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What Can A Microbiome Test Tell You That A Genetic Test Can't?

Loukia Lili, PhD
Onegevity

Genetic tests have become increasingly popular and less expensive over the past decade. It only takes a small sample of blood or saliva or a few strands of hair. But your genetic test won’t answer all your questions, particularly if you’re wondering what is causing issues in your GI tract. Learn when its appropriate to do a genetics test and when you would be better off testing your gut microbiome to learn about your health. 


Current genetic tests – what can you learn from a DNA test?

A genetic test aims to identify possible unusual patterns in your genetic makeup. Your genetic makeup consists of your inherited (germline) and your differentiated (somatic) DNA, both of which are encoded and carried in the chromosomes that make up your cells and organs. Your entire DNA, both germline and somatic, reflects your health, vitality, and optimal function of every part of your body by regulating the expression of genes and proteins. A genetic test can check for changes in the chromosomes, genes, or proteins, and it can identify genetic conditions or the chance of developing or passing on a genetic disorder to your kids. 


There are many applications of genetic tests that span a variety of medical fields including preimplantation testing for possible genetic abnormalities before in vitro fertilization, newborn screening for neonatal disorders, diagnostic and carrier testing for inherited disorders from your parents, predictive and pre-symptomatic testing for adult-onset and complex disorders, and pharmacogenetic testing to guide individual drug selection, dosage, and response. And commercially, genetic testing is being used by many for personal information and educational purposes, like genetic ancestry (i.e., genealogy or family history) or wellness status (e.g., reports on disease carriers, food sensitivities, athletic potential, etc.).


Genetic tests – they are easy to do!

Genetic tests can be performed either in a clinical setting, like a hospital or doctor’s office or at home. Depending on the genetic analysis, a shorter or a longer piece of your DNA may be required, and, in the case of a test that involves whole genome sequencing, your entire DNA needs to be sequenced, read, and analyzed. 


To understand the scalability of the various genetic tests, you can consider that a single change in the sequence of your DNA involves a single change in one base, a single gene contains approximately 3,000 bases, genetic loci have 30,000 to 3 million bases, a chromosome has 100 million bases, and our entire DNA consists of 3 billion bases. 


You can also think of your DNA sequence as a book that tells your story with significant words, sentences, and paragraphs. What’s important to realize is that not every word, sentence, or paragraph is significant. Genetic tests are designed to determine what is significant and insignificant--  in a case by case example. One letter is like a base. Many letters (bases) make up a word (genes). Words (genes) are put together to make sentences (chromosomes), but the sentences (chromosomes) contain both significant and insignificant words creating your entire book, your entire story, your entire DNA. Some genetic tests read genes and loci (i.e., areas with meaningful or unmeaningful information) that involve a few specific bases, while other tests require reading and analyzing the entire human DNA story.


The data that comes from analyzing the entire human DNA is considered BIG data. 


Here are the most common options of genetic tests and what you can learn from each:


  • Molecular genetic test or gene test: This test utilizes a sample of blood, saliva, hair, skin, amniotic fluid (the fluid that surrounds a baby during pregnancy), or other tissue. The molecular genetic or gene test examines short lengths of DNA or regions of genes to identify variations or mutations (single- or many- base DNA changes) that are clinically linked to genetic disorders.1
  • Chromosomal genetic test or karyotyping: This test typically uses samples of blood, amniotic fluid, bone marrow, or other tissue, and analyzes chromosomes or longer lengths of DNA. The goal of this test is to help diagnose genetic diseases, possible congenital disabilities, and certain disorders of the blood and the lymphatic systems.2
  • Biochemical genetic test: This test studies the amount or the activity of specific enzymes or proteins. Possible unusual quantity or activity of a specific protein can indicate changes to the DNA that result in a genetic disorder. The biochemical genetic test can be performed from a blood or urine sample, spinal or amniotic fluid, or other tissue.3
  • Whole-exome and whole-genome sequencing: These two methods are increasingly used in healthcare and research to identify genetic variations, and they rely on new technologies that allow rapid sequencing of large amounts of DNA. These new technologies are known as next-generation sequencing (or next-gen sequencing). 
    • Exome sequencing involves the reading of all exons, the pieces of your DNA that provide instructions for making proteins (or all meaningful information, if you consider the example of the book), which is only about one percent of your entire genome. Because research has identified DNA variations outside the exons that affect genes and proteins and lead to genetic disorders, exome sequencing will not be sufficient to capture the DNA variations that happen outside the exons. 
    • In this case, whole-genome sequencing that reads the whole DNA genome in its entirety can determine all variations in any part of the genome, and it is the most powerful and informative genetic test.4


Microbiome tests – how are they different than genetic tests?

A microbiome test is designed to examine the community (both the quantity and composition) of commensal, symbiotic, and pathogenic microorganisms that inhabit the human body. Microbial communities in and on the human body that are being microbiome tested commonly include the digestive tract (gut), skin, mouth, nose, and vagina. In these locations, the human microbiome contains bacteria, fungi, archaea, and viruses – and their genetic components. Different from a genetic test, a microbiome test (no matter the area tested) does not measure human DNA—it measures those microorganisms!


In 2008, researchers pioneered the Human Microbiome Project to understand the impact that all living microorganisms within the human body may have on health and disease.5 These microorganisms, which consist of 10-100 trillion cells and comprise more than 10,0000 species, are generally not harmful but beneficial, and often are even essential to our health and wellbeing.6 


To gain more perspective on the volume and significance of this microbial community, consider this example: In an average human body, bacteria that comprise a large portion of our vast microbial communities are 10x more prevalent than cells in the human body; furthermore, they encode about 1,000 more genes compared to the human genome. However, because of their small size, bacteria and other microorganisms make up only about 1-3 percent of our body mass, something that translates to 2-6 pounds of bacteria in a 200-pound adult, which is still significant.

The analysis of a microbial community is also considered BIG data.


In comparison to a genetic test, a microbiome test measures the composition and activity of either a sup-population or the entire population of the microorganisms in particular locations. This means that during a microbiome test, part of the microbial DNA or the whole microbial DNA is quantified and analyzed. Research has demonstrated that the levels and activity of specific microbes in our bodies play essential roles in our state of health or disease. 


In the human gut, for example, individuals who suffer from intestinal conditions, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD), present with specific bacterial imbalances and have a much smaller diversity than healthy controls.7 On the skin, research has shown the composition of the microbiota depends on age and sex as well as climate conditions like temperature and humidity, antibiotic treatment, or cosmetics, soaps, and hygienic product usage.8


Currently, the most commonly used microbiome tests are designed to assess the gut microbiome, i.e., the levels, composition, and activity of the microorganisms that inhabit your digestive tract. These tests can be grouped into the following categories depending on the complexity, accuracy, depth of technology, and resolution of results you desire:


  • Stool test. A stool test uses a stool sample sent to a laboratory for microscopic, chemical, and/or microbiological testing. It can also check for color, consistency, amount, shape, odor, and the presence of mucus. Depending on the test, pH, presence of blood, fat, fiber, bile, white blood cells, and sugars may also be checked. A stool culture is done to check for potential bacterial or other infections. A stool test is a routine evaluation in a clinic where a doctor may order it to screen for colon cancer, diagnose pancreatic conditions, or GI conditions such as IBD or IBS, assess nutrient absorption, and/or detect parasitic infections.


Gut microbiome tests – they are easy to do too! 

The following gut microbiome tests are offered as direct-to-consumer tests and can be collected at home. These are categorized based on the sequencing technology of the sample:


  • 16S sequencing-based DNA gut microbiome test: This sequencing reads a particular gene that is highly preserved among bacterial populations and is used for community reconstruction and representation in a sample. It provides a view of the known bacterial species and some of their functional capabilities in a sample. Depending on the report provided, you may gain insights as to which bacteria can cause potential imbalances, infections, or dysbiosis in your gut flora. 
  • Next-gen RNA gut microbiome test (metatranscriptomic test): This sequencing analyzes the RNA of your gut microbes. RNA refers to the piece of DNA that has the potential to turn into protein and reflects the microbial activity and metabolism in your gut. It is a high-resolution test and can detect live microorganisms and examine their function. However, it tends to lose viability and resolution compared to DNA sequencing because RNA is more unstable than DNA, and because it provides information only on elements of the DNA that get converted to RNA.
  • Next-gen shotgun-based DNA gut microbiome test (metagenomic test): This sequencing examines the entire DNA of your gut microbes. Similar to the whole genome genetic tests, the shotgun-based DNA microbiome test reads the whole DNA of your gut community and is not limited to specific or known regions (like RNA testing). This technology provides more detailed information and at a much higher resolution level. With the metagenomic gut microbiome sequencing technology, you get:
    • Identification of the entire bacterial population down to the strain level
    • Identification of viruses, archaea, and fungi, as well as their metabolic activity and functionality 
    • Examination of unknown populations within your gut community that are unique to you and may be responsible for conditions or problematic symptoms
    •  Ability to check microbial activity and metabolic potential via functional pathway analysis and other advanced computational methods 


GutbioTM by Onegevity is a next-gen shotgun-based DNA gut microbiome test you can do at home. It utilizes the latest high-throughput DNA sequencing technologies to read the entire DNA of your gut microbial community and provide you with an accurate, complete, and detailed microorganism breakdown, information about your risk for inflammation, gut probiotic levels, gut diversity, and metabolic potential to produce micronutrients and fatty acids. Gutbio takes into account relevant information from your profile such as allergies, sensitivities, or other conditions that may affect your gut, and with the power of machine learning and current research, your Gutbio report provides personalized nutritional solutions (diet and dietary supplements) to support the unique composition and activity of your gut microbial community. The goal is to optimize your gut, total health, and wellbeing.


PerformbioTM by Onegevity also utilizes the next-gen metagenomic sequencing for the gut microbiome in combination with established blood and saliva biomarkers and a detailed self-reported profile to show users various aspects of health and how they relate to each other. Performbio uses advanced data analytics to evaluate your gut’s DNA composition, functionality, and metabolic ability along with your healthy blood levels of relevant biomarkers and your body’s ability to adapt to various stressors: physical activity, mental/emotional, sleep, and nutrition. Cutting-edge data integration provides insights and recommendations on how to optimize your gut microbial community, digestion, blood nutrient levels, and hormones, to feel better, recover faster, train harder, and optimize human performance.




References


1.        Katsanis SH, Katsanis N. Molecular genetic testing and the future of clinical genomics. Nat Rev Genet. 2013;14(6):415-426. doi:10.1038/nrg3493

2.        Dugoff L, Norton ME, Kuller JA. The use of chromosomal microarray for prenatal diagnosis. Am J Obstet Gynecol. 2016;215(4):B2-B9. doi:10.1016/j.ajog.2016.07.016

3.        MayoClinic on genetic testing. https://www.mayoclinic.org/tests-procedures/genetic-testing/about/pac-20384827.

4.        NIH on DNA sequencing. https://ghr.nlm.nih.gov/primer/testing/sequencing.

5.        Turnbaugh PJ, Ley RE, Hamady M,et al. The Human Microbiome Project. Nature. 2007. doi:10.1038/nature06244

6.        Ursell LK, Metcalf JL, Parfrey LW, Knight R. Defining the human microbiome. Nutr Rev. 2012;70(SUPPL. 1):S38. doi:10.1111/j.1753-4887.2012.00493.x

7.        Presti A Lo, Zorzi F, Chierico F Del, et al. Fecal and mucosal microbiota profiling in irritable bowel syndrome and inflammatory bowel disease. Front Microbiol. 2019;10(JULY). doi:10.3389/fmicb.2019.01655

8.        Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011;9(4):244-253. doi:10.1038/nrmicro2537