can help this process along.

Prebiotics are a class of nutrients that have recently gained interest due to their supposed impact on our health, although this has not been proven. The theory is that they can serve as a food source for the beneficial bacteria in our gut. Then, when these bacteria break down prebiotics, it leads to the production of short-chain fatty acids that can affect other organs via the bloodstream.

Small amounts of some prebiotics, such as galacto-oligosaccharides and fructo-oligosaccharides, are naturally found in various foods. However, scientists are exploring ways to produce them on a larger scale. They may also offer potential health benefits, especially when combined with probiotics

Probiotics are live microorganisms that are meant to provide health benefits when ingested or applied topically. They are naturally found in fermented food such as yogurt, as well as in dietary supplements and some cosmetic products, such as those for the treatment of certain inflammatory skin diseases like acne and rosacea.

These bacteria are similar to the ones living in our bodies and perform several helpful functions, such as aiding digestion, destroying disease-causing cells, or producing vitamins. Although the effectiveness of probiotic supplements has not been proven, the idea is to boost the colonies of 'good' bacteria in order to maximize benefits and maintain a healthy balance of microbiota. 

Exploring the mysteries of the human microbiome
Different strategies to modify gut microbiota for disease treatment.

The most common probiotic bacteria belong to groups called Lactobacillus and Bifidobacterium

Much of the research into the microbiome has been focused on the gut, due to the large numbers of microbes involved and their effect on health. One of the newer methods developed to boost gut microbiota is fecal microbiota transplantation or FMT. This involves the transfer of fecal material from a healthy donor to an individual with a disrupted or imbalanced microbiota. This procedure aims to restore a more balanced microbial composition.

Early research suggests that FMT may be helpful for a variety of diseases, such as obesity, inflammatory bowel disease, metabolic syndrome, and functional gastrointestinal disorders.

Apart from FMT, scientists are also using engineered gut bacteria to treat diseases such as diabetes, colitis, and other pathogenic infections. This technique is also being used to create smart probiotics, which may have better efficacy than natural probiotics.

Future microbiome research

Research on the human microbiota is still in the early stages, but recent studies have made significant progress. Fundamental discoveries have shed light on the transmission of essential microorganisms from mothers to infants, including during birth, through breastfeeding, and even prior to birth. In 2018, Pamela Ferretti and her team at the University of Trento found evidence supporting this transmission. 

Exploring the mysteries of the human microbiome
Breastfeeding may help transmit important microbes from mother to infant.

Their findings were further supported by studies led by Nina Kirmiz of the University of California, Davis, and Christoph A Thaiss of the Weizmann Institute of Science, which revealed that the sugars in breast milk nourish the developing microbiome of infants, influencing their immune systems.

These discoveries underscore the significance of the human microbiome in development and health. As we look to the next decade of research, it becomes crucial gain a deeper understanding of the intricacies of the human microbiome in order to develop new therapies for diseases.

To achieve these goals, a fresh approach is needed, one that embraces an ecological and evolutionary understanding of host-microbe interactions. In a Nature article, Lita Proctor, former HMP Coordinator, emphasizes the importance of moving beyond species cataloging and instead comprehending the complex interplay between microorganisms in shaping local conditions and cellular processes.

Interdisciplinary collaboration is vital for developing a new framework to study the human microbiome. Furthermore, implementing improved data standards and sharing practices is crucial for ensuring reproducibility and facilitating analysis across studies.

Fostering collaboration and establishing shared resources, such as biobanks, analytical standards, protocols, and public databases, can accelerate progress in the field.

These concerted efforts will pave the way for groundbreaking discoveries and the development of innovative therapies.

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