Juan Basterra (Mikrobiomik) | "In the last 10 years, decisive steps have been taken to understand and appreciate the role of our gut microbiota"

During the last decade, the term "microbiome" has gained popularity thanks to scientific advances that have highlighted its crucial role in human and animal health. In the case of the gut microbiota, decisive steps have been taken during this time to understand and appreciate its role in ensuring our health. The increase in this knowledge has allowed us to identify more than 300 diseases related to alterations or changes in the microbiota.

On the occasion of World Microbiome Day on June 27th, we interviewed Juan Basterra, CEO de Mikrobiomik, a biotechnology company created to research, develop, and manufacture biological drugs based on gut microbiota. 

AseBio: What is the microbiome, and why does it play such an important role in human health?

Juan Basterra: The microbiota is the collection of microorganisms that live and coexist inside the human body. The microbiome is the genome of all the microorganisms in the microbiota. The term microbiome is much broader than microbiota, as it includes the entire microbial communities, genes, and metabolites, as well as the environmental conditions that surround them. We can talk about five main microbiotas: the gut microbiota, which includes a community of microscopic organisms living inside our digestive tract, particularly in our colon; the respiratory microbiota; the skin microbiota; the urogenital microbiota; and the oral microbiota.

AseBio: How does it differ from the microbiota?

Juan Basterra: The microbiota is the collection of all microorganisms that are part of our organism (bacteria, fungi, viruses, archaea, viruses, fungi, and protists). Humans have the same number of cells as bacteria. We are half human, half microbes. The greatest bacterial diversity is found in our gastrointestinal tract.

AseBio: How has our understanding of the microbiome changed in recent years? What role has biotechnology played?

Juan Basterra: The American biologist Jeffrey Gordon, a pioneer in this field and promoter of the Human Microbiome Project, discovered that the main function of the bacteria that inhabit our intestines is to prevent diseases. The various studies published by this doctor from the University of Chicago over the last 20 years have confirmed that an imbalance in the microbiota is related to diseases such as diabetes, obesity, or malnutrition, but also affects our neurological and immune development.

Moreover, in the last 10 years, decisive steps have been taken to understand and appreciate the role our gut microbiota plays, which would not have been possible without applying previous knowledge about other microorganisms and their metabolic processes. In the scientific world, there is no longer any doubt about the connection between the gut and the brain, as our gut contains more than 100 million neurons, more neurons than the spinal cord. Additionally, it is known that the gut and the brain communicate and form what is called the 'gut-brain axis,' which influences many aspects of our neurons. This advance can be fundamental for addressing potential treatments for neurodegenerative diseases or others related to our mental health, such as anxiety and depression.

It is also known that the gut microbiota determines blood glucose levels and that the circadian cycle is connected with the rhythm of the gut microbiota, which opens up new possibilities in the field of diabetes, for example. Immunologically, researchers have also observed that the gut microbiota can modulate the toxicity of cancer therapy, and that people who respond to immunotherapy have a more diversified gut microbiota, which is linked to a high fiber intake.

More than 300 diseases related to alterations or changes in the microbiota have been described. Often, we do not know if this change in the microbiota is the cause or the effect of the disease, but there is increasing data supporting a relationship between the two.

Scientific advances in this exceptional field focus on obtaining preventive, diagnostic, and therapeutic measures based on the microbiota, although the microbiota can play a fundamental role in treating many diseases whose cause is still unknown. There is a wide field of research ahead that will undoubtedly translate into important clinical developments. And we are contributing our grain of sand.

At Mikrobiomik, we have developed the first biological drug (MBK-01) in oral capsules based on gut microbiota, which will be marketed in the EU with FSPIM (Full Spectrum & Purified Intestinal Microbiota) technology, containing the entire bacterial ecosystem from a validated healthy donor, in a single capsule. Our therapeutic approach is based on the transplantation of gut microbiota, which is not new (it was already practiced by traditional Chinese doctors 1,700 years ago). But our contribution is to make the future a reality with our oral capsules of gut microbiota with the highest standards of safety and quality, following all protocols and procedures inherent in the development of medicines.

AseBio: What recent advances have been made in microbiome research?

Juan Basterra: A few weeks ago, a study led by the Spanish National Research Council (CSIC) was published, discovering the presence of bacterial amyloids associated with Parkinson's disease in the gut microbiota. The finding, published in the journal Nature Communications, could provide tools for early diagnosis of this pathology, which affects more than seven million people worldwide. It is a significant milestone because age-related neurodegenerative diseases involving amyloid aggregation remain one of the greatest challenges of modern medicine.

In the future, we at Mikrobiomik aim to address such diseases with our biological drug MBK-01, from improving the quality of life for autistic patients to influencing the immune response in ALS patients.
 

AseBio: Mikrobiomik has the first and only GMP (Good Manufacturing Practices) facility exclusively dedicated to manufacturing biological drugs derived from gut microbiota. How are these made? How do you select the samples that are ultimately suitable for developing these drugs?

Juan Basterra: At Mikrobiomik, we have initiated a new investment round of up to eight million euros to construct a new industrial-scale production plant. Currently, we have a limited production GMP pilot plant for MBK-01, authorized to produce MBK-01 exclusively for clinical trials and compassionate use. Building a new plant will allow us to multiply our current production tenfold to meet the expected market demand.

Mikrobiomik's roadmap, in addition to expanding production facilities, includes creating a pioneering network of stool donation centers in Spain. This aspect is also essential for us because, from the stools and through an innovative technological process, we at Mikrobiomik separate and purify the microbiota, finally transforming it into a 250 mg capsule. The stool donation process is rigorously controlled to ensure that only the stools of healthy, validated, and committed donors are used, who are willing to make 2-5 donations per week for two months. A medical team oversees all requirements: online health questionnaire, personal medical interview with donors, and medical tests (including blood and stool analysis).

AseBio: Mikrobiomik is working to become the first company globally to market the first biological drug based on gut microbiota in the European Union for the indication of recurrence of 'Clostridium difficile,' through the administration of MBK-01 (4 capsules of lyophilized fecal microbiota) in a single dose. Where do you stand currently?

Juan Basterra: We proudly say that, for the first time in the history of the pharmaceutical industry in the Basque Country, a drug researched, developed, and produced in Bizkaia has been classified by the EMA (European Medicines Agency) as a new active substance, granting us 10 years of market exclusivity and allowing us to follow a centralized authorization procedure. This will enable MBK-01 to be available to all patients and healthcare professionals in the EU based on a single marketing authorization valid in all EU member states.

Currently, we have already started the regulatory process and expect to obtain marketing authorization from the European Commission in the first quarter of 2025, pending a favorable recommendation from the EMA expected in the second half of 2024. We will launch MBK-01 in the first half of 2025, after years of effort and thanks to the talent of the Mikrobiomik team, of which I am very proud.

However, the compassionate use of MBK-01 for Clostridium difficile infection (CDI) is currently authorized in Spain by the AEMPS. This compassionate use program has benefited dozens of patients to date. 

AseBio: What challenges does microbiome research currently face? Based on your experience, which areas of microbiome research do you consider most promising for the future?

Juan Basterra: It is a field with extraordinary potential. Advances are being made in researching the molecules produced by the millions of microorganisms living in our digestive system, their ability to interfere with our proteins, and their influence on disease development, including neurodegenerative diseases, for example.

Additionally, studying their influence on the visible traits resulting from the interaction of genotype and environment will contribute to the advancement of personalized medicine. In the future, this will include an analysis of the microbiome - the genotype of the individual microbiota - to propose more personalized treatments that can also consider the impact of microbes on each treated subject.

In the case of Mikrobiomik, we aim to scientifically validate the potential of our first biological drug based on gut microbiota, MBK-01, for various pathologies. We want to evaluate if restoring or replacing a healthy microbiota in a simple and effective way can be a therapeutic alternative in managing various diseases.

For now, we will be the first company in the world to bring to market the first biological drug based on gut microbiota (MBK-01) as a treatment for primary or recurrent Clostridium difficile infection (CDI), which causes repeated episodes of diarrhea, abdominal pain, and fever.

Our pipeline includes three other indications: treating metabolic dysfunction associated with steatohepatitis (MASH), also known as fatty liver, whose phase II clinical trial will begin in 2024, as well as a phase IIa for treating uncomplicated acute diverticulitis. We also plan to start a proof-of-concept study for treating metastatic colorectal cancer that does not respond to 2-3 lines of treatment.