Microbiome 101

The human body contains trillions of teeming bacteria and other bugs. And that's a good thing. Everyone plays host to a thriving, invisible world of microorganisms, tiny bugs – including bacteria, viruses, archaea, fungi, and protozoa – that live in and on you.1-3
These microorganisms can be found everywhere the body interacts with the outside world – skin, nasal passages, ear canals, urogenital tract, and mouth. By far, however, most of these bugs live in and along the digestive tract. In fact, 99% of human genetic material comes from the bugs that live in the gut.4
The body's microorganisms form an entire biodiverse ecosystem, which, along with their genetic material, is called the microbiome.
Scientists are just beginning to understand that humans could not exist without these symbiotic partners. And this discovery is opening a new frontier of medical research and practice.
Some scientists view the microbiome as an organ because it controls many basic needs of the human body, including:
- Supplying essential nutrients
- Helping digest various types of carbohydrates
- Making vitamins, such as vitamin B12, vitamin K, biotin, and folate
- Keeping out pathogenic (bad) bacteria that cause disease
- Working with the immune system to fight disease-causing microorganisms, while leaving healthy bugs and cells alone4
Because the microbiome covers every surface of the body, whatever you come into contact with is filtered through it. Bugs are an essential part of who you are.
One revolution leads to another
It's no coincidence that a greater understanding of the microbiome comes on the heels of a genetic revolution in medicine. This revolution has shown that each person's genetic makeup is unique and affects his or her risk of disease, as well as responses to medications.
The sequencing and mapping of the entire human genome – an international effort that took 13 years – produced a wealth of information about the number, structure, function, and location of genes.5
Sequencing determines the order of the chemical substances that make up DNA segments.6 The human genome project also led to the development of many new technologies, such as high-throughput sequencing, which allows for billions of DNA strands to be sequenced at the same time.
New approaches to sequencing, known as next-generation sequencing, have made it faster and less costly to sequence all the genetic material in a sample (from stool for example) from any one individual.
Researchers and health-care professionals can use next-generation sequencing to identify variations in an individual’s genetic code, or genome.7
Coinciding with the genetic revolution, medical microbiologists began to adapt techniques from microbial ecology to investigate microorganisms on and in the human body.
The microbial ecologists had noticed that most microorganisms weren’t able to be cultured, meaning they didn’t multiply in the growth mediums typically used in petri dishes.
The microbial ecologists overcame this problem by using a new tool to identify organisms in the intestinal microbiome – right down to a specific strain.
This technique, called whole genome shotgun sequencing, identifies DNA from any microorganism, including bacteria, viruses, fungi, and even animal and human DNA, from a stool sample.
The technique provides an accurate map of the organisms inhabiting the human gastrointestinal tract, without the need to grow them in a culture medium.8
When medical microbiologists adapted this new technology to the human body, they discovered much greater microbial diversity than they anticipated, even in parts of the body that had been previously well-researched.6
As soon as scientists had both the new frontier of research and the tools to explore it, the microbiome revolution began to take shape.
The unique you
Sequencing the human genome was a huge accomplishment that produced immense amounts of data. But that achievement was elegant simplicity compared to the complexity of the human microbiome.
The human genome contains 19,000 genes.9 But the human microbiome contains more than one hundred times that number – as many as two million genes.3,10
What's more, the microbiome is divided into distinct environments, including the mouth, skin, lungs, urogenital tract, digestive tract, and other previously unexpected locations, such as a mother’s placenta.
These environments have their own unique populations of microorganisms that are adapted to a particular body site. The microbes that live in one environment are together referred to as a microbiota; for example, the gut microbiota.1
This complexity makes each person's microbiome unique, just as every person's genome is unique – and both influence human health. Your microbiome is a dynamic set of communities that are always interacting with your body and the environment.
A symbiotic connection
Until recently, scientists believed that a woman's uterus was sterile during pregnancy. However, by looking for DNA signatures, researchers discovered that microbes coexist with their human hosts starting early in life
Bacteria have been found in the placenta, in the amniotic fluid of premature infants, and in newborns' stool.11
How a baby is born will affect the microbiome. An infant delivered vaginally will have a microbiome that resembles the types of bugs present in the mother's gut and vaginal canal.
But if a baby is born via C-section, then the baby’s microbiome is similar to the microbiome of the mother's skin, other infants' skin, and even the skin of the nursing staff.12
From the very start of life, the microbiome and the body work together in a mutually beneficial relationship. The bugs in the gut microbiota break down food to provide the body with nutrients it couldn't otherwise absorb on its own.
For instance, the gut microbiota ferments dietary fiber to create short-chain fatty acids, a key source of energy for the cells that line the large intestine (colonocytes).
Short-chain fatty acids are associated with many aspects of human health, including feelings of satisfaction and fullness after eating, inflammation, cholesterol levels, and glucose metabolism.13
At the same time, the body's immune system is working with the microbiome to maintain a healthy balance of beneficial bacteria.
The microbiome poses an interesting problem for the body's immune system, whose job it is to recognize outside invaders as a threat.
For example, when the immune system detects harmful E. coli bacteria, it launches an attack. To be able to distinguish good bacteria from bad, the immune system and microbiome are in constant communication. These reciprocal interactions shape both the immune system and the microbiome.14
Your bugs and your health
How healthy are your bugs? The answer will provide insight into your overall health. Scientists are finding that undesirable disruptions in the microbiome, such as a decreased diversity of the bugs in the gut, are connected to a host of adverse conditions – including diabetes, obesity, depression, asthma, and rheumatoid arthritis.2,3,11
Obesity studies have shown that identical meals can produce very different metabolic responses in different individuals, and the balance of the different types of microorganisms in the gut is a contributing factor.3,15
One study has shown a link between the microbiome and obesity by switching the microbiomes between normal-weight mice and obese mice. After switching, the obese mice lost weight and the normal-weight mice gained weight!16
Trying to better understand the role of the human microbiome is driving research into new strategies that will promote health and treat difficult medical conditions.
For instance, although the dangerous bacterium Clostridium difficile (commonly called C. difficile, or C. diff) is present in many individuals, it rarely causes a problem. However, some antibiotics can throw the microbiome out of balance, which allows C. difficile to proliferate in the intestines.
While a C. difficile infection typically causes diarrhea and abdominal cramping, a severe case can lead to life-threatening inflammation and bleeding.17 These infections are difficult to treat because C. difficile can become resistant to antibiotics.
To treat severe cases, physicians have actually started to transplant the gut microbiome of a healthy person into the gut of the patient with C. difficile. Nearly 90% of these infections have been cured.15
Much more to learn
Researchers are finding a correlation between changes in the microbiome and a large number of health conditions, including malnutrition, heart disease, celiac disease, eczema, multiple sclerosis, colitis, several cancers, and autism.
Even depression, anxiety, extreme risk taking, and other behaviors are being linked to the microbiome. Other studies suggest that the flavors and foods a person craves can be influenced by the microbiome.16
Nevertheless, it is important to remember that correlation does not necessarily equal causation. Is an imbalance in the microbiome a cause or is it an effect of a disease or condition? Much of the research in this field is in its preliminary stage, and major challenges remain.
But this field of study now has the tools to account for the variability from one person to another in microbiome makeup, genetic makeup, and lifestyle, and numerous efforts are now underway to determine the exact role of the microbiome.
Scientists will continue to explore this invisible world and use the insights they discover to improve human health.
References
- Quigley E. Basic definitions and concepts: Organization of the gut microbiome. Gastroenterol Clin North Am 2017;46(1):1-8.
- Osiadchiy V, Martin C, Mayer E. The gut-brain axis and the microbiome: mechanisms and clinical implications. Clin Gastroenterol Hepatol 2019;17:322-332.
- Dinan T, Cryan J. The microbiome-gut-brain axis in health and disease. Gastroenterol Clin N Am 2017;46:77-89.
- Schneiderhan J, Master-Hunter T, Locke A. Targeting gut flora to treat and prevent disease. J Fam Pract 2016;65(1):34-38.
- The cost of sequencing a human genome. National Human Genome Research Institute. https://www.genome.gov/sequencingcosts/. [Accessed 2.25.19]
- Rodrigues-Hoffmann A, Proctor L, Surette M, et al. The microbiome: The trillions of microorganisms that maintain health and cause disease in humans and companion animals. Vet Pathol 2016;53(1):10-21.
- What are whole exome sequencing and whole genome sequencing? Genetics Home Reference. https://ghr.nlm.nih.gov/primer/testing/sequencing [Accessed 3.1.19]
- Wu G, Miller S, Chiu C. Clinical metagenomic next-generation for pathogen detection. Rev Pathol Annu 2019;14:319-338.
- Ezkurdia I, Juan D, Rodriguez J, et al. Multiple evidence strands suggest that there may be as few as 19,000 human protein-coding genes. Hum Mol Genet 2014;23(22):5866-5878.
- Marchesi J, Adams D, Fava F, et al. The gut microbiota and host health: A new clinical frontier. Gut 2016;65(2):330-339.
- Zmora N, Zeevi D, Korem T, et al. Taking it personally: Personalized utilization of the human microbiome in health and disease. Cell Host Microbe 2016;19:12-20.
- Asnicar F, Manara S, Zolfo M, et al. Studying vertical microbiome transmission from mothers to infants by strain-level metagenomics profiling. mSystems 2017;2:300164-16.
- den Besten G, van Eunen K, Groen A, et al. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013;54(9):2325-2340.
- Palm N, de Zoete M, Flavell R. Immune-microbiota interactions in health and disease. Clin Immunol 2015;159(2):122-127.
- Lynch S, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med 2016;375(24):2369-2379.
- Introduction to the human microbiome. The American Microbiome Institute. http://www.microbiomeinstitute.org/humanmicrobiome. [Accessed 2.25.19]
- Clostridium difficile-induced diarrhea. Merck Manual Professional Version. http://www.merckmanuals.com/professional/infectious-diseases/anaerobic-bacteria/clostridium-difficile-induced-diarrhea. [Accessed 2.25.19]