One of the burning questions about the human gut microbiome is “what is the definition of a healthy gut microbiome?”.
The first thing to know is that microbiome science is still quite young and we are still learning. Naturally, there will also be assumptions we currently have that are later proven to be incorrect. Currently, the level of publicly available gut microbiome samples is quite low compared to the number of people who have had their genome sequenced for science. This means that microbiome science is in its infancy compared to the field of genomics.
So, with that in mind, let’s take a look at our current understanding of what a healthy microbiome might look like.
- Diversity of species
- Community stability, or resilience
- Typical categories of bacteria should predominate
- Healthy levels of Short Chain Fatty Acid producing species
- Healthy presence of Keystone species and "peacekeepers"
- Reasonable levels of Proteobacteria and Sulfate Reducing Bacteria
- None or minimal levels of pathogens and pathobionts
- Conclusion - defining a healthy gut microbiome
- Want a healthy gut microbiome?
It’s important to understand that each person’s gut microbiome is unique – it’s believed that we only share around 30% of our gut microbiota with another person. Microbiota refers to the microbial community itself and microbiome refers to the collective genes of those microbes.
There are many factors that influence the makeup of an individual’s microbiome. For example, gender has also been found to be associated with key differences– for example, women have a lower level of what’s known as a keystone species called Faecalibacterium prausnitzii.
In one part of the world, the microbiome of individuals differs greatly from other parts. For example, hunter-gatherer populations in Africa that are considered healthy are mostly “lacking” a beneficial genus called Bifidobacterium that is more abundant in the West and considered essential to good health.
With these considerations in mind, following are the key things we currently believe constitute a “healthy microbiome” in broad terms. There is still much work to be done in terms of proving absolute causality in regards to all of these points when it comes to the influence of the microbiome on our health.
Diversity of species
Considered a key marker of a healthy microbiome, diversity of species is important since the microbiome is a complex ecosystem with interaction between commensal species, pathobionts, pathogens and the host (us). All of the bacterial species have their own important role to play in this ecosystem. Over time, due to numerous insults such as overuse of antibiotics, scientists have observed that many ancestral microbial species are slowly dying out over generations, reducing diversity in individuals and collectively. Some studies suggest that we’ve already lost about 50 percent of the diversity in our microbiome, which is a very sobering thought indeed.
Community stability, or resilience
Community stability or resilience is another factor considered to represent the health of an individual’s microbiome. A healthy microbiome is more resistant and resilient to disruption. Antibiotics are considered a key microbiome disruptor, with many species never returning even after a single round.
Typical categories of bacteria should predominate
The gut microbiome should predominantly feature what are known as obligate anaerobes – this means they flourish without oxygen in their environment. Bacteria that can tolerate the presence or lack of oxygen are known as facultative anaerobes. When oxygen homeostasis is disturbed, it may lead to many secondary issues including the growth of pathogenic species.
Healthy levels of Short Chain Fatty Acid producing species
Short Chain Fatty acids are metabolites produced by gut bacteria that play a key role in the health-enhancing effects of a healthy microbiome. Most fibers can’t be digested by humans, so we rely on the gut bacteria to do that for us. The fibers are fermented by the bacteria which produce special metabolites. This is why a fibre-rich diet is so important, particularly one with variety.
Butyrate is a key type of SCFA (Short Chain Fatty Acid) that has many gut-specific and body-wide physiological benefits. Low levels of butyrate have been identified in many disease states such as Type 2 diabetes mellitus and IBD. Promotion of SCFA production using certain dietary fibres and prebiotics also helps to keep levels of potentially inflammatory Proteobacteria and Sulfate Reducing Bacteria (SRB) under control (see below).
Microbial SCFAs impact on gut health, as an energy source for the intestinal epithelium and as an epigenetic factor influencing immune response, electrolyte re-absorption and gut motility. Butyrate specifically is an energy substrate used by colonocytes, while acetate and propionate reach systemic circulation and affect metabolism and function of peripheral organs (e.g. liver, pancreas, brain, muscle).
The presence of end metabolites such as the SCFAs acetate, propionate and butyrate, and absence of intermediate metabolite accumulation, such as for lactate, formate and succinate, are generally recognized as markers for a healthy microbiome.
Healthy presence of Keystone species and "peacekeepers"
The concept of “Keystone taxa” was first developed by ecologist Robert T. Paine in 1966. It’s generally agreed that different species - keystone species - have an outsized influence on overall ecological communities, playing an important role in the resilience of the community over time. Microbial communities, such as the gut microbiome, are now known to have keystone species, however the research to identify these is still in its infancy and the concept itself needs more definition.
"Peacekeeping" species - belonging to the Clostridia clusters of bacterial species - help to keep inflammation under control by supporting immune function, so that the immune system correctly identifies threats and maintains tolerance to microbes that are usually found in the gut. These species are particularly good at producing butyrate.
Reasonable levels of Proteobacteria and Sulfate Reducing Bacteria
Overgrowth of bacteria from the Proteobacteria phyla is associated with lower levels of health-promoting Firmicutes species - known for their production of butyrate -, lower levels of diversity and has also been identified in undernourished children and those with IBD. Bacteria in the Proteobacteria phyla include many opportunistic pathogens and are also known for high levels of pro-inflammatory LPS/endotoxin among the gram negative species.
Proteobacteria also produce many potentially harmful compounds such as ammonia, branched-chain fatty acids, amines, sulfur compounds, phenols, and indoles (derived from amino acids).
Proteobacteria are efficient producers of alcohol, which is believed to play a role in non-alcoholic fatty liver disease (NAFLD).
A higher abundance of Proteobacteria and a lower abundance of Bacteroidetes has been found in colorectal cancer cases compared to healthy people.
The pattern of Proteobacteria overgrowth alongside low levels of butyrate is considered a key microbial signature of gut dysbiosis, usually leading to gut inflammation. This pattern has been identified in a number of chronic conditions/states such as IBD, IBS, histamine intolerance, diverticulitis, colorectal cancer, Type 2 diabetes and obesity.
In a healthy gut, Proteobacteria species usually make up to 4.5% of the total. In some cases, the relative abundance temporarily rises to up to 45% without negative effects on the health of the individual. This is thought to be because Proteobacteria are quite sensitive to environmental changes, such as diet. So it's the long term abundance of Proteobacteria which matters most. A low fiber intake has been linked to the expansion of Proteobacteria.
Sulfate Reducing Bacteria (SRB) are a subset of Proteobacteria - they consume hydrogen and sulfate, converting these to Hydrogen sulfide (H2S). H2S is a necessary gasotransmitter known to play a role in nerve health, eye health and kidney health. But, in high amounts, it can impair the colonocytes and damage the gut mucosa, potentially leading to the development of IBD. Elevated hydrogen sulfide concentrations and increased proportions of sulfate-reducing bacteria are reported in IBD and also Type 2 diabetes mellitus. Hydrogen sulfide in excess can also cause diarrhea and overly smelly flatulence.
None or minimal levels of pathogens and pathobionts
Pathogens are defined as organisms that cause disease. The presence of one or more pathogens in the gut microbiome is indicative of an unhealthy microbiome with poor defences. In a healthy microbiome, commensal (friendly) bacteria are usually able to outcompete pathogens via various defence mechanisms.
Pathiobionts are resident microbes with pathogenic potential. Organisms proposed as pathobionts are associated with chronic inflammatory conditions, unlike opportunistic pathogens which often cause acute infections and are typically acquired from the environment or other parts of the body. In addition, pathobionts are usually harmless or even beneficial to the host (the person) under normal conditions, distinct from traditional pathogens which may cause disease even in healthy hosts.
Conclusion - defining a healthy gut microbiome
With all of this variation, it’s clear that there is not a singular well-defined healthy microbiome profile and there will never be. What’s considered a healthy microbiome for one individual is going to look quite different in another individual. This is because there is a complex interplay between so many factors influencing our health - the microbiome is just one factor in the larger context. Subtle microbiome differences between individuals may have a significant impact on health due to the various factors all coming together.
This means that it’s not yet possible to definitively define a healthy microbiome and draw statistically sound connections between the microbiome and health or disease. It’s also possible that a disturbed microbiome may be a consequence of disease rather than a cause - of course this is hotly debated but may certainly be true to an extent. While there are many associations observed between microbiome patterns and disease, we know that correlation does not equal causation - future research will need to determine causality before making definitive conclusions.
But there do certainly seem to be some broad patterns that can be identified to determine whether an individual’s gut microbiome is generally healthy or not.
I hope you found this article helpful to you on your gut health journey.
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