A beginner’s guide to the human microbiome

“I then most always saw, with great wonder, that in the said matter there were many very little living animalcules, very prettily a-moving.” — Antonie van Leeuwenhoek, 1860 ~ upon the discovery of bacteria.

 

What is your microbiome?

Your body is home to trillions of microorganisms that live on every internal and external surface of your body, including your digestive tract, mouth, nostrils, skin, urogenital tract, and even lungs1-3 This community of microorganisms and their ‘theatre of activity’ (the molecules they produce), is collectively known as your microbiome4.
As bacteria outnumber other microorganisms within your body, the term ‘microbiome’ is often used to describe the bacteria in your body. The vast majority of your bacteria reside in your gut (colon), with approximately 1,000,000,000,000 bacterial cells per ml of gut content! The mouth also has a high number of bacteria, but because the mouth is relatively small, the overall count is less than 1% of the colon. Surprisingly, the stomach has a much lower number of bacteria (only around 10,000 cells per ml), but this is due to the high acidity found in the stomach. In total, the number of bacterial cells in your entire body are estimated to equal your own cells.
The bacteria found in different parts of the body vary significantly. For example, the bacterial community found in the gut is vastly different to the bacterial community found on the skin, or in the mouth, or vagina. You can think of the bacteria throughout your body as its own little ecosystem, each ecosystem is perfectly adapted to its specific environment.
Example of microbiome (bacterial) composition at different sites on the body8 (percentages) at the phylum level. 
(Modified from: Cho et al. 2012). 

But don’t microbes make you sick?

Some do, but the vast majority don’t! One of the most common misconceptions is that all microbes or bacteria are pathogens. In fact, the vast majority of bacteria in our bodies are either beneficial or are harmless to us. The misconception that bacteria=bad perhaps began when bacteria were first identified as being the cause of many diseases. It wasn’t until scientists developed better tools to study our microorganisms, when they realised that bacteria were also found in high numbers in healthy individuals. And now scientists have even better tools which enable them to study the exact mechanisms that bacteria use to assist us with staying healthy.
 

Bacteria are the foundation of all life on earth!

In the very beginning, first there were bacteria, then came everything else. Everything that lives on this planet has evolved in the presence of bacteria. And everything on this planet, living or otherwise, has its own microbiome. You, your pet, a fly on your wall, your house plants, your kitchen benchtop, your phone screen…  Everything has a community of bacteria living on it and in it. But instead of frantically disinfecting away these communities, we need to understand that the bacteria that surround us underpin the very foundations of our survival. We need them, they don’t need us.
 

How did I get MY microbiome?

Everyone has their own unique microbiome10, shaped over a lifetime by genetic heritage and specific lifestyle factors. Just like a person’s genetic code is unique to them, so is their microbiome. Formation of the microbiome begins at birth. It is now thought that it first begins during pregnancy via the placenta and amniotic fluid11, where low levels of bacterial cells may be the very first interactions that we have with bacteria. Then, when babies travel through the vaginal canal, receive skin-to-skin contact, and begin feeding, their microbiome begins to form distinct ecosystems.10-11 It is no coincidence that the same bacteria (Lactobacillus) dominate both the mother’s vagina, breastmilk, and also a newborns gastrointestinal tract!  Over time, the microbiome continually develops and changes in a reflection of our day to day choices – the surroundings we live in, the foods we eat, the people and animals we have contact with, the medications we take, and the activities we take part in -all contribute to our microbial diversity.
 

Why is our microbiome so important?

When a microbiome is well-balanced and functional, it assists with maintaining your body in a healthy state12. This includes regulating your digestive and immune systems13-14, protecting you against germs13-14, breaking down food to release energy and produce vitamins11, as well as regulating your behaviour and emotional well-being15 through hormone secretion and regulation.
 

Up to 95% of our serotonin is manufactured in our guts with the help of key microbes!16-17

 
Mental and behavioural states can be altered by the microbiome. Many strains of gut bacteria produce and respond to the same neurochemicals that we do!, such as GABA, serotonin, norepinephrine, dopamine, acetylcholine and melatonin. GABA is crucial for keeping brain networks properly balanced and inducing relaxation and sleep; dopamine and norepinephrine help to regulate our motivation and feelings of reward; acetylcholine, affects our memory, movement and ability to concentrate; and serotonin is critical to feelings of wellbeing and calmness. Microbes can also produce or trigger the release of substances with anti-depressive properties such as short-chain fatty acids, and a recent study found that depressed people had fewer butyrate-producing bacteria.19 Conversely, some microbes can trigger the release of pro-inflammatory molecules called cytokines. Inflammatory cytokines can disrupt brain neurochemistry and make people more vulnerable to anxiety, depression and decreased cognitive function, but they are also critical responses to infection and injury.
 

An analysis of healthy people found that GABA was produced by a large number of their microbiome species, whereas in patients with depressive disorders GABA-producing bacteria were in much lower numbers18

 

Your microbiome also plays a critical role in immune health by first providing a protective barrier along the gut wall, preventing any harmful microbes and toxins from entering the blood stream, whilst simultaneously allowing vitamins and nutrients to pass through. By producing a stable ecosystem within you, your beneficial bacteria inhibit the colonisation and growth of invading pathogens, and thus protect you from sickness. Secondly, these microbes also continuously regulate your immune defences by producing molecules and chemical signals that interact and communicate with your immune cells. This back-and-forth communication between your microbiome and your immune system allows for swift and effective action against harmful pathogens, whilst also preventing your body from overreacting to harmless substances (as seen in autoimmune conditions). 
 

Almost 70% of your immune cells can be found in your gut, making it one of the largest immune organs in our body!

 
Finally, the microbes in your body also play important roles in the breakdown of molecules and nutrients into biologically ‘active’ versions that are useful to our bodies. Without bacteria performing these intermediate steps our bodies would be much less efficient at using some of these molecules. Estrogen, which is crucial for the regulation of both men and women’s reproductive health, is one such example. Vitamin D is another example of a molecule which needs to be broken down into a biologically ‘active’ form, and a recent study found that gut bacteria are closely associated with active vitamin D levels.
 

Did you know? ...Mice displaying anti-social behaviours were found to have a microbiome deficient in the bacterium Lactobacillus reuteri, and when researchers gave these mice an L. reuteri supplement, the anti-social behaviour disappeared20-21.

 

What does a healthy microbiome look like?

Despite all the information we have regarding the crucial role the microbiome plays in our health and wellbeing, characterising what a ‘healthy microbiome’ looks like is difficult. It is generally accepted that a ‘core’ microbiome must exist: a microbiome that is common to all humans and crucial to our biological functioning. However, a universal ‘core microbiome’ based purely on what species are present and the abundance of those species has yet to be charecterised.6,22 Instead, researchers are coming to the realisation that a core microbiome based upon ‘what the microbes are doing’ is more appropriate. This is known as the ‘functional core microbiome’ and instead refers to the specific jobs that certain microbes carry out. For example, different microbial species may be able to carry out the same function, therefore if one particular strain is not present, other microbes might be compensating for that function (i.e. producing the same molecules or inducing the same chemical pathways). In fact, highly variable species compositions across different individuals is often underpinned by surprisingly similar functions. 23&24
Further, ‘abundance’ does not necessarily correlate with ‘importance’, as even microbes with low abundances have been found to perform very important jobs crucial for our health. For example, human resistance to Salmonella infection is related to a rare microbe.25 Therefore, how ‘important’ a microbial species is, rests on how ‘useful and unique’ the job that it performs is. Further complicating matters, some communities of bacteria work together (synergistically) to achieve a specific function as a group24. For example, consider that a community of ten different bacterium could be working together to achieve the same functional output as another singular bacterium that can achieve the function on its own. As long as the function is achieved, the person remains healthy, it does not necessarily matter whether it is one bacterial strain or a collection of different bacterial strains performing the function.
Another reason why it is difficult to figure out what a ‘healthy microbiome’ looks like, is that not all bacteria in the human microbiome have been fully characterised. 26&27 It is estimated that 35 - 65% of bacteria have not been characterised yet18&28 (i.e. they will not grow them in a laboratory setting to allow us study them, but we know that they are there because we can detect their DNA in our gut) 26-28 Also, as people live in different environments, and have different lifestyles and food preferences, what is optimal for one person may not be optimal for the next. Despite these rather complicated unknowns, there ARE a number of specific, well-studied, bacterial strains that seem to be common to all humans  and play exceptional roles in our health.
 

When a microbiome becomes disturbed…

Occasionally, the microbiome may become disturbed or imbalanced. The beneficial bacteria that keep you healthy can die-off and become replaced with less beneficial bacteria, or worse, with pathogenic (detrimental) bacteria. Effectively, the microbiome shifts from an optimal, highly functional community, to a less optimal or even detrimental one, which then contributes to numerous health issues. This imbalance is commonly referred to, in the medical field, as microbial dysbiosis. Microbial dysbiosis can be caused by a number of factors, such as a diet lacking in plant-based fibre, lack of physical activity, poor sleep patterns, heightened stress, chronic use of medications, prolonged time spent indoors, or injury and infection. For more information on dysbiosis click here.
 

We have also compiled a step-by-step guide on how to best support your microbiome health HERE. We base these guidelines on the latest scientific research.

 

 

 

Supporting Literature:
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3Aagaard et al. (2013). The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters. FASEB J. 27, 1012–1022. doi: 10.1096/fj.12-220806
4Berg et al. (2020)Microbiome definition re-visited: old concepts and new challenges. Microbiome 8, 103. https://doi.org/10.1186/s40168-020-00875-0
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9Stone et al. (2020) Disinfectant, Soap or Probiotic Cleaning? Surface Microbiome Diversity and Biofilm Competitive Exclusion. Microorganisms. 8, 1726.
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15Lyte (2013) Microbial Endocrinology in the Microbiome-Gut-Brain Axis: How Bacterial Production and Utilization of Neurochemicals Influence Behavior. PLoS Pathog 9(11): e1003726.
16Reigstad et al. (2015) Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 29, 1395–1403.
17Yano et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161, 264–276.
18Strandwitz et al. (2019) GABA-modulating bacteria of the human gut microbiota. Nat Microbiol 4, 396–403. https://doi.org/10.1038/s41564-018-0307-3
19Valles-Colomer et al. (2019) The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol 4, 623–632. https://doi.org/10.1038/s41564-018-0337-x
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21Buffington et al. (2016). Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell 165, 1762–1775.
22Huse et al. (2012) A Core Human Microbiome as Viewed through 16S rRNA Sequence Clusters. PLoS ONE 7(6): e34242. https://doi.org/10.1371/journal.pone.0034242
23Burke et al. (2011). Bacterial community assembly based on functional genes rather than species. PNAS, 108, 14288–14293.
24Louca et al. (2018). Function and functional redundancy in microbial systems. Nature Ecology & Evolution, 2(6), 936–943.
25Velazquez et al. (2019). Endogenous Enterobacteriaceae underlie variation in susceptibility to Salmonella infection. Nature Microbiology, 4(6), 1057–1064. 
26Dick et al. (2013) Omic Approaches in Microbial Ecology: Charting the Unknown: analysis of whole-community sequence data is unveiling the diversity and function of specific microbial groups within uncultured phyla and across entire microbial ecosystems. Microbe Mag. 8:353–60.
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28Almeida et al. (2019). A new genomic blueprint of the human gut microbiota. Nature 568, 499–504. doi: 10.1038/s41586-019-0965-1