The microbiome is made up of trillions of microbes with some 500-1000 bacterial species residing in each person’s gut, not to mention all the viruses, fungi and other microbes dwelling there also.
New advances in DNA sequencing technology has enabled scientists to start pinpointing the main players in the gut and, while informative, its application in helping to distinguish healthy gut microbes from unhealthy ones is limited due to the broad differences in the microbiomes of healthy people.
A number of factors play a role in these differences including race, sex, environment, diet and genetics. It’s the complex interplay between these variables as well as the numerous ways in which microbes interact with their host that makes knowing whether a person is healthy or at risk of disease so difficult: a seemingly small difference in the microbiomes of two people could have a profound role in health outcomes. Context is important when trying to determine what a healthy microbiome looks like.
While still in its infancy, research into what constitutes a healthy gut microbiome is providing fascinating insights, some of which will be discussed below.
Diversity
Microbes are predominantly acquired at birth, coating our skin and filling our mouths as we descend the birth canal, through the breast milk we consume and via contact with our carers’ skins during those first cuddles. It’s during the first three years of life when our microbiota is the most dynamic. Sources of bacteria now include sloppy kisses from grandma, premasticated potatoes, frolicking in the compost heap, and playtime with the pet pig. These first three years are crucial to early development in terms of immunity, metabolism and cognition. Conversely, the loss of ancestral bacteria at this age has been shown to have a deleterious effect on future health.
Whilst high microbial diversity seems to be associated with health and microbiome stability over time (5), knowing exactly which microbes constitute the ideal set for a healthy microbiome may be a moot point due to the enormous differences in the microbiomes of healthy individuals. Research is showing health as more of “a complement of metabolic and other molecular functions that are performed by the microbiome within a particular habitat but are not necessarily provided by the same organisms in different people” (6).
Resilience
Another determinant of a healthy microbiome may be its degree of resilience to external factors such as diet and drugs, and internal factors such as age. Even if your microbiome provided all the necessary functions for good health, without resilience, those functions would not last for long. So the ability to bounce back after stress and perturbation could be one of the hallmarks of a healthy microbiome (9).
The Environment
After the age of three, the microbiome is fairly stable and it’s difficult to discern between the gut of a toddler and that of an adult. That being said, changes in the gut microbiome of adults do occur, much of which can be attributed to the environments we live in, the medications we take and the diets we consume.
Studies (2) have shown differences in the microbiomes of urban dwellers living a modern lifestyle and indigenous populations living a traditional hunter-gatherer lifestyle. A reduction in gut diversity is thought to be attributed to these differences, and it’s the lack of fibre in the diet which could be to blame. The Hadza, an indigenous population in Tanzania, eat ten times as much fibre as the typical person living in western society. As a result, a certain type of fibre-digesting bacteria is significantly less abundant in urban dwellers than in those living in Hadza. Fibre is food for our gut microbes, so eating less fibre is effectively starving our microbes which leads to a reduction in diversity and, potentially, negative effects on health.
It should also be pointed out that the assumption that the western microbiome of a healthy person is a healthy microbiome is questionable. A 2018 study (7) found that migration from a non-Western country to the US is associated with immediate loss of gut microbiome diversity and function, accompanied by an increased risk of obesity.
Aside from diet, other environmental factors influencing gut microbiota composition include exposure to pathogens, stress, antibiotic use, smoking, alcohol consumption and physical activity. Fortunately these are all factors which we can control, and it would behoove us to consider our environment when assessing the health of our microbiome.
Effective Communication with Host
Over time humans and microbes have coevolved, an ancient symbiotic partnership where bacteria and animals have learnt to converse. They provide signals to us and we, in turn, signal back. It’s a vigorous and resilient setup allowing bacteria to interact with us by modulating our metabolism and immune system (1). However, it’s increasingly thought that modern life could be affecting this intricate relationship between microbes and humans.
Over the last 10,000 years the human body has adapted quickly to the rapid lifestyle changes brought on by industrialisation. Evidence shows that the microbiome has quickly adapted in response to the evolution of lactose tolerance and digestion of high-starch diets (3).
Whilst the microbiome’s ability to adapt rapidly to changes in lifestyle is commendable, it also comes with a word of caution. Modern interventions such as antibiotics and sanitisation, vital to controlling infectious disease, also have the ability to affect the healthy relationship between microbes and their host. The ‘disappearing microbiota’ hypothesis (4) suggests that ecological changes over the past 100 or so years have contributed to a shift in the types of organisms now found in the gut with a knock-on effect on disease risk.
In a perturbed microbiota – as occurs through antibiotic use – the signals from the microbes to body cells are abnormal. This can impact childhood development, leading to negative long-term physiology outcomes such as inflammatory bowel disease (IBD) , irritable bowel syndrome (IBS), obesity and type 2 diabetes (8). Thus a healthy microbiome appears to be one that can communicate clearly, one that can work in union with its host to promote health.
Limitations
While researchers have been able to improve their understanding of what a healthy gut microbiome looks like, the complete picture is still out of reach. A perfectly fine looking microbiome might be doing things that aren’t healthy, and pinpointing which components – gut composition, gene expression, metabolites, diet, etc. – are vital to a thriving gut, may well be something easier said than done.
One of the main issues affecting researchers today is a lack of data sets allowing them to draw statistically sound conclusions about the connection between the microbiome and health and disease. When increased numbers of microbiomes are sequenced, more insight will ensue.
Another issue is the locations in which studies are conducted. At present most studies are from the US, Europe and China, with little data coming from other parts of the world. In order to better understand loss of gut diversity in the industrialised world, more data is required from the guts of non-western countries for comparison. It would also allow scientists to better understand what a ‘normal’ healthy gut looks like, making it easier to observe shifts in the types of organisms found in the gut which could contribute to a knock-on effect on disease risk.
Studies conducted over many years which assess the microbiome composition as a factor contributing to health conditions are paramount for establishing causality – if microbial changes occur before a clinical change, such a conclusion could be derived. Armed with this knowledge, scientists could learn more about how the microbiome is linked to chronic conditions and physicians may be able to apply more tailored treatment.
Conclusion
A healthy gut, it appears, is not only defined by its host, but the environment to which it is subjected. Age, genetics, and diet are just some of the factors driving normal variation, information which may be used for tailored therapies.
While certain “main player” components (e.g. Bacteroidetes and Firmicutes) are consistently found in healthy adults, the relative proportions and species present vary wildly between individuals. Although researchers are starting to learn what conditions promote the health of desired species as well as recognise signs of bacterial ‘weeds’, knowledge of which strategies work best for rebalancing the microbiome and determining the optimal strategy based on the individual, is still in its early days.
Though the complete picture of what it means to be in ‘good gut health’ remains unclear, research has shown there are a number of generalised strategies we can adopt today in order to protect the beneficial microbes living inside of us and thus, increase our chances of optimal health in the future.
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References
(1) Wu, Hsin-Jung, and Eric Wu. “The role of gut microbiota in immune homeostasis and autoimmunity.” Gut Microbes, vol 3(1), 01/01/2012, 2012, pp. 4-14. NCBI, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337124/.
(2) Schnorr, S., Candela, M., Rampelli, S. et al. Gut microbiome of the Hadza hunter-gatherers. Nat Commun 5, 3654 (2014). https://doi.org/10.1038/ncomms4654
(3) Eisenstein, Michael. The hunt for a healthy microbiome. Nature, 2020, https://www.nature.com/articles/d41586-020-00193-3.
(4) Blaser, Martin J. Missing Microbes. HarperCollins Publishers, 2014.
(5) Michael I McBurney, Cindy Davis, Claire M Fraser, Barbara O Schneeman, Curtis Huttenhower, Kristin Verbeke, Jens Walter, Marie E Latulippe, Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions, The Journal of Nutrition, Volume 149, Issue 11, November 2019, Pages 1882–1895, https://doi.org/10.1093/jn/nxz154
(6) Lloyd-Price, Jason et al. “The healthy human microbiome.” Genome medicine vol. 8,1 51. 27 Apr. 2016, doi:10.1186/s13073-016-0307-y
(7) Vangay, Pajau et al. “US Immigration Westernizes the Human Gut Microbiome.” Cell vol. 175,4 (2018): 962-972.e10. doi:10.1016/j.cell.2018.10.029
(8) Langdon, A., Crook, N. & Dantas, G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med 8, 39 (2016). https://doi.org/10.1186/s13073-016-0294-z
(9) Dogra, Shaillay Kumar et al. “Gut Microbiota Resilience: Definition, Link to Health and Strategies for Intervention.” Frontiers in microbiology vol. 11 572921. 15 Sep. 2020, doi:10.3389/fmicb.2020.572921
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