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Genome Metabolic Modeling-- What Is It and How Does Onegevity Use It?

Laura Kunces, PhD, RD
Onegevity

A gut microbiome sample can tell us a lot. By directly and precisely measuring the DNA from a stool sample, we can analyze a less biased view of the totality of one’s gut ecosystem-- including phages, bacteria, fungi, and other genetic elements such as structural changes-- like variants and copy number changes to the DNA of those species. Unlike other companies who may be looking at RNA, when we look at the DNA, we see a more precise measure of one’s health-- not just how a recent food or incident may have affected one’s system.


In addition to the direct measuring of microorganisms, Onegevity uses genome mapping to understand microbe to microbe, diet to microbe, and microbe to host (you) interactions. To do so, it requires three essential components which we see as the crux of our company: 

  1. Our advanced, state-of-the-art metagenomic sequencing technology that allows for direct and virtual mapping of one’s genetic makeup
  2. Statistical and machine learning algorithm construction for prediction modeling
  3. Curation of the scientific literature on the gut microbiome for regular updates of our database to make the most accurate and current recommendations


What is genome modeling, and how is it used?

Your gut microbe community, your genes, lifestyle, environment, and your diet all interact to dictate what is being produced, what is being stored, and what is being used in your body daily. Through numerous research studies using humans, we can confidently use established algorithms to model the human gut microbiome at the genome level-- examining the bi-directional and dynamic interactions of microbe to microbe, microbe to host (you), and microbes to diet that determine your body’s capacity to produce metabolites. The microbes and their metabolites are responsible for a multitude of metabolic functions, including meeting physical energy demands, digestion, hormone regulation, metabolism, and affecting mental capabilities, and the for chronic disease.  


Onegevity uses proprietary algorithms to account for the two ways in which the gut microbiome can be modeled--- by looking at the microbial species in the gut work that together-- for example, species that produce or consume metabolites, and by also looking at the individual gut metabolite levels. The algorithms are built upon machine learning techniques, the vast scientific literature database, the human microbiome project, and other large-scale scientific initiatives. The volume of these databases is forever growing, and our scientific team reads, evaluates, tags, and assigns articles and new data within our system regularly, making sure we have the most up-to-date information and our machine learning capabilities can continuously grow smarter.



Which bacteria are most important?

Species from predominant phyla in the human gut tend to offer the most insight into one’s capacity to make and maintain amino acid, bile acid, B-vitamin, and SCFA production in the gut. The current research has found the following five bacterial species to play a significant role in many of the metabolic processes in health, disease prevention, and metabolism, specifically your body’s capability to produce amino acids: B. adolescentis, B. thetaiotaomicron, R. bromii, E. rectale and F. prausnitzii. For example, through targeted metabolomic research quantifying the fermentative activity of bacteria, it’s been found that these bacteria (in specific abundance and ratios) can synthesize significantly higher levels of essential amino acids (valine, leucine, methionine, lysine, and phenylalanine) compared to non-essential amino acids (serine, tyrosine, and threonine).1 Interestingly, it is the same bacterial species along with B. thetaiotaomicron that influences your capability to produce SCFAs, specifically butyrate, acetate, and propionate too. 


Research has shown that a handful of bacterial species are capable of producing certain amino acids, bile acids, B-vitamins, or SCFAs even above 41% of the total gut metabolite levels, with as little as one species being the main contributor depending on the metabolite.1 


How does one’s microbial gene richness or gut diversity play a role?

When considering the impact of diet on microbiota composition, gene richness plays an important role. Gene richness is considered the number of unique bacterial genes harbored in the gut microbiota and thereby different microbial communities. One is typically stratified as having a high or low gene richness level. This is different from a gut diversity (a measurement of microbial richness combined with evenness, meaning it takes into account not only how many microbial species are present but also how evenly distributed the numbers of each species are). It can dictate the way one responds to a dietary intervention. 


High and low gene richness can influence baseline and post-intervention metabolite production levels. However, even if one starts with a lower gene richness level, changes in metabolite production can be achieved, but it may be a different extent than with a higher gene richness (depending on the metabolite).1 


Onegevity’s advanced whole-genome shotgun sequencing technology allows us to measure to that extent that it accounts for gene richness in your report. Metagenomic data can pinpoint the exact species that influence metabolite production (or are being influenced) from interactions with other microbes or a diet in as little as a few weeks. 


Our dietary recommendations are made to include ways to increase your gene richness depending on your bacteria abundance and ratios and may include dietary patterns that incorporate dairy products, more vegetables, white meat, fish, eggs, oils, or butter. In some instances, one may be recommended a diet that significantly reduces carbohydrate sources.


Can gut metabolite levels predict blood levels?

Research has shown serum metabolites can be predicted from gut metabolites. With certain dietary interventions, gut amino acids, bile acids, cholesterol, and SCFAs can be significantly altered to a more desirable level. Similarly, certain amino acids have also been correlated to other clinical variables, including BMI, body composition, insulin resistance, cholesterol synthesis, inflammation, and more.1 



Why are SCFAs, bile acids, amino acids, cholesterol, and B-vitamins from the gut important? 

We offer a measure of their capability to be produced based on the gut bacteria present in your system because each of these influences your metabolism, energy, and ultimately should be important reference points for your diet. Based on this, we can recommend a better diet for you to follow so you can optimize their abundance in your gut, have better probiotic production, and know if you need nutritional supplementation or not.


Here are the basics of why these components are presented in a Onegevity report:


Amino Acids--Dietary proteins and amino acids are important substrates for microbial fermentation in the colon. They provide an essential nitrogen source for the microbiota and the host (you), which is a necessary element for DNA synthesis. 


Bile Acids-- Essential steroid acids synthesized by the liver to support dietary fat metabolism. Too much or too little affects gut motility, lipid metabolism, and vitamin and hormone blood levels.


B-vitamins-- Probiotic bacteria can produce some B-vitamins which otherwise would need to come from one’s diet. These vitamins are needed for energy and cellular metabolism, are used as precursors for certain coenzymes in many redox reactions, and can help maintain normal homocysteine levels. 


SCFAs-- Serving as the main energy source for colonocytes, SCFAs are therefore essential for gastrointestinal health and immune homeostasis. Onegevity measures the gut microbiota from the proximal colon, where they are found to be in their highest abundance and most representative of your production capability.2 


The new Performbio by Onegevity has unique sections of the report that every high-performer is going to love: a calculated value of your capacity to produce amino acids, bile acids, B-vitamins, and short-chain fatty acids --  based on your gut microbiota population, blood and saliva test results, gene interactions, and the foods/supplements you have been consuming. Gutbio continues to report on the important SCFAs and B-vitamins in which those suffering from Irritable Bowel Syndrome and other GI conditions should measure.


1.     Shoaie S, Ghaffari P, Kovatcheva-Datchary P, et al. Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome. Cell Metab. 2015;22(2):320-331.

2.     Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The role of short-chain fatty acids in health and disease. Adv Immunol. 2014;121:91-119.