14 June 2019

Biotech in a big way

How biomedical startups are going to make money on the contents of the intestine

Daria Shipacheva, Forbes, 12.06.2019

About 10 trillion bacteria live in the human intestine, which constantly interact with the body of the "host". The gut microbiome can cause obesity, depression, and even cancer. Recently, some of the scientific discoveries in this field have reached the phase of commercial application.

In 2003, the Human Genome project was completed – a huge international study with the help of which it was possible to decipher the complete sequence of the human genome. Now geneticists and bioinformatics have a huge amount of data that can be studied in connection with the risk of various diseases.

But after the "Human Genome", biologists took up a new project – the "Human Microbiome". Microbiologists have drawn attention to the fact that a huge number of bacteria live in symbiosis in the human body, whose DNA has not yet been completely studied. At the same time, there is a growing amount of evidence in favor of the fact that the genome of bacteria somehow affects our health: in particular, the risk of developing acquired diseases such as type II diabetes, obesity, cancer. Moreover, the composition of the microbiota can increase or decrease the likelihood that you will develop diseases to which there is already a hereditary predisposition – for example, ulcerative colitis, Crohn's disease, depression.

But how can we study the interaction of bacteria – and there are about 1000 of their species – with our body in real time? This is where the Organ Chip technology comes to the rescue.

The intestine in miniature

A team of researchers from Harvard has developed an organ-on-a-chip technology. Its essence is as follows: a colony of bacteria, which is extracted from a stool sample, is placed on a small area of epithelial tissue. This can be said to be a miniature intestine: a piece of tissue that lines the intestinal walls, is supplied with blood vessels and is preserved in stable anaerobic conditions for at least 5 days.

To create an Organ Chip, a team from Harvard took as a basis a device of computer microchips. The "organ-on-a–chip" itself is located on a flexible polymer plate - it is about the size of a laptop memory card. The plate contains cavities – microfluidic channels, with the help of which it is possible to recreate the system of nutrition and metabolism in tissues similar to what happens in the body.

Next, cells of the selected human organ are placed in one of the channels – it can be skin, intestines, lung, bone marrow. Then an artificial circulatory system is recreated in the adjacent channel: for this, scientists use living endothelial cells – those cells that line the inner surface of our vessels.


Finally, the final stage is to recreate for the "organ–on-a-chip" the conditions in which human organs live in reality. In the case of the "mini-intestine", researchers have created a special anaerobic chamber for it, which simulates conditions with a low oxygen content for intestinal cells – this is how it works in the body, while maintaining a normal oxygen concentration in the area of artificial vessels.

Why all this?

Thanks to the new technology, scientists will be able to trace how intestinal bacteria develop in the natural environment. What will happen if the number of any subpopulation of microbes sharply decreases? And if someone else's microbiome is transplanted into the "intestine", how will it affect the surrounding tissues at the cellular and molecular level? Researchers will also be able to see which metabolites – waste products – are secreted by bacteria of different species. These metabolites may be the key to understanding exactly how the microbiome affects the development of diseases in humans.

Another "feature" of the Organ Chip technology is that it opens up new opportunities for personalized medicine. The microbiome of different people is infinitely diverse, and it is still difficult to find a common solution for the "ideal composition" of intestinal bacteria. Since for the Organ Chip technology, scientists take cells from the intestines of a particular patient, they will be able to study the individual reactions of his microbiome and select personalized therapy.

In the future, the technology will be able to help in the diagnosis and treatment of people with colorectal cancer, inflammatory bowel diseases, obesity, liver cirrhosis, type 2 diabetes, depression. But today, according to the researchers, they still do not have enough information to move on to practice. Although experiments on animals give encouraging results: in particular, it was possible to cause symptoms of depression in rats by transplanting bacteria from their more depressed counterparts. Whether it will be possible to do the reverse trick, and even on people, remains a question.

Who owns the bacteria and excrement market

Emulate, Inc., a startup launched by the Viss Institute of Harvard University, has recently appeared in the United States, thereby developing the Ogan Chip technology. Emulate will now focus on developing and commercializing the technology, including for the study of the human microbiome.

The market for private microbiome testing is still in its infancy. There are not so many major players around the world who are ready to give customers some recommendations based on the analysis of the chair. And one of them is from Russia. uBiome offers several products: microbiome testing "in a vacuum", a three–time test – before, during and after lifestyle changes recommended by the service, a subscription to regular testing of intestinal bacteria, as well as microbiome analysis on different parts of the body, including skin and genitals. The issue price for a one–time purchase is from $89 to $399.

Service Viome focuses on using microbiome analysis to establish a diet and lose weight. An application is "screwed" to the test for $199, in which the user is given tips on nutrition and dietary supplements.

Finally, the Russian Atlasbiomed, which is actively exploring the UK market and other foreign markets, offers a comprehensive service. In addition to the microbiome test for $ 150 dollars, you can order a genetic test – and recommendations for nutrition, prevention and treatment of diseases will take into account both the DNA of your bacteria and your own.

The American company InSilico Medicine, led by Russian scientist Alex Zhavoronkov, uses microbiome and neural network analyses to determine a person's age. Already, their technology "guesses" the age of intestinal bacteria with an accuracy of up to 4 years. In the future, the results of such tests can be used to give clients recommendations for life extension – this is the main mission of InSilico Medicine.

True, the financial performance of companies working with microbiome analyses leaves much to be desired. One of the largest players in this field, uBiome, now has annual revenue of $32 million, while their competitor Viome has a turnover of only $3.4 million. Nevertheless, both companies have received investments in tens of millions of dollars for development – so, perhaps, we will soon see an active growth of the microbiome research market.

The development of companies producing such tests is hindered, firstly, by their price (incomparable with the analysis for "dysbiosis" in the polyclinic!), and secondly, by the insufficient development of technology. But the more data these companies and research scientists have, the faster the "science of faeces" will have a real practical application. And then, according to the calculations of microbiologists, a simple stool analysis will be able to replace many expensive and invasive diagnostic methods – and will also be the key to the treatment of certain diseases.

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