The human body carries tens of trillions of microorganisms every day, and that collection of microbes is referred to as the microbiome, or normal microbiota, which colonize the body but do not cause disease (usually). The microbiome is actually vital for the health and normal functioning of the human body. It includes a large variety of organisms, including eukaryotes, bacteria, archaea, and viruses. These microbes can help the body with a large range of processes, including vitamin production, digestion, immune system preparation, and defense against other foreign microbes.
In 2008, the NIH established the Human Microbiome Project (HMP), in order to comprehensively characterize the human microbiome and analyze its effects on human health and disease. This has involved a shift away from the traditional methods of microbiology, where individual microbes are isolated and studied in a laboratory environment. Traditional methods were limiting because there are many organisms that are dependent on a specific microenvironment that cannot be replicated in a lab. Newer methods include metagenomics, which is an analysis of all the microbial genomes taken in a sample from the environment. This is useful especially when used in comparison to known genomes from isolated strains, and can help establish the true complexity of microbial communities. Metagenomics has only recently been made possible by improvements in the efficiency and cost of genetic sequencing.
The first phase of the HMP, from 2007 to 2012, was intended to survey the microbial communities from the five major environments in the body (skin, mouth, nose, GI tract, urogenital tract). This was going to help determine if there is a “standard” microbial community that indicates a healthy or unhealthy host. Some studies found that people with certain GI, oral, or urogenital diseases had differences in “specific microorganisms and/or specific microbial metabolic pathways” from healthy controls. However, it was clear that a deeper understanding beyond microbial composition was generally needed to evaluate the relationship between microbial makeup and human health. The second phase of the program (2013-2016), aka the integrative HMP (iHMP), was designed to “create an integrated dataset of the biological properties of both the microbiome and host over time, in a series of disease cohorts, as a resource for the broader research community.” In other words, make a collective database of the properties of microbiomes and their hosts over time by observing groups of people who share some defining characteristic (such as pregnancy or IBS).
The gut microbiome makes up a large percentage of the total human microbial population, and plays a critical role in digestion. The metabolism of food by gut microbes often provides us with nutrients and metabolites that we cannot produce ourselves or could not make sufficient amounts of on our own. Microbial metabolism also often effects other parts of the body in ways not understood before, such as the “gut-brain” or “gut-heart” axes. The “gut-brain” association has been supported by many studies showing that gut microbiota can have an effect on the development of behavioral disorders or neurodegenerative disorders. For example, molecules produced/consumed by gut microbes can include, or affect the host production of, neurotransmitters like GABA, serotonin, or dopamine, which can all have an effect on neurological processes.
Studies have also found that the standard “Western” diet, which has a lower fiber content and fiber diversity, is associated with lower gut microbial diversity. In turn, low microbial diversity in the gut is associated with diseases like obesity, inflammatory bowel disease, cancer, and some autoimmune disorders. Cancer has been associated with specific bacteria, including Helicobacter pylori, Bacteroides fragilis, and Fusobacterium nucleatum. Some microbes like these can “produce DNA-damaging toxins and carcinogenic metabolites, induce cancer-promoting inflammation, make tumors more resistant…,” and all of these things make cancer more likely, or more deadly.
The evolution of how we view microbes in relation to our own health is interesting. At first, all microbes seem like a bad thing that we wouldn’t want colonizing our bodies, because they are “germs.” But now we know that a healthy microbiome is essential to the normal functioning of our bodies, and if the homeostasis of the microbiota is thrown off, we can be vulnerable to all kinds of diseases and disorders. The healthy microbes are part of what holds the pathogenic microbes at bay, and sometimes the “good” microbes can become pathogenic if the system is imbalanced. The human microbiome is far more complex than I ever imagined it would be. It seems that the more we learn about the little critters that live in our bodies, the more complicated it gets. We have been able to find “associations” between so many things, but we still have a lot of progress to make to use this information for treatments.
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