Engineered Probiotics & Human Health



The ability of a microbiome to adulterate the physiology of an organism has recently been highlighted. This is due to a dependence generated by a close symbiotic relationship, where commensal bacteria degrade products that our human genes cannot degrade, accelerating and diversifying digestion. In other words, our microbiome is proof of the success of coevolutionary strategies based on survival.


This does not necessarily mean that each person's current microbiome is the most optimal, as it is easily moldable through physical habits such as diet and exercise. In addition, each human receives a different microbiological inheritance, as they are normally acquired through the birth canal and in contact with the mother's skin during breastfeeding; without taking into account the environmental effect and coexistence with other humans or animals. It could be said then that each microbiome is different, like a fingerprint; but transformable since it changes with the circumstances. If we connect the dots, we have a very powerful tool that favors our health at different levels (metabolic, immune, homeostatic) and that is also externally modifiable. This last point is where biotechnology comes in since it is possible to design colonizing units that are associated with an improvement of a specific process or directly create a genetically modified bacterium for a specific process.


What are probiotics?


The discovery of many qualities associated with the microbiome has led biologists to develop live bacterial supplements that colonize niches in our epithelium, whether intestinal or dermal. This can sometimes be accompanied by what are known as prebiotics, or compounds used by probiotics to grow that consist primarily of non-starch polysaccharides and oligosaccharides poorly digested by human enzymes. It is well known that the more functional diversity - or genetic diversity - an organism has, the more plasticity it will have in the face of particular stress. Stresses such as opportunistic infection or indigestion could easily be avoided by an appropriate reformation of the microbiome. This could be as simple as taking a pill.


Design vs Evolution


While there are many natural probiotics already known and marketed - for example, UltraLevura (Saccharomyces boularii) or L. casei - the microbiome is not such a flimsy entity as to solve serious problems in this way. While it is true that these drugs could solve a temporary problem (such as preventing intestinal dysbiosis caused by antibiotic treatment, for example), they do not bring about a permanent improvement in the quality of life of those who take them. Our microbiome, evolved over millions of years - and perfected in the last few thousand for the change in human nutrition - is far from perfect, but it fulfills well the natural task of survival and well-being. Could we humans design a microbiome more suited to our own physiology than the one evolution has given us?


Everything seems to point to yes. There are many congenital metabolic diseases that could be cured by profound modifications of the microbiome. Not only of individual bacteria but of the proportion of species (usual or not) that cover our epithelia. There are already tools that consider "healthy microbiomes" as a cure for serious diseases, such as fecal transplants. But here we are talking about replacing a natural microbiome with an artificial one, specifically designed to treat an issue or even prevent future problems. We are talking about preventing cancer with a non-injurious treatment, for example. Because yes, some types of cancer have been shown to have a close relationship with the microbiota of the sufferer. It is estimated that 20% of malignant formations could be due to this cause, although it could be more. Let us remember that the microbiome is interconnected with elementary functions of our organism, with the nervous and immune systems, the latter being a clear protagonist in the body's response to cancer and autoimmune diseases. To talk about something more curious, recently an article appeared in Nature pointing to the possible relationship between the behavior of mammals - depressive type and dominant type - with the pattern of microbiome exhibited. We are also talking, therefore, about curing depression or related neurological diseases.


Current State & Start-ups


Currently, we are trying to elucidate the "miracle pathway" or the "key microorganism" in certain metabolic processes that can solve major health problems, including aging. For the sake of biological engineering, we have companies such as Ginkgo Bioworks, whose goal is to design customized microbes for the client. Zymergen also aims to do something similar, but with a focus on improving the existing functions of microorganisms, i.e. maximizing their efficiency. In other fields that we have also discussed in the article, we have Seres Therapeutics that tries to deal with dysbiosis by means of a pharmacological supplement that complements a failure in the microbiome. Evelo focuses on the diagnostic capabilities of the microbiome to manufacture therapies that modulate the systemic immune response.


The Future


The quality of life of human beings in the first world has increased significantly over the last two centuries. However, the industrial revolution has also led to bad habits for our microbiome such as abundant and unnecessary intake of monosaccharides, stress, and sedentary lifestyles. It is for this very reason that the near future of human beings will be marked by another technological apotheosis, which we could perfectly well call the "first biotechnological revolution", since it will be based on alleviating our bad habits and even congenital or acquired diseases exclusively through biotechnology. The concept of hologenome will gain strength in the coming years, and we will begin to understand the microorganisms that colonize us as components of our own organism.