The human microbiome: what you need to know about how it interacts with us

The human body, including the gastrointestinal tract and other body sites such as skin, inhabits a diverse ecosystem of microorganisms, collectively known as the microbiota. There is still a lot to learn about it but we know that it plays a crucial role in human health. The constantly growing microbiome research and findings are very impressive. In prepration to write this blog, I was literally overwhelmed as to which microbiome related topic should I chose to write about because the microbiome studies are so extensive. 

Fast reading:

1. What you need to know about human microbiome?
2. Will microbiome analysis provide clear answers to your health problems?
3. How our microbiome interacts with us?
   • Human microbiome - barrier level
   • Human microbiome - immune system modulation level
   • Human microbiome - growth inhibition of harmful organisms aka colonization resistance level
   • Human microbiome - development level

What you need to know about human microbiome?

For instance, we can investigate various microbiome niches in our body, such as our gut microbiota, the mouth microbiota, the skin microbiota, the lungs or the vaginal microbiota. We can look at the microbiota globally and we can look into specific species of bacteria (bacteriota/bacteriome), into groups of bacteria and even go beyond that, by looking at the mycobiota/mycobiome (yeast, fungus), virome (viruses), and parasites residing in our guts. Then, we have different “stages” of the microbiota development staring with the infancy microbiota, the adulthood microbiota, and ending with the elderlyhood microbiota profile. We can explore the microbiota by looking at its composition, diversity, homeostatis (balance) or a degree of dysbiosis (imbalance). We have the good microbes, the “neutral” ones and the bad ones; and at the end it’s all about balance. We can look at the genetic profiles of microbes (microbiome genomes), at their metabolites (microbial products refering to microbiome metabolome); we can investigate the function of these metabolites and look at the effect of these metabolites on human physiology; and we can look at how microbial genes are regulated (switched on and switched off). On the top of it, we can study the microbiome’s role in various diseases, we can investigate the effects of medications, various dietary regimens and lifestyles on the microbiome’s fintess.

Sounds complex, right? And it is. 

Will microbiome analysis provide clear answers to your health problems?

If someone is telling you that they can - based on the list of fecal microbes – fix your gut health and your overall health, they probably do not comprehend the microbiome complexity and its interactions. It does not mean you should not do a fecal test to learn about your microbial-self. The fecal microbiome analysis can be insightful but because the gut microbiome research became such a hot topic, people get easily traped in an idea that the microbiome analysis will provide clear answers to their health problems and it’s not that simple. 

The complexity of the microbiome ecosystem itself and how it communicates with our body, makes it clinicaly exciting. Nevertheless, it is still challenging to properly understand all these interactions and to put our understanding into practice and into therapeutic intervantions. 

If you are confused with the microbiome terminology (microbiome, microbiota, microbes etc), do check the basic gut glossary here.  

Now, let’s dive a bit into how the human microbiota interacts with us. 

How our microbiome interacts with us

Main interactions with the human microbiota happen at four levels, inluding: 

Human microbiome - barrier level

We have physical barriers and chemical barriers, which selectively separate the gut microbiota and our immune system and ensure that contents within the intestine are contained. The best-studied interface for host-microbiota interactions is the intestinal mucosa and a layer of epithelial cells that separates the intestinal lumen from underlying tissues. A dense mucus layer separates the intestinal epithelium from resident intestinal microbes. These barriers prevent the leakage of microbial organisms or their products into the underlying tissues, which could inappropriately stimulate our immune system and lead to inflammation.The microbes residing along our mucosal lining (in our GI tract, reproductive tract, or our respiratory system) make products (metabolites) that help keeping the epithelial cells intact, that stimulate mucus production, and that promote wound healing. 

Human microbiome - immune system modulation level

The microbiota plays a key role in the training and the development of our innate and adaptive immune system, while the immune system governs the maintenance of human-microbe homeostatis (balance). 

The members of the gut microbiota make various molecules that can modulate our immune responses by regulating the production of immunological mediators, such as cytokines and chemokines, secreted from intestinal epithelial cells. It supports either tolerant immune pathways or inflammatory pathways. The microbial immune modulation takes place locally at the sites where the microbes reside, such as the gut, mouth, skin, vagina, and lungs, and it has systemic effects on the brain, lymph nodes, and various organs. The intestinal immune system constantly performs surveillance towards the gut microorganisms to create adequate responses and the microbiota and the innate immunity engage in an extensive bidirectional communication, a sort of crosstalk. 

Human microbiome - growth inhibition of harmful organisms aka colonization resistance level

Colonization resistance refers to resistance against colonization (overgrowth) of harmful organisms that could cause imbalance, infection, inflammation and disease. Our gut and other microbiome sites are home for various types of microbes, the good ones, the bad ones and the opportunistic ones. The beneficial ones help us resist against the colonization by the bad ones because they make certain molecules with antimicrobial effects, such as SCFAs (short chain fatty acids), secondary bile acids and bacteriocins. These compounds are vital in inhibiting the growth of pathogens and opportunistic pathogenes. Perturbations to the microbiota, such as antibiotic treatments, can alter microbial composition (lead to dysbiosis) and can result in the (temporal) loss of colonization resistance. Consequently, we might be more susceptible to colonization (overgrowth) by pathogens which can for example be manifested as diarrhea. 

Human microbiome - development level

The microbiota mode of action goes beyond the gut and the tissues the microbes reside at, the effects can be extrapolated to extraintestinal organs. Microbiome members can impact the development and function of cells within various tissues thanks to the activity of their products. The effects relate to the immune system and immune cells as mentioned above but they can also influence the physiology of other organs such as brain, pancrease, liver, and endocrine organs. Moreover, the activity of microbes can influence the bone mass and skeletal function; and the development of a healthy brain depends also (apart from other prenatal and postnatal factors) on molecular signals generated in the gut by the gut microbiota. 

Microbial molecules as the messengers that influence our physiology 

As you may have noticed, I refer here often to the effect of molecules produced by microbes and not so much to the types of microbes themselves. The reason why I do it is because it’s not only about the microbes themselves but about the products (aka metabolites, compunds, molecules) they make. It’s these “products” that powerfully influence our physiology. Gaining a better understanding in this area will keep scientists busy for years. 

A reference list: 

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3. The intestinal microbiota: Antibiotics, colonization resistance, and enteric pathogens. Kim S, Covington A, Pamer EG. Immunol Rev. 2017;279(1):90-105. 
4. Commensal Gut Microbiota Immunomodulatory Actions in Bone Marrow and Liver have Catabolic Effects on Skeletal Homeostasis in Health. Novince CM, Whittow CR, Aartun JD, et al. Sci Rep. 2017;7(1):5747. 
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12. Links Between the Microbiome and Bone. Hernandez CJ, Guss JD, Luna M, Goldring SR. J Bone Miner Res. 2016 Sep;31(9):1638-46. 
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