The research of the human microbiome has made rapid progress in recent decades, from crucial studies that began in the 1970s to the start of the Human Microbiome Project in 2007. Breakthroughs have laid the groundwork for newer clinical applications, such as fecal microbiota transplantation (FMT) and advanced techniques for investigating new therapeutic pathways. According to Professor Dr. Martin J. Blaser, one of the pioneers in this field, the „microbiome revolution“ is only just beginning.
Dr. Martin J. Blaser, MD, continues to lead research and clinical studies investigating the link between the human microbiome and the most common causes of death in the United States. He suggests that interventions that manipulate the microbiome hold promise for preventing, slowing, or even curing these diseases. As the Henry Rutgers Chair of Human Microbiome and Director of the Center for Advanced Biotechnology and Medicine at Rutgers University in New Brunswick, New Jersey, Blaser is at the forefront of microbiome research.
In this interview, which has been edited for clarity, Blaser discusses where we currently stand and anticipates future developments in the field of microbiome.
Highlighting the Most Promising Applications
What current studies on the link between the human microbiome and diseases have you found particularly promising?
There are several studies, including our own, focusing on the gut-kidney axis. The gut microbiome produces or detoxifies metabolites that are toxic to the kidney, such as those involved in kidney stone formation and uremia. Modifying the microbiome to reduce uremic toxins and substrates for stone formation is a promising area of research.
What other disease states could be suitable for microbiome-based interventions?
There are diseases caused by known genetic mutations, yet there are substantial differences in clinical outcomes that could be classified as gene-environment interactions. It seems likely that microbiome variation could play a part in some of these differences, especially in certain genetic diseases.
It is now widely recognized that microbiome modification through FMT is a successful intervention in recurrent Clostridioides difficile infections. What, in your opinion, will be the next disease state to show significant efficacy using FMT?
If you visit ClinicalTrials.gov, you will find that there are 471 registered studies involving FMT. This applies to a broad spectrum of diseases, including metabolic, immunologic, autoimmune, inflammatory, degenerative, and neoplastic diseases. For a specific disease to show clear efficacy remains unclear, so we must conduct clinical trials to assess what works independently of the specific disease.
The donor’s microbiome seems crucial to the success of transplantation, and even „super donors“ have been identified. What factors do you think mainly influence microbiome transplantation?
This question is part of an emerging science based in part on classical ecological theory. At the moment, we use FMT as if there were a one-size-fits-all solution, but it probably would not provide optimal treatment for all. Just as we sort blood donors and recipients before blood transfusion, we could easily imagine a parallel approach for microbiome transplantation.
Are there diseases where it is just too far-fetched to believe that a change in the microbiome could make a difference?
The connection between the microbiome and human health is so ubiquitous that there are only a few diseases that are beyond the realm of possibility. It really is a frontier. Not that the microbiome causes everything, but understanding and manipulating it could at least alleviate or slow down certain pathological processes. For all the major causes of death in the United States – heart diseases, cancer, dementia and neurodegenerative diseases, diabetes as well as lung, liver and kidney diseases – the microbiome is currently being researched. A more promising endeavor would be preventing or curing these diseases.
Predicting the Next Phases of the „Microbiome Revolution“
Do you believe we are at a turning point with regard to the ability to manipulate or engineer the microbiome?
The microbiome is a scientific frontier that impacts the entire biosphere, encompassing human and veterinary medicine, agriculture, and the environment. It is a vast field, and knowledge is expected to gradually expand.
Are we at the point where physicians should take microbiome-related lifestyle changes into account for people with cancer, heart disease, Alzheimer’s, or other chronic diseases, or those at risk for them?
While we are still in the early stages of the „microbiome revolution,“ about which I first wrote in EMBO Reports in 2006 and then again in the Journal of Clinical Investigation in 2014, I think we will make significant progress in the next 5-10 years in all these diseases.
How will prebiotics, probiotics, and postbiotics be used to shape the microbiome?
This is a very important and active area of clinical research that needs to be expanded. Tens of millions of people use probiotics and prebiotics daily for vague indications that have rarely been tested in well-founded clinical studies. So, there is a discrepancy between what is currently claimed about the majority of probiotics and what we will actually know in the future.
How do you think the microbiome will fare compared to other factors that influence health, such as genetics, exercise, and diet?
All are important, but unlike genetics, the microbiome is as manageable as diet and exercise. It is fundamentally impossible to change one’s genome, but that could become more likely soon. However, we can easily alter a person’s microbiome through diet, for example. Once we know the basic rules, there will be many possibilities. At the moment, they are mostly individual cases, but with a broader scientific basis, much more will be possible.
Do you believe we will eventually be able to examine a person’s microbiome to determine their health risks, similar to the way we now do with gene panels?
Yes, but we will need scientific advances to learn which important biomarkers are relevant in general and for specific people. This will be an area of precision medicine.
Lessons Learned from Decades at the Forefront
You have been involved in this research for over 30 years, primarily focusing on the human microbiome and its role in diseases. When did you realize that this research held unique therapeutic promise?
There has always been the potential from the beginning to use the microbiome to improve human health. In fact, I wrote a perspective on this topic in PNAS in 2010. The key lies in understanding the biology of the microbiome, leading to new preventive measures and new treatments.
At present, there are many „probiotic“ products on the market. Probiotics have a great future, but most have not been thoroughly tested for their efficacy. Were there specific sets of studies that occurred prior to the beginning of the Human Microbiome Project that have led us to the present day?
The studies by Carl Woese in the 1970s and 1980s, using 16S rRNA genes to understand phylogeny and evolution, opened the field of DNA sequencing to consider bacterial evolution and questions of ancestry.
A central theme of your research and the focus of your book are antibiotic-resistant bacteria. What have you learned from this work about describing the science of antibiotic resistance to the broader public?
People do not particularly care about antibiotic resistance. They think it mainly affects other people. In contrast, they do care about their own health and that of their children. The more data shows that the use of antibiotics can be harmful under certain circumstances, the more the use will decline. We need more transparency about benefits and costs.
Are there common misconceptions about the microbiome that you hear from the general public or even from physicians, that you would like to see dispelled through greater efforts?
The public and medical professionals are in love with probiotics and spend tens of millions of dollars on them. However, as mentioned before, they are very diverse and mostly untested for efficacy. The next step would be to test specific formulations to see which ones work for whom and which do not. That would be a great advancement.