23 and ALL Of Us: Personalized Medicine via Microbiome Sequencing

May 22, 2018


Move over silicon, the next big thing is microscopic! Microbes are taking over the biotech industry contributing their unique characteristics toward a diverse array of applications, technologies, and new startup ventures. From influencing personalized medicine, improving agriculture and decomposing previously nondegradable plastics to bio-production of fuels and 3D printed materials, microbes have infiltrated a slew of industries. This multi-part series aims to highlight the amazing ways microbes are being utilized in biotechnology. No doubt about it, microbiology is the technology buzzword of 2018.

In our first article of our MICROBIOtechnology I’ll discuss microbiome-based technologies: how to measure and manipulate our microbial cohabiitants and use that information to inform health decisions.

Personalized Medicine via Microbiome Sequencing

The personalized medicine market is booming, with countless companies and startups monetizing the technological advances in DNA sequencing that make sequencing and annotating  your personalized genome quick and affordable. These companies utilize the fact that human DNA is about 99.5% identical from person to person, but small variants among these genes are what make people unique. What many of these companies and their consumers fail to realize is that all of the proteins and enzymes found in our bodies cannot be accounted for by only our own DNA. Instead, our genomes contribute to the body’s metagenome, or the whole collection of genes found on our body, which also includes all of the bacteria, archaea, and even parasites living on and within us. On average there are at least as many microbial cells in and on the human body as there are human cells, and when that gets translated into numbers of genes, the equates to about 150 times more microbial genes than the human genome. This means that a lot of those enzymes and proteins on and in our body (like those in our gastrointestinal tract) are not actually made by us!

While there may be only 0.5% difference between person to person in terms of human genes, the metagenome differs by as much as 50%. Thus, disease may just as likely—if not more likely—be attributed to the products of our metagenome than our own genomes. MetaHIT, a consortium of 13 academics and industry professionals across 8 countries, is trying to pry apart the metagenomic causes of human disease. MetaHIT’s main objective is “to establish associations between the genes of the human intestinal microbiota and our health and disease.” Dr. Dusko Ehrlich, a project coordinator for MetaHIT, said that the analysis of the metagenome has great potential to be a diagnostic tool against disease, specifically because the variability of the metagenome between people is so much higher than the actual genome. Ehrlich told Nature News, “If the variability [from person to person] is higher, you’re more likely to find a relevant signal.”

Molding Microbes to Your Needs

There is also a potential for altering the metagenome as a simpler alternative to altering the products of genes containing SNPs (Single Nucleotide Polymorphisms) which can lead to malfunctioning proteins and genetic disorders. While altering the genetic expression of genes within humans is difficult, expression of certain genes in the metagenome can be altered by changing the gut microbe composition to remove the species that secretes a certain product.

Another way you can nudge the composition of microbiota in the intestine is to alter your nutritional intake. Humans are not evolutionarily equipped to digest on our own much of what we consume. Microbes in our intestines extract and make available to us calories, nutrients, and vitamins from food we would otherwise not be able to digest. Consequently, these microbes also play a part in digestion issues, weight gain, mood, and even how our body absorbs medicine.

Drugging the Microbiome

Dr. Matthew Redinbo from the University of North Carolina at Chapel Hill is studying this microbiome effect on drug efficacy- specifically the effect of microbes on the body’s processing of non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin, ibuprofen, and naproxen. A major issue with these over-the-counter pain relievers is that they damage the intestinal lining and can lead to severe complications, such as intestinal bleeding. Redinbo studies the effect of the microbiome on a specific NSAID, diclofenac, which can damage the intestine so badly that the contents of the intestine leak out and into the abdominal cavity, a side effect called anastomotic leakage. Redinbo and colleague, Dr. Harry van Goor of the University of Groningen in the Netherlands, found that the toxicity of diclofenac is due to reactivation of break-down products by enzymes produced by- you guessed it- gut microbes. Specifically, certain species of intestinal microbes make enzymes called β-glucuronidases that remove a sugar from the break-down product of diclofenac, which makes the product toxic. This group of microbial enzymes can be stopped by using β-glucuronidase inhibitors to prevent the toxicity of diclofenac. So, without altering the human genome, or any of its products, the efficacy and safety of our medicines can be improved significantly. This type of metagenomic and metaproteomic alteration can be used for other chemotherapies that produce highly toxic molecules which are reactivated within the intestine.

Microbiome Sequencing in a Kit

There is much to be learned from examining the microbiome of humans and analyzing the correlation with certain diseases. Another project like MetaHIT is the NIH initiative called The Human Microbiome Project that aims “to generate resources to facilitate characterization of the human microbiota to further our understanding of how the microbiome impacts human health and disease.” If you’re interested in analyzing your own microbes there are ways of doing that as well. Several companies, including a Silicon Valley startup called uBiome, and the crowd-sourced American Gut, will sequence your bacteria. The founders of these biotechs think that microbiome sequencing will one day become just as common as drawing blood- and just as medically necessary for diagnosis.

There is accumulating evidence that our microbiome plays a large role in the way our bodies function, thus, understanding the links between health, disease, and microbiota is a necessary step in the path to personalized medicine. Lap Ho, a microbiologist studying the effects of gut microbiota on the development of alzheimers disease, summarized the importance of understanding what microbial composition means for human medicine: “There is increasing interest to identify and characterize causal linkages between changes in microbial populations and the onset/progression of specific disease conditions. Our new understanding may lead to more focused and effective treatments.” As evidenced by the booming business of sequencing your microbiome (and even that of your pets!), the biotech industry certainly agrees that there is vast potential for this field now and in the future.

Stay tuned for more articles in our MICROBIOtechnology series coming soon!

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Author: Monika Buczek

Monika Buczek
Senior Contributor Dr. Monika Buczek completed her doctoral research in Molecular, Cellular and Developmental Biology and now works in translational cancer research.