microbiome 101

The Microbiome

In the 1670s, a Dutch scientist named Antoine van Leeuwenhoek found something unexpected looking through the lens of his microscope [1]. Whenever he glanced at a sample of water, poop, or soil under his microscope he spotted what looked like wiggling creatures that he called “very little animalcules”. He was among the first to discover the community of tiny creatures living all around us and even inside our gastrointestinal tract [1],[2].

Fast forward a few centuries later. Now we know that for tens of million of years, a cornucopia of microorganisms co-evolved with mammals [3]. They’ve evolved to live on every surface of our body and even inside of our gut, with special adaptations that allow them to make use of whatever we can’t digest. 

Gut microbes help us break down foods like fibers that we wouldn’t otherwise be able to process and are also key for the development of the immune system [4],[5]. They help the body tell the difference between dangerous disease-causing microbes and helps the immune system learn not to attack itself. This is an introduction to a world inside a world – your microbiome.

What is the gut microbiome exactly?

There are trillions of microorganisms living in the gut, comprised of dozens of different species performing important metabolic functions. 

The gut microbiome refers to the collective genomes of all the microbial organisms living in that space [6]. The gut microbiota refers to the individuals themselves, rather than their genomes [6]. The microbial creatures span among multiple ancient lineages:

There are roughly as many bacterial cells inside you as there are human cells [7]. While bacteria are the most studied portion of the microbiome, scientists are working on a better understanding of the other types of microbes especially bacteriophage.

Microbiologists measure the gut microbiome in the same way that an ecologist would look at a forest, prairie, or jungle. Using an ecosystem level approach, they can look at the alpha diversity of the microbiome by counting how many of each type of microbe is present in a sample. While generally, higher levels of alpha diversity are thought to be beneficial, this rule doesn’t always hold true [8]. In fact, we don’t know what the healthy microbiome looks like because it is different for everyone.

The gut microbiome across the lifespan

It is now thought that the first microbes make their home in the gut during the birthing process. Remarkably, there are some differences between the microbiome of babies born through a Caesarean section and those delivered vaginally [9]. From there, many other factors impact what microbes make a home: antibiotic use and illness, breast milk, formula, and other environmental stressors [9]. 

The only reason babies can break down the complex sugars inside of breast milk is through the help of specialized Bifidobacteria found in the breast milk that then make a home in the infant’s gut [10]. As more foods are introduced in early childhood, the number of different microbial organisms increases. Exposure to these microbes helps the immune system mature and prevents auto-immune reactions.

By the time an infant reaches the age of two to three, the microbiome becomes relatively stable resembling what it will look like across most of adulthood. It still changes day-to-day depending on diet, exercise, sleep, prescription drugs, and many other factors. But since most adults have a consistent routine, the microbiome cycles through a range of regular configurations. This can still be altered however, if we change our diet and exercise radically, we can shift our microbiome. As we age and we become frailer, the microbiome starts to become more disorganized and destabilizes [11]. 

What are probiotics, prebiotics and synbiotics?

There are many different products that are designed for the microbiome, but the terminology can get confusing. This is your guide to understanding the definition of each and what they can and can’t do. 

Probiotics: According to the International Scientific Association for Probiotics and Prebiotics (ISAPP), these are: “Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host[12].”

This is a very specific definition that isn’t met by all the products offered on the market. For one, these microorganisms need to be live and viable even when you swallow them, and they must be dosed appropriately. While some yogurts may contain beneficial microbes, they might not meet the criteria for probiotics.

Prebiotics: Simply put, this is food for microbes. The ISAPP defines a prebiotic as “a substrate that is selectively utilized by host microorganisms conferring a health benefit [13].” This includes digestible fibers found in foods like sourdough bread that we can’t break down, but our microbes can.

Synbiotics: Think of a synbiotic as a specific formulation that consists of a probiotic and a prebiotic packaged into one capsule. ISAPP defines them as “a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host [14].”

How do we know gut microbes are important?

When scientists are trying to figure out whether a gene or protein is important for health, they remove it from the system with a scientific experiment. This might involve making a mouse model that doesn’t have a specific gene or protein. In the case of the microbiome, it means raising animals in the absence of any microbes to see what happens.

Without microbes, the animals don’t grow or develop properly – there are issues with the gut itself, the immune system in the body and the brain doesn’t mature, and the animals can’t process all their nutrients [15]. We’ve also made strides in understanding the importance of the microbiome in humans. 

With any disease or disorder, including irritable bowel syndrome, scientists have noticed that there are differences in the microbiome. But we don’t know whether these differences contribute or even cause the disease or whether it is the other way around. Additionally, many people who are sick or experience gastrointestinal symptoms will change the way they eat, contributing to this chicken-and-egg conundrum.

There are loads and loads of evidence suggesting that the microbiome is important for just about everything our body does but we’re still in the process of decoding the details. In the meantime, here is what you can do to keep your microbiome happy and healthy. 

Conclusion

Remarkably, the gut microbiome isn’t one static system – it is constantly changing in response to what you’re eating, the time of day, any medications you’re taking and because of many, many, many other factors. 

Eating a healthy Mediterranean-style diet full of vegetables, leafy greens, fruits, fish, and olive oil can help feed your microbiome. These foods contain indigestible fibers and molecules like polyphenols that are eaten and transformed by the gut bacteria into useful messengers for our body. These messages are important for healthy gut transit, digestion, and immune system function [4],[5].

Consistently eating healthy will help beneficial microbes establish their niche within the gut, keeping pathogenic organisms out, and aid in digestive health.

Key Findings from 2022

  1. The gut microbiome plays a role in the effectiveness of cancer immunotherapy
  2. A step toward understanding the role of the microbiome in aging
  3. Using viruses to knock-out specific gut microbes associated with irritable bowel disease
  4. Characterizing a new bacterial-derived molecule that alters brain activity and anxiety in mice
  5. Understanding how the microbiome affects glucose control in people with Type 1 diabetes
  6. In mice, the gut microbiome impacts food preferences – upending you are what you eat and suggesting you eat what you are
  7. We need more diversity in microbiome datasets to eliminate research biases
  8. The gut microbiome may explain why some people don’t respond as well to a class of blood pressure medications called statins
  9. Skin anatomy plays a role in determining which microbes live on it. The strains that existing between different pores on our skin can be completely different from each other.
  10. Scientists sequence and characterize hundreds of previously unknown species

References

  1. “Antonie Van Leeuwenhoek.” Encyclopædia Britannica, Encyclopædia Britannica, Inc., https://www.britannica.com/biography/Antonie-van-Leeuwenhoek. 
  2. Pariente, Nonia. “A Field Is Born.” Nature News, Nature Publishing Group, 17 June 2019, https://www.nature.com/articles/d42859-019-00006-2. 
  3. Groussin, Mathieu, Florent Mazel, and Eric J. Alm. « Co-evolution and co-speciation of host-gut bacteria systems. » Cell Host & Microbe 28.1 (2020): 12-22.
  4. Tilg, Herbert, and Alexander R. Moschen. « Food, immunity, and the microbiome. » Gastroenterology 148.6 (2015): 1107-1119.
  5. Thaiss, Christoph A., et al. « The microbiome and innate immunity. » Nature 535.7610 (2016): 65-74.
  6. Berg, Gabriele, et al. « Microbiome definition re-visited: old concepts and new challenges. » Microbiome 8.1 (2020): 1-22.
  7. Sender, Ron, Shai Fuchs, and Ron Milo. « Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. » Cell 164.3 (2016): 337-340.
  8. Cowan, Caitlin SM. “Is High Diversity Always a Good Thing?” World Microbiome Day, 16 July 2020, https://worldmicrobiomeday.com/blog/is-high-diversity-always-a-good-thing/.
  9. Codagnone, Martin G., et al. « Programming bugs: microbiota and the developmental origins of brain health and disease. » Biological psychiatry 85.2 (2019): 150-163.
  10. Fehr, Kelsey, et al. « Breastmilk feeding practices are associated with the co-occurrence of bacteria in mothers’ milk and the infant gut: the CHILD cohort study. » Cell Host & Microbe 28.2 (2020): 285-297.
  11. Hill, Colin, et al. « The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. » Nature reviews Gastroenterology & hepatology 11.8 (2014): 506-514.
  12. Wilmanski, Tomasz, et al. « Gut microbiome pattern reflects healthy ageing and predicts survival in humans. » Nature metabolism 3.2 (2021): 274-286.
  13. Gibson, Glenn R., et al. « Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. » Nature reviews Gastroenterology & hepatology 14.8 (2017): 491-502.
  14. Swanson, Kelly S., et al. « The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. » Nature Reviews Gastroenterology & Hepatology 17.11 (2020): 687-701.
  15. Spichak, Simon, et al. « Without a bug’s life: Germ-free rodents to interrogate microbiota-gut-neuroimmune interactions. » Drug Discovery Today: Disease Models 28 (2018): 79-93.