Human microbiome research has progressed in leaps and bounds over the past decades, from pivotal studies begun in the 1970s to the launch of the Human Microbiome Project in 2007. Breakthroughs have laid the groundwork for more recent clinical applications, such as fecal microbiota transplantation (FMT), and advanced techniques to explore new therapeutic pathways. Yet the "microbiome revolution" is just getting started, according to professor Martin J. Blaser, MD, one of the field's pioneers.
The ongoing research and clinical trials into the microbiome's link to the major causes of death in the United States hold the promise of interventions that manipulate the microbiome to prevent, slow, or perhaps even cure these conditions, says Blaser, who holds the Henry Rutgers Chair of the Human Microbiome and is director of the Center for Advanced Biotechnology and Medicine at Rutgers University in New Brunswick, New Jersey.
Blaser is the author of Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, serves as chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria and is a member of the scientific advisory board of the biotech startup Micronoma.
In this interview, which has been condensed and edited for clarity, Blaser discusses where we're at now and where he sees the microbiome field evolving in the coming years.
Highlighting the Most Promising Applications
Which recent studies on the link between the human microbiome and disease have you found particularly promising?
There have been a number of studies, including our own, focusing on the gut-kidney axis. The gut microbiome produces, or detoxifies, metabolites that are toxic to the kidney: for example, those involved in the formation of kidney stones and in the worsening of uremia.
Altering the microbiome to reduce the uremic toxins and the nidus for stone formation is a very promising field of research.
What other disease states may be amenable to microbiome-based interventions?
There are diseases that are caused by known genetic mutations. Yet, for nearly all of them, there is great variation in clinical outcomes, which might be classed as genes multiplied by environment interactions.
It seems likely to me that microbiome variation could account for some proportion of those differences for some genetic diseases.
It's now well established that altering the microbiome with FMT is a successful intervention for recurrent Clostridioides difficile infections. What do you see as the next disease states where FMT could prove successful?
If you go to ClinicalTrials.gov, you will find that that there are 471 trials registered using FMT. This is across a broad range of illnesses, including metabolic, immunological, autoimmune, inflammatory, degenerative, and neoplastic diseases.
Which will be the next condition showing marked efficacy is anyone's guess. That is why we must do clinical trials to assess what works and what does not, regardless of specific illness.
The donor's microbiome appears to be vital to engraftment success, with "superdonors" even being identified. What factors do you think primarily influence microbiome engraftment?
There is an emerging science about this question, driven in part by classical ecological theory.
Right now, we are using FMT as if one size fits all. But this probably would not provide optimal treatment for all. Just as we type blood donors and recipients before the blood transfusion, one could easily imagine a parallel kind of procedure.
Are there any diseases where it's just too far-fetched to think altering the microbiome could make a difference?
The link between the microbiome and human health is so pervasive that there are few conditions that are out of the realm of possibility. It really is a frontier.
Not that the microbiome causes everything, but by understanding and manipulating the microbiome, we could at least palliate, or slow down, particular pathologic processes.
For all the major causes of death in the United States — cardiovascular disease, cancer, dementia and neurogenerative diseases, diabetes, and lung, liver, and kidney diseases — there is ongoing investigation of the microbiome. A greater promise would be to prevent or cure these illnesses.
Predicting the Next Stages of the 'Microbiome Revolution'
Do you believe we are at a turning point with the microbiome in terms of being able to manipulate or engineer it?
The microbiome is a scientific frontier that has an impact across the biosphere. It is a broad frontier involving human and veterinary medicine, agriculture, and the environment. Knowledge is increasing incrementally, as expected.
Are we at the point yet where doctors should be incorporating microbiome-related lifestyle changes for people with or at risk for cancer, heart disease, Alzheimer's disease, or other chronic conditions?
Although we are still in the early stages of the "microbiome revolution," which I first wrote about in EMBO Reports in 2006 and then again in the Journal of Clinical Investigation in 2014, I think important advances for all of these conditions are coming our way in the next 5-10 years.
How are prebiotics, probiotics, and postbiotics being used to shape the microbiome?
This is a very important and active area in clinical investigation, which needs to be ramped up.
Tens of millions of people are using probiotics and prebiotics every day for vague indications, and which have only infrequently been tested in robust clinical trials. So, there is a disconnect between what's being claimed with the bulk of the probiotics at present and what we'll actually know in the future.
How do you think the microbiome will stack up to other factors influencing health, such as genetics, exercise, and nutrition?
All are important, but unlike genetics, the microbiome is tractable, like diet and exercise.
It is essentially impossible to change one's genome, but that might become more likely before too long. However, we can easily change someone's microbiome through dietary means, for example. Once we know the ground rules, there will be many options. Right now, it is mostly one-offs, but as the scientific basis broadens, much more will be possible.
In the future, do you think we'll be able to look at a person's microbiome and tell what his or her risk of developing disease is, similar to the way we use gene panels now?
Yes, but we will need scientific advances to teach us what are the important biomarkers in general and in particular people. This will be one area of precision medicine.
Lessons From Decades at the Forefront
You've been involved in this research for over 30 years, and the majority has focused on the human microbiome and its role in disease. When did it become apparent to you that this research had unique therapeutic promise?
From the very start, there was always the potential to harness the microbiome to improve human health. In fact, I wrote a perspective in PNAS on that theme in 2010.
The key is to understand the biology of the microbiome, and from the scientific study comes new preventives and new treatments. Right now, there are many "probiotic" products on the market. Probiotics have a great future, but most of what is out there has not been rigorously tested for effectiveness.
Was there a particular series of studies that occurred before the launch of the Human Microbiome Project and brought us to the current era?
The studies in the 1970s-1980s by Carl Woese using 16S rRNA genes to understand phylogeny and evolution opened up the field of DNA sequencing to consider bacterial evolution and issues of ancestry.
A key subject of your research and the focus of your book is antibiotic-resistant bacteria. What did this work teach you about describing the science of antibiotic resistance to the general public?
People don't care very much about antibiotic resistance. They think that affects other people, mostly. In contrast, they care about their own health and their children's health.
The more that the data show that using antibiotics can be harmful to health in some circumstances, the more that use will diminish. We need more transparency about benefits and costs.
Are there any common misconceptions about the microbiome that you hear from the general public, or even clinicians, that you would like to see greater efforts to dispel?
The public and the medical profession are in love with probiotics, buying them by the tens of millions. But as stated before, they are very diverse and mostly untested for efficacy.
The next step is to test specific formulations to see which ones work, and for whom, and which ones don't. That would be a big advance.
John Watson is a freelance writer in Philadelphia, Pennsylvania.
Comments