The project aims to create the world’s first microbiome-based drug produced in a bioreactor, eliminating the need for traditional faecal transplants and enabling more precise, scalable therapies.

“Scientists are working on a biosynthetic supermicrobiome useful in the treatment of many conditions, such as cancer, autoimmune diseases, Parkinson's disease, and antibiotic-resistant infections. We have focused primarily on antibiotic-resistant bacteria,” says Jarosław Biliński, PhD.

Polish Press Agency: You and your team are working on the world's first biosynthetic drug produced from the gut microbiome, obtained from specially selected donors, with the so-called supermicrobiome. Until now, doctors have recommended a complete faecal transplant, which not all patients accept. The new drug is to be administered orally and intended to help with various conditions, including cancer, autoimmune diseases, and antibiotic-resistant infections.

Jarosław Biliński, PhD: We want to recreate the gut microbiome in a bioreactor to eliminate the need to collect faecal samples from donors, which is very difficult and expensive. Of the healthy individuals who volunteer, only 0.5% can become such donors due to the stringent requirements that must be met.

Polish Press Agency: Why is that?

J.B.: Only super-healthy individuals can be supermicrobiome donors, and the number of such people is decreasing due to the increasing prevalence of unhealthy lifestyles. This causes the microbiome to deplete its beneficial bacteria, while also containing bacteria resistant to various antibiotics and viruses that can be transmitted to the recipient. Hence the idea of developing a biosynthetic microbiome that could be grown in a bioreactor. It would be a kind of self-renewing medicine.

Polish Press Agency: Is it really that difficult? There are bioreactors that produce drugs.

J.B.: In the case of the microbiome, it is very difficult. The bacteria in our intestines are anaerobic, so there cannot be any access to oxygen in a bioreactor. Suitable media are also required for bacteria to multiply - we essentially need to replicate the physical and chemical environment of the intestines, which is a very complex matter. If we succeed, we want to produce biosynthetic drugs from this biosynthetic microbiome.

Polish Press Agency: Who will receive them?

J.B.: We intend to produce drugs with a specific composition of bacteria, selected based on their DNA and genes, as well as the functions they perform and the substances they produce, useful in the treatment of a specific disease. We can calculate this using artificial intelligence algorithms.

Polish Press Agency: Are these drugs intended for universal use, or will they be tailored to a specific patient?

J.B.: We would primarily like to obtain a universal microbiome as the ecosystem basis for any subsequent drug from the microbiome, so it will not be a single drug tailored to a specific patient. Rather, our goal is to obtain a drug useful in treating a specific disease. For example, one that improves the effectiveness of cancer treatment using immunotherapy. Another drug, on the other hand, would be useful in treating irritable bowel syndrome.

Polish Press Agency: How can we assess which microbiome composition is more useful in treating a specific disease?

J.B.: First, we determined the composition of a reference supermicrobiome based on the microbiome of selected superdonors. This way, we created our own standard for what we considered a very healthy microbiome. We are also conducting studies on patients using the donors' supermicrobiome to determine whether it works and what is actually effective in this microbiome. For example, we are already conducting a third study aimed at eliminating antibiotic-resistant bacteria from the gastrointestinal tract.

Polish Press Agency: What does it involve?

J.B.: In this research, we process donor faeces into a microbiome suspension encapsulated in capsules and then administer it to patients. This is done with the approval of the bioethics committee, as all our studies are strictly controlled. We observe what happens when we administer the superdonor microbes to patients with antibiotic-resistant bacteria. We check whether the patient's microbiome changes and whether resistant bacteria are removed. We also analyse why some patients fail to recover. In this way, we try to determine what is needed for our therapy to be effective - to eliminate harmful bacteria, cure a disease, or support cancer treatment.

Polish Press Agency: How is this done?

J.B.: Through high-throughput computation of data from genomic, metabolomic, and other studies on the AI-based platform we have created. Soon, we will have completed more than a dozen so-called proof-of-concept studies, meaning they will serve to confirm our concept - whether the microbiome works in a given clinical indication or not. We have data indicating that the microbiome should be effective in certain diseases, but this requires rigorous experimental testing.

Polish Press Agency: Do we already know which diseases such a supermicrobiome would be useful for?

J.B.: We focused primarily on antibiotic-resistant bacteria because they pose a growing challenge to healthcare. At this point, 17% of people worldwide, or 1.3 billion, host at least one such dangerous bacterium, resistant to clinically relevant antibiotics - meaning all oral antibiotics, or indeed all antibiotics invented by humans. Therefore, patient deaths due to single-bacterial, antibiotic-resistant infections are becoming increasingly common. And it seemed we had everything and could treat bacterial infections.

Polish Press Agency: What about other conditions?

J.B.: We also deal with immuno-oncology and transplantology. Bone marrow transplantation is used to treat some cancers, allowing the bone marrow to properly recognize and destroy cancer cells again. Then, the patient, now cancer-free and under monitoring for the development of cancer cells, functions normally. However, sometimes the immune system misidentifies what is foreign and what is self. In this case, we have two applications. One is a complication that occurs after a bone marrow transplant. It turns out that the microbiome has a huge impact on how the new bone marrow, and with it the new immune cells, will behave after the transplant. It also influences whether the donor's immune cells, generated by the new bone marrow, will recognize the recipient's cells and potentially destroy them as foreign. This is called graft-versus-host disease, meaning against the patient who received it. It destroys the patient's intestines, skin, liver, or other tissues. This happens despite matching the patient and donor based on tissue compatibility. The microbiome is as much as 50% effective in restoring the immune system to normal and resetting overactive, aggressive immune cells - which translates into saving the lives of patients with this very serious complication.

Polish Press Agency: And another application?

J.B.: It is supporting immunotherapy, used in cancer treatment, which stimulates the immune system to fight cancer cells. In this case, it turned out that without the right bacteria in the gut to stimulate the immune system, this therapy is less effective. However, studies have shown that half of the patients who previously did not respond to immunotherapy can respond to it after receiving the appropriate microbiome.

Polish Press Agency: What other diseases are being analysed in terms of the microbiome?

J.B.: We are recruiting children aged 6–12 with autism spectrum disorder (ASD) for the study. The microbiome produces many neurohormones and interacts with the nervous system. We accidentally observed that in children with ASD who received a microbiome transplant due to an antibiotic-resistant infection caused by Clostridium difficile bacteria, their autism spectrum symptoms also improved. For example, they showed increased appetite and reduced gastrointestinal symptoms, stopped self-harming, began talking, and socialised. These are incredibly interesting observations, so we decided to investigate this in high-quality studies and potentially work on a biosynthetic microbiome for the autism spectrum.

Polish Press Agency: Is it possible to help premature infants, who often have weaker immune systems, in this way as well?

J.B.: We are now beginning a study involving the administration of the microbiome to premature infants to prevent severe infections and necrotising enterocolitis. They experience many infectious complications, such as pneumonia and necrotising enterocolitis, especially if they have a genetic defect. Populating their guts with a healthy microbiome should help better stimulate the immune system and protect against such complications. This is indicated by animal experiments, as well as the data we have collected.

Polish Press Agency: You recently published research on Parkinson's disease in a leading neuroscience journal.

J.B.: Yes, we administered our superdonor microbiome preparations to patients suffering from this disease. It was a double-blind study, meaning some patients received their own microbiome back as a placebo. However, neither the doctors nor the patients knew what they were receiving. This is a requirement of these trials. We demonstrated that patients experienced significant improvements in cognitive function, sexual function, and pain perception after just one administration of the donor microbiome in the Human Biome preparation. We now intend to examine the response after administering several doses of the superdonor microbiome as a continuous therapy.

Polish Press Agency: What types of people have a supermicrobiome?

J.B.: These are usually very slim people who care about their health, are physically active, and consume little meat, although we do not exclude those meat eaters. However, our observations indicate that a diet similar to vegetarianism has a beneficial effect on the microbiome. These people also rarely contract infections, which is also due to their favourable microbiome, as one influences the other. This means they live healthily and do not have a serious family history of illness. We exclude those whose first-degree relatives have suffered from cancer, autoimmune disorders, or mental health conditions. We know that the microbiome can influence these illnesses. In addition to completing an extensive questionnaire, donor candidates also undergo more than 140 blood and stool tests.

Polish Press Agency: And how can you modify your microbiome?

J.B.: Above all, maintaining a healthy lifestyle is essential. Studies conducted on thousands of volunteers show that three factors are crucial. The first is a healthy diet, preferably Mediterranean, with plenty of vegetables and fruit, with meat accounting for only a quarter of calorie intake. Adequate sleep is also important, as chronic sleep deprivation worsens many health parameters. The third most important factor is physical activity. It does not have to be intense; even 30 minutes a week is enough to improve your microbiome.

Polish Press Agency: And what is the biggest microbiome killer?

J.B.: Highly processed foods, so-called junk food. We should definitely avoid these, as they damage our microbiome the most.

Zbigniew Wojtasiński (PAP)

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