We are teaming with trillions of microorganismal interactions at any given time. Who we are are humans is dependent upon the ecology stability of the trillions of microbial organisms that exist within and upon us. Humans have a total of about 20,000 genes. When we consider the egentic material of our microbiome, this number jumps to over 33 million genes. And the lowest estimates show our microbial cells to equal our human cells (1:1 ratio). The more cited studies over the past 10 years say that are human cells are outnumbered 10:1 by microbial cells. With either estimation, it\u2019s obvious the contribution of our microbiome to who we are as people is not insignificant. <\/p>\n\n\n\n
Given the times we are in today, I thought it could be useful to take a step back and look at not only viruses, but the human holobiont in its entirety, meaning the collection of microorganisms living within and upon us amongst our human cells, and consider our human microcosm and it\u2019s dependence on the interaction of all of the microbes. <\/p>\n\n\n\n
In a world where we are all very cognizant of one virus in particular, and in general, the idea of becoming diseased through germs, I think a good place to start would be by consider the etymology of the word \u201cgerm\u201d. The meaning of the word germ is \u201csomething that initiates development or serves as an origin for development\u201d. Given that germ theory, which is something we have all become familiar with in the past few months, is based on the idea of small organisms, or germs, causing disease, the definition I just gave is probably not one that would come to mind for most people. However, if we go to developmental biology, \u201cthe germ\u201d is indeed a point of origin, and we can look at germ cells. These cells are the precursors to gametes, which ultimately form the egg or sperm. So, in this context, the germ cell truly is the origin of development. <\/p>\n\n\n\n
If we take this outlook and apply it to what we would typically consider germs such as bacteria, fungi, and viruses, we can also find that many of these types of cells serve as the origin of something. Particularly, in our human bodies. We tend to think of ourselves as wholly human. However, there are estimates that our microbiomes are up to 10x greater than the number of human cells we have. <\/p>\n\n\n\n
The human holobiont encompasses our human cells and the long-term symbiotic interactions of the microbes that live within and upon us. By better understanding the holobiont, we are better able to understand our human form. These interactions are not only necessary for our development but are also crucial for us to thrive as human beings. <\/p>\n\n\n\n
I think the topic of the holobiont is particularly pertinent to our situation today as we navigate the current pandemic situation. We\u2019ve spent the last five months immersed in information about the SARS CoV2 coronavirus, and I think it\u2019s important to take a step back and consider not only how viruses can actually be helpful to our human form but also consider how microbial ecology works with our bodies. <\/p>\n\n\n\n
Every known prokaryote has a 16S rRNA sequence that is a gene that is specific to that organism. Depending on the organism there is a specific pattern within this gene sequence that can be compared to a library of sequences that can help to identify the organism. Not all organisms can be identified through this technique, for a variety of reasons, so other methods have been developed. Interestingly, it\u2019s been determined that some organisms need helper strains for proper cultivation. This implies that these organisms are dependent on the presence of other organisms to grow and thrive. Throw quorum-sensing, biophoton perceptivity, and electromagnetic field interactions these cells detect the presence of one another and can interpret their environment as favorable to develop within. <\/p>\n\n\n\n
Bacteria have a particularly important role in the regulation of our overall health as they are able to convert typically pathogenic or harmful substances in to substances that actually promote health in our bodies. One example is with a group of oral bacteria that convert nitrates to nitrites. Once swallowed, nitrites are converted to nitric oxide and contribute to lowering blood pressure, improved endothelial function, and reducing the effects of platelet coagulation in the blood. <\/p>\n\n\n\n
Dysbiosis is a state in which the proportions and amounts of species within a microbiota is disturbed. In dentistry, it is now generally understood that bacteria that were once thought to be pathologic or disease-causing are found in low amounts in healthy sites within the mouth. So disease isn\u2019t the cause of something external coming in to the mouth and causing an infection, but rather it\u2019s an imbalance between naturally existing microorganisms. <\/p>\n\n\n\n
In science, we tend to have a reductionist view in order to gain understanding. The holobiont reminds us that here is a more complete or holistic perspective that we need to be taking to understand the interconnectedness of multi-organismal beings, like ourselves. The even lesser understood states than the holobionts themselves are the transitional states that lead to holobiont stability. For example the aggregation of certain microorganisms lead to conditions that then favor different organisms than were capable of thriving before the aggregation. The vast population sizes of microbial populations and short developmental\/life cycles compared to their multi-cellular hosts enable them to develop unique capabilities for development and communication. <\/p>\n\n\n\n
It\u2019s been established that immune system maturation requires mutualistic interactions between various organisms. <\/p>\n\n\n\n
It is becoming increasingly obvious that macroorganisms such as humans, are influenced by the microorganisms they host. These microorganisms contribute to the development, evolution, and ecology of the greater organism. The hologenome is a term that encompasses the host genome and the collection of microbial genomes. This is significant because the human genome has about 20,000 genes whereas the human hologenome has more than 33 million genes. A consideration when talking about the holobiont is the balance and management of the host development through multiple microorganism relatinships and what the imbalance between these relationships can do to the host. For example, it has been shown that eliminating certain bacterial colonies in Daphnia through the use of antibiotics, then inoculating germ-free Daphnia with the disturbed microbiota, severely affected the development of the germ-free host.<\/p>\n\n\n\n
The systemic effects of the microbiots is mediated by short chain fatty acids and gases such as hydrogen sulfide, ammonia, methane, hydrogen. Short chain fatty acids are formed mainly in the large intestine through the fermentation of dietary fibers. Short chain fatty acids produced in the gut have a number of roles such as modulating inflammation throughout the body, immune response, regulating appetite-suppressing hormones. Short chain fatty acid metabolites also contain butyrate, which has a role in the metabolism of fatty acids and their subsequent use for energy. Butyrate is also an important component of the protective layer of the intestinal barrier. The stability of the gut microbiome has also been linked to the variation of lipids in the blood, including variations in blood cholesterol. Certain drugs such as antibitics and proton pump inhibitors are responsible for changing the diversity of gut flora. Proton pump inhibition drug use was found to diminish the gastric barrier as oral microbiota was found in higher quantities in the gut of PPI users than non-users. <\/p>\n\n\n\n
Gut ruminococcus break down oligosaccarhides and polysaccharides to be used as substrates for butyrate-producing Eubacterium and Faecalibacterium. Butyrate has multiple effects including the production of mucin, antimicrobial peptides, and tight-junction proteins for the gut. Interruption of this protective gastric layer is seen in IBS.<\/p>\n\n\n\n
Infants usually have higher concentrations of Bifidobacterium in their gut, however, if they were born via C section, Enterobacteriacae is present more so than bifido. Some studies have shown that dysbiosis in infant bacteria colonization can lead to the development of conditions such as asthma, Type I DM, or Celiac disease. <\/p>\n\n\n\n
Stabilization of the gut microbiome has also been linked to normal neurological development. The gut microbiota interacts with the brain in a bidirectional way and has been shown to have an effect on the stress and anxiety response. Control of the gut is primarily mediated throught the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. If there is an imbalance in the gut microbiota, there is also an imbalance in the metabolites of the short chain fatty acids which in addition to preserving the gut lining, also preserve the blood-brain barrier by being metabolized in to tight-junction-enhancing proteins. <\/p>\n\n\n\n
Candidate Phyla Radiation (CPR) are very very small organisms that are smaller than traditional bacteria and are thought to be obligate symbionts due to their small size and limited range of metabolic processing (no ETC or amino acid production). <\/p>\n\n\n\n
Fungal species are also very important for immune system development and are thought to be stimulating for the development of human immunity. Candida albicans is often found in high quantities, in oral cavities with high quantities of Streptococcus mutans. These two are linked together in mouths with a lot of carious lesions, particularly in children. <\/p>\n\n\n\n
The majority of the viruses identified in the oral microbiome are bacteriophages. Phages play a particularly important role in the transfer of genetic material. One of the reasons this is so important in the oral cavity is because of the diversity of microorganisms in the mouth. There is plenty of opportunity for organisms to gain new genetic material and horizontal gene transfer is made possible with phage activity. Bacteriophages specifically use bacteria as hosts. In the mouth phages were found in higher volumes in the subgingival spaces in patients with periodontal disease versus periodontally healthy patients. <\/p>\n\n\n\n
To further use an example of imbalance between microbes in the mouth, interacting with our cells, we can talk about cavities. Cavities can be causes by the overgrowth of microorganisms commonly present in health. Specifically, Fusobacterium and Treponema in perio pockets are anaerobic whereas Neisseria and Capnocytophaga are aerobic in perio pockets. Also, in general, higher levels of the bacteria P. gingivalis has been linked to higher levels of the inflammatory biomarker, C-Reactive protein. <\/p>\n\n\n\n
About 5 years ago, I was working in the Peruvian Amazon doing dental trip, working with the local tribes throughout the jungle. And one of the ways you are greeted is with a cup of chica, which is a fermented tea. However, it is not a tea. The women of the tribe gather together and chew up yuca, a starchy root vegetable, until it becomes soft and gummy. They then spit in in a large barrel of Amazon water, which is teaming with all kinds of microbes that my Canadian gut had never met before. After sitting in the sun for several days and being able to ferment, it becomes this drinkable tea call chica. It\u2019s something that the Amazonian communities have been drinking for generations. Not only does it connect them and those who drink it to their community, but for them, it promotes their immune health. From their perspective, we humans need to live in harmony with nature, including its microorganisms.<\/p>\n\n\n\n
Given the current situation we\u2019ve all been navigating with the coronavirus pandemic, I thought it would be worth turning our attention inward to discuss what is termed the human holobiont. Now, this is a term that may be new to some of you, so I\u2019ll give you some background on it. The term itself was coined by an MIT researcher in 1991 to describe the collection of human cells and microbial cells (including the bacteria, fungi, and viruses) that live within and upon us in long-term relationships. There are actually some other categories of smaller organisms included in the definition of this term, but for simplicity, I\u2019ll use bacteria, fungi, and viruses. Now you may be asking, is it really important to understand this and why? <\/p>\n\n\n\n
Well, these non-human bacterial, fungal, and viral cells have been estimated to outnumber our human cells 10:1. So, for 1 human cell, there are 10 non-human cells that make us who we are. And when we look at the human genome, it consists of around 20,000 genes. When considering the hologenome, or the genome of all the human, bacterial, fungal, and viral cells, we are now talking about a gene set of over 33 million genes. So the contribution these organisms have towards our humanness shouldn\u2019t be overlooked, and we can almost think of our human cells as a scaffold for an immense microbial ecology that is a part of us. <\/p>\n\n\n\n
The general idea that a germ, whether it\u2019s a virus, bacteria, or fungus, causes a disease, is based on something called Germ Theory. Germ Theory was developed in the mid-1800s by Louis Pasteur. It has since dominated as the prevailing theory in science and medicine to explain many diseases and infections. However, at the time Pasteur was working on germ theory, another scientist, Antoine Bechamp, was working on a rival theory called bioterrain theory, which actually proposed that disease was caused by, among other things, an imbalance of the organisms in our body and their environment. Now, at the time, this was regarded as nonsense and Pasteur\u2019s theory really triumphed. But as science starts to better understand things like our holobiont, and the fact that we are teeming with more microorganismal cells than human cells, we are now moving towards a shift where it makes complete sense to consider all of the microrganisms in our body and their relationships when we talk about health. <\/p>\n\n\n\n
Even the term germ today elicits the idea of disease, or dirtiness or decay. However, the etymology of the word germ is \u201csomething that initiates development or the origin of something\u201d. We see this when we consider developmental biology and look at things like germ cells, that ultimately become our reproductive egg or sperm cells, and in that sense, are absolutely the origin for another human. Also, the germ cell layers of a developing embryo are three different layers that form the human body. In this context as well, the \u201cgerm\u201d initiates development. In these contexts, the term \u2018germ\u2019 is related to development rather disease. This applies to the study of the holobiont because we can start to look at microbial cells that are typically associated with disease, through a new set of eyes, and consider how their interactions actually lead to our multi-organismal development. <\/p>\n\n\n\n
This concert of cellular interactions is so intricate and finely coordinated. For the trillions of cells that make up our bodies, there are trillions of cellular interactions, processes, and communications happening at any given time. Our cells, including our microbiomes, have developed some incredibly clever ways of communicating with one another, even if they aren\u2019t in direct relationship or proximity. For example, cells communicate with one another through the release of chemicals, hormones, and proteins. They also release what are known as biophotons, or small amounts of light that can be received by cells at a far distance. And finally, they release genetic material in a process called horizontal gene transfer. This allows cells to transfer genes to one another to impart certain genetic information from one cell type to another. Now when we disturb or interfere with these ecological populations, it can have negative effects. There are studies that have been done in small animals where the bacteria populations have been altered as a result of antibiotics. The altered microbiome is then injected in germ-free animals and their development was observed to impaired compared with the rate of development. <\/p>\n\n\n\n
We\u2019re at the tip of the iceberg when it comes to understanding these interactions but we are understanding more and more how they impact our overall health. The majority of research has focused on bacteria because of their ubiquity, but there is a recognition of this and an attempt to turn the research in the direction of fungal and viral research as well. <\/p>\n\n\n\n
Gut health has been a really hot topic in the health and nutrition spaces over the last few years. And the thing that is lesser known is that the mouth is actually the first part of our guts. So when we discuss gut health or we try to achieve gut health, we really need to be aware of the role the health of our mouths play in this. Our mouths host over 700 different types of microbes, including bacteria, fungi, and viruses. Each of these 700 different types of microbes, totalling hundreds of millions in number, are present in health. <\/p>\n\n\n\n
Dental diseases, some of which are cavities, gingivitis, and periodontitis, arise from imbalances in these over 700 different types of organisms. Dysbiosis of the microbes results in acidic metabolites eating through the hardest structure in the body, tooth enamel. This enamel breakdown causes tooth decay, which leads to localized and eventually generalized microbial changes. Specifically, the bacteria Streptococcus mutans presents in an overgrowth and this has an effect on the concurrent overgrowth of Candida albicans. Once the enamel layer has been compromised, the softer underlying structures can decay more quickly. Our teeth are like their own organs, within their hard outer casing lies nerves and blood vessels and nutrient channels, each of which can be infiltrated by microorganisms. Moving beyond the teeth, the periodontium or supporting structures of the teeth can also become inflamed through a microbial imbalance. When these bone and gum tissues start to develop microbial changes, these highly vascularized tissues become an easy route for certain bacteria, fungi, and viruses to enter the bloodstream. Studies have shown bacteria generally present in periodontitis in the mouth the be found in atherosclerotic plaques in people with cardiovascular disease. <\/p>\n\n\n\n
Oral microbes also play a role in nitrate metabolism. Nitrates can be found in many different types of food now as a preservative, particularly meat, but can naturally be found in dark leafy vegetables. A collection of microbes (Pseudomonas and Veillonella) balanced within a healthy oral microbiome will convert these nitrates to nitrites, and ultimately to nitric oxide, which has a number of beneficial effects on our body overall. Nitric oxide acts as a vasodilator, decreasing blood pressure, improving the lining of our blood vessels, and preventing coagulation in the blood. <\/p>\n\n\n\n
Also, further down in the large intestine, dietary fiber is fermented by bacteria that produce butyrate (ruminococcus), which is a short-chain fatty acid. Butyrate has the ability to improve the intestinal lining by reinforcing the tight junctions between cells of the gut lining. In fact, people with IBS or CD have been found to have lower levels of these butyrate producing bacteria, which leaves their gut more susceptible to being sensitive. Butyrate also plays a role in mitochondrial function and oxidative phosphorylation, or energy generation. <\/p>\n\n\n\n
Alzheimer\u2019s Disease is a complex, multifactored chronic condition, but its development has been linked to elevated inflammatory biomarkers (such as CRP and IL-6). Periodontal disease, and especially the dysbiosis or excess colonization of the bacteria P. gingivalis, has been linked to increased inflammatory markers in the blood. This bacteria has also been found in the brain of Alzheimer\u2019s patients. This particular bacteria produces a toxic enzyme that breaks down proteins necessary for neuronal function and cause neuronal inflammation. These elevated inflammatory biomarker (CRP and IL-6), have been linked to the development of Alzheimer\u2019s Disease over a 10 year period. <\/p>\n\n\n\n
The lungs are primarily populated by microbes arising from microaspirations of the pharynx (membrane-lined cavity behind the nose and mouth connecting them to the esophagus), for this reason, in health the microbiome of the lungs are more similar to the oropharynx or the mouth than inhaled air, the nasopharynx, or the lower gastrointestinal tract. Dominant bacteria are Prevotella, Fusobacterium, and Streptococcus. The nasal microbiome contributes little to the lungs in health likely due to the low flow of nasal fluids vs salivary flow in health. <\/p>\n\n\n\n
I realize this was an overview of a complex topic. But the takeaway I hope you get from this is that we are inextricably linked to the microbial world. We need these microorganisms in a balance with our own cells to be the healthiest versions of us. <\/p>\n","protected":false},"excerpt":{"rendered":"
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