Since my last post was about the negative aspects of having bacteria in your body, it seems fitting to talk about the opposite. The microbiome is the umbrella term for all the bacteria, viruses, fungi, and other microbes that live on or inside the human body. These microbes can have neutral or even positive effects on one’s health and the closer these microbes have been researched, the more complex the interactions between them and our bodies appear to be. So let’s take a very brief overview of this emerging field.
Bacteria in your Body
Bacteria represent the most diverse domain of life on Earth, making up three-quarters of all unique species. This diversity, their relative simplicity, and ability to adapt quickly means that almost any environment on Earth has bacterial species capable of thriving there, from soil to deep ocean to boiling hot springs. The vast majority of bacteria can’t survive inside the human body. Only those with specific genes can survive the precise environments (temperature, salinity, pH, etc) of the human body. But the human body collects, concentrates, and creates many useful resources like sugars and proteins, so there is an incentive for bacteria to make these adaptations. The bacteria that cause infection do so by trying to strip mine the body; they enter, they glut themselves to rapidly reproduce, then crowd out healthy tissue, release toxic waste products, and alter the environment to suit their needs better, and then they try to get as many of their daughters off to another host before the current host dies or its immune system kills them. This is certainly a strategy to survive, but it's arguably not the best one. Another strategy is to live more sustainably; deliberately not causing harm to the body so one can continue living there indefinitely. Up to 500 species of bacteria have strains capable of living inside the body without harming it. At any given time, there are ten times as many bacteria in your body as human cells, though being far smaller they only account for 3% of a person’s body mass. While some of these bacteria live in the mouth, lungs, uterus and vaginal canal, and on the skin, the vast majority of the body’s microbiome is located in the gastrointestinal tract.
The body’s first exposure to bacteria occurs during birth, as the womb is sterile but the birth canal is full of useful bacteria. Because of this, children born via Cesarean-section have a higher rate of certain autoimmune diseases (being able to kill Macbeth comes with drawbacks). During the first few years of life, babies downregulate certain parts of the immune system in order to cultivate their microbiome, using antibodies from breast milk to keep harmful pathogens at bay. The microbiome changes over the course of one’s life as new bacteria are introduced and old strains compete with each other or are affected by outside forces. Diet, medication, environmental conditions, and genetics all influence what microbes survive and thrive in one’s body, though research is still being done on how these factors influence the microbiome and how strongly they do so.
While these bacteria get to live in a safe environment where nutrients are always plentiful, our bodies have adapted to their presence and found mutual benefits. Bacteria secrete enzymes that break down complex molecules into sugars, fats, and proteins simple enough to be used, both by the bacteria and by our bodies. The enzymes produced by our gut microbiota significantly aid the digestion of dietary fiber, lactose, certain fats and proteins, and produce vitamins B7, B9, B12, and K which the body does not produce itself. Lab mice without gut microflora were found to require 30% more calories just to maintain their weight than those with healthy microflora. Another role of the microbiome, both in the GI tract and elsewhere, is preventing bacterial infection. To establish a foothold in the body and cause infection, any disease-causing bacteria has to compete against several species of microflora who are all well-established with several times the population. The microflora secrete compounds that kill or inhibit their competitors while consuming all available nutrients to leave none for the invaders. Some microflora strains have even evolved to secrete cytokines, messenger proteins used by our immune system to draw the attention of immune cells if a new competitor is particularly aggressive. Speaking of the immune system, the presence of non-deadly microbes plays an important role in the immune system’s regulation, producing cytokines to quiet an immune response once it’s no longer needed and training immune cells to be selective about what they attack.
You may be wondering, “why doesn’t the immune system just attack the microflora if they’re trained to kill bacteria?” Because the digestive tract is such an effective way for bacteria to enter the body, about 70% of the immune system’s mass is located in the intestines, so keeping the peace between the microflora and immune system is critical. The immune system in the intestines is organized into the Gut-associated Lymphoid Tissue (GALT), a collection of lymph nodes and associated tissue along the inner-lining of the intestines. While immune cells usually aren’t allowed inside the intestines proper, these lymph nodes can absorb passing molecules from the GI tract and immune cells can take samples of passing bacteria through the lymph node’s wall. In the vast majority of circumstances, these samples are used to train T-reg cells, immune cells that counterintuitively protect very specific antigens by secreting down-regulatory molecules in their presence. It’s only when damage to the intestinal wall is detected that the immune system goes on the offensive, training immune cells to attack the invaders while the existing T-reg cells protect the native microflora. Once the invader is clear, the microflora use protein signals to help to bring the immune response back down to normal and the GI tract repairs any tissue damage. In short, the immune system in the GI tract responds more closely to tissue damage than it does to bacteria, which is true for the immune system throughout the body but is especially true here. Here’s a video by Nature Video that goes into more detail.
Microflora and Health
Now that we’ve set up what our gut microbiota is and what it does, let’s talk about how it impacts our health. I briefly mentioned how the microbiota helps to regulate immune responses, and the mechanism I described above is a part of that. The GALT, along with mucus membranes in the lungs and throat, allows the immune system to be in regular contact with foreign antigens that don’t pose a threat to the body. This contact and the resulting formation of T-reg cells plays a critical role in the development of the immune system and its ability to differentiate between threatening and benign. I’ve already mentioned how Cesarean births have a higher risk* for developing allergies and autoimmune diseases later in life due to having a less robust microbiome. You may have heard some version of the Hygiene Hypothesis, which states that modern industrial societies have higher rates of allergies and autoimmune diseases because improved hygiene limits exposure to the microbes in early life that play such a critical role to the immune system’s development.
This is a tangent, but I should mention that the Hygiene Hypothesis has its critics** and the original version of the hypothesis has fallen out of favor among scientists in recent decades. The hypothesis was developed in the eighties and our understanding of the immune system has expanded significantly since then. The original hypothesis stated that it was specifically the number of infections in early childhood that improved one’s health, which has been largely disproven. A more common variation of this idea today is the Old Friends Hypothesis, which states that it isn’t the number of microbes one is exposed to that helps develop the immune system, but the exposure to very specific species of microbes that co-evolved with humans to signal directly with the immune system. These Old Friends are particularly well-suited to be gut microflora and its being exposed to them that matters more than the number of infections one has in early childhood. The role the microbiome plays in immune health is still being studied and will be for a while, but rest assured that you should still wash your hands and get your children vaccinated and treated for illnesses.
But you're probably most familiar with the microbiome as it relates to diet and digestive health. The Gut-Brain Axis is the term for the communication link between the GI tract and the central nervous system. The GBA centers on the vagus nerve, a major nerve that links most of one’s internal organs directly to the brain. Branches of this nerve connect to the intestines to receive sensory information. Many microflora species, many of them being the Old Friends referenced above, have adapted to communicate with these nerves, secreting signal molecules that interact directly with the vagus nerve. This allows the microflora to directly communicate with and influence the brain. The reverse is true as well; signals from the vagus nerve release signal molecules into the intestines that influence the microflora, causing sped up or slowed down reproduction. This is part of why anxiety can cause digestive issues, and part of why digestive issues can manifest as anxiety. This is why our diet can be so habit forming; what foods and nutrients we eat impact what bacterial species thrive in our GI tract, which then send signals to the brain to demand more of their preferred nutrients. On top of affecting diet, microflora secretions also influence insulin sensitivity and other hormones, making microflora an area of research for those studying obesity and diabetes.
The list of diseases with links to the microbiome and its dysregulation is far longer than one would suspect. Irritable Bowel Syndrome and gastric ulcers are pretty obvious diseases associated with the gut microbiome, as are many autoimmune diseases for reasons given above. But several mental health and neurological problems could also be linked to the microbiome, such as anxiety, depression, autism spectrum disorder, and Parkinson’s disease. Of the body’s serotonin (a major neurotransmitter with links to the conditions above), 95% is produced by gut microflora to communicate with the vagus nerve, so changes to the microbiome can affect the brain’s supply of serotonin. Gut microflora can release inflammatory or anti-inflammatory agents in order to direct the immune system, which when applied improperly can cause inflammation-associated diseases, including everything listed above as well as certain types of cancer. And this is only counting the gut microbiome; the diverse population of skin and mouth bacteria can change one’s susceptibility to acne and tooth decay by competing against the microbes that cause these conditions. Now, none of this is to say that the microbiome is solely responsible for these conditions; the body is extremely complicated and all the illnesses listed above have several factors influencing them. Anyone who tries to tell you that you can cure depression with yogurt alone is someone you should be wary of. But the link between these conditions and the microbiome is a fascinating area of research that will yield greater understanding of these conditions and new avenues toward treating them.
Microbiome Related Treatments
Therapeutics aimed at the microbiome are another prominent area of research with incredible potential. The microbiome can be thrown out of equilibrium by poor diet or excessive stress, but it can be severely damaged or depleted by broad-spectrum antibiotics or chemotherapy. Patients who’ve suffered such severe damage to their microbiome can suffer from chronic issues such as those we’ve discussed, but can also have their microbiome restored via fecal microbial transplantation. A person’s feces carry microbes from their microbiome and introducing microbes from a donor’s stool can be used to treat illnesses associated with the microbiome. Stool transplant has been used very effectively to treat severe C. diff infection and for experimental treatments for colitis, IBS, multiple sclerosis, and Parkinson’s disease. Studies are still ongoing as to its effectiveness against these conditions and other microbiome-associated diseases, and this methodology is still so new that there is not yet any standard methodology for administering this treatment, but its effectiveness when it works is incredibly promising. (Before you ask, either through a nose tube, enema, or colonoscopy) Other therapies associated with the microbiome include vaginal seeding, where the health risks associated with Cesarean births are mitigated by taking swabs of the mother’s vaginal fluid and wiping them on the skin, eyes, and mouth of the infant. This technique was developed in 2015 and aims to prevent long-term health problems, so research into its effectiveness is currently very limited, but it shows promise. And of course there is the gene sequencing of bacteria in a patient’s stool to identify health risks and underlying problems. The incredible genetic diversity of humanity’s collective microbiome makes figuring out what conditions are associated with which bacteria an ongoing challenge, but as medicine becomes more and more data-driven, this will be a plentiful source of useful biodata.
This is a very high-level look at a brand new field of medicine, so I have barely scratched the surface. Research is still ongoing and will be so for a while, but what we already know tells us a lot about how our bodies co-evolved and interacts with microbes. This has shifted how we think about how our bodies work and how it interacts with the world. Our bodies are not entirely our own.
For More Details
*How much higher this risk is is still being researched. Earlier studies have suggested Cesarean births could be twice as likely to develop asthma or food allergies later in life, but there are several recent studies that suggest this risk could be far lower or even negligible. Determining risk in these circumstances is tricky because one has to confirm there were no differences in how an infant was born besides vaginal or cesarean birth, which requires finding study volunteers as newborns and tracking their health for decades. The current scientific consensus is that Cesarean births are at a somewhat higher risk for certain diseases, but exact numbers are still being refined.
**As a scientist and a presenter, it is important to disclose any biases or conflicts of interest that one might have that would color one’s presentation of information. As a former ‘indoorsy’ child who has had some version of this hypothesis used to tell me to go play outside, where the bugs and humidity were, I despise the Hygiene Hypothesis for reasons entirely unrelated to its accuracy or usefulness as a hypothesis. I have done my best to keep my presentation of this information neutral and as usual I have linked to other resources which could give someone else’s perspective.
Kommentare