“Over the past few years, the microbial world’s reputation has been turned on its head. Since Louis Pasteur proved the so-called germ theory of disease almost 150 years ago, we humans have diligently tried to purge bacteria from our lives. But scientists today are telling us at that the story isn’t so simple, and that the bacteria that colonize our bodies – more than one hundred trillion of them – are actually our coevolutionary partners, crucial to maintaining human health.

Sarkis Mazmanian, PhD, a microbiologist at the California Institute of Technology (Caltech) in Los Angeles, was among the first to foray into the gut microbiome and its links to disease. His research in the last decade has begun to define just how our microbial squatters keep our immune systems healthy – and how a skew in their population may be linked to diseases as diverse as inflammatory bowel disease, multiple sclerosis and autism. Among numerous other awards, in 2011 he received the Burroughs Wellcome Fund’s Investigators in the Pathogenesis of Infectious Disease award. In 2012, his work was honored with a MacArthur Foundation “genius” grant.” (Source)

The following has been paraphrased from an interview with Prof. Sarkis Mazmanian on April 12th, 2018.

(Click here for the full audio version)

How much progress have we made in understanding the link between our gut microbiome and neurodegeneration?

The field is still relatively young, but it has gained a lot of attention and momentum of late. This has been supported by the emergence of new technologies, especially advances in genomic sequencing and bioinformatics. We are now at a stage in the field where we can look into the basic biology of the microbiome and start asking questions about how it relates to diets, diseases, lifestyles and populations.

The connection to neurodegeneration is in its infancy. We have a few flashbulbs that have gone off in the dark, but we are far from having a clear picture. Our laboratory was one of the first to link Parkinson’s disease to the microbiome. This has gotten a lot of popular press, some of which has been hype and I worry about that long term because it makes promises to society that we don’t know yet if we can keep.

We are interested in learning whether the microbiome tells us anything that we can use to treat neurodegenerative conditions, and also to understand the causes of disease. I am hopeful that future research advances may result in ways to improve the health of people suffering from neurodegeneration.

What is your take on claims made that certain probiotics or gut cleaning solutions can help people with Parkinson’s disease?

The knowledge just isn’t there to know what approach will be effective, there is no science behind most commercially available products. We understand so little about the biology of disease, let alone its connection to the microbiome, that anyone who tells you that they have evidence suggesting that they can target the microbiome to help treat any neurodegenerative condition, is guesswork at best.

However, probiotics that are sold commercially are generally safe, so there isn’t much harm being done. But long-term these approaches may not be viable and we need more evidence-based probiotics to validate the link between the microbiome and neurodegeneration.

Have we identified any bacteria that strongly correlate with PD?

There are certainly groups of bacteria that are associated with people with PD, and there are a number of papers now showing that there are microbiome changes in people with PD, but there is very little agreement regarding the details. There are certain types of bacteria that seem to be more prevalent in PD populations, but they are not universally validated and none of them have been shown in humans to actually contribute to the symptoms of the disease. Association studies are powerful, but it doesn’t give insight into cause-and-effect relationships. For example, many PD patients experience constipation, maybe that is reshaping the microbiome in a way that fosters the growth of certain bacteria. So, it could be PD impacting the microbiome rather than the microbiome impacting PD. However, our laboratory has shown that transplanting gut bacteria from PD patients into mice causes motor symptoms compared to transplanting human bacteria from control subjects, suggesting the changes in the PD microbiome contribute to symptoms. This strongly suggests that “treating” the microbiome may have therapeutic benefits for PD patients.

You’ve shown that Alpha-Synuclein travels up through the gut, does that confirm the Braak staging theory?

In animal models there are outcomes that are consistent with Braak’s hypothesis, but it does not validate or confirm it. Again, we are just scratching the surface of what is known about this connection. Also, all of our studies to date that we have performed is in animal models, and thus need to be extended to people. But, generally, the data indicates that it is plausible that PD may initiate in the gut.

Your lab discovered that the microbiome plays a pivotal role in shaping our immune systems, would any therapies that target the gut then be considered immunotherapy?

It could, but again, a lot of research still needs to be done. The idea that the immune system is integral to PD is new. I would put any immunological approach to treat PD in the same bucket as therapies targeting the microbiome. I don’t think anyone would propose immunotherapy for PD yet, but we are examining the immune response in PD because that might give us a clue to understanding the disease.

Do you believe there is too much hype surrounding genomics and genome-wide association studies?

I think they have some short comings, but even our work in the microbiome has been based on genomics. However, neither genetics nor the environment will tell you everything you need to know about the disease, or by themselves lead to therapeutic approaches. I believe we need to understand both the role of the genome and the environment to fully understand PD.

A large number of people still believe that genetics will answer a lot of questions about mankind and disease, but that hasn’t proven to be entirely true. In 2001 the first draft of a human genome was published, the hype that I experienced as a young graduate student at that time was that understanding the genome was going to lead to a revolution in therapies for diseases. I would argue that 17 years later we are incrementally closer to that goal, but still very far away. It is a history lesson, people gravitate towards genetics because it is easier to measure than life exposure and the environment, but it doesn’t tell you everything you need to know about a disease process. You have to look at all facets and how they integrate and lead to a symptom or diagnosis.

You’ve shown that we are symbiotically linked to our microbiome, how has that understanding informed your perception of who you are?

I know we are not alone, on a biochemical level I am as much microbial as I am human. I do on a daily basis think about what is good for microbiome, as much as I think about what is good for me, because the two are inextricably intertwined.

Do you ever stop to think about which decisions that you make are influenced by your microbiome?

The influence that microbes have on behavior and cognition is blurry, I don’t think your microbiome can make you think or feel something, it is more like a modifier. A thought that goes through my brain may have originated from my mind, but the degree to which I act on that thought may be modified by my microbiome. But, I don’t think the microbiome is controlling the actual thought.

This is all speculative, but as a hypothetical example let’s say someone honked at me while I’m driving. If I am having a good day because my microbiome is properly balanced, then I may just ignore them. They may have elicited a primal anger response in me, but my microbiome modified that response because it is part of the reason why I am generally in a pleasant mood. However, if I ate something that upset my microbiome, I might be more likely to turn around and say something to the person that honked.

Where do you think this field will be in 10-20 years?

I’m really interested in disease related biomedical research. So from that perspective, I am hopeful that we will learn enough about the microbiome and ourselves to figure out ways of leveraging the microbiome to improve quality of life. As an academic, I thrive on intellectual curiosity, I want to figure out how stuff works, and a byproduct of that is imparting knowledge on society. But, if I can leverage that knowledge to help people, that would be even more gratifying.

I think it is practically achievable. Look at the genome, we have had tremendous advances in gene editing and gene therapies that have a tremendous amount of potential, but improving our genome is still very challenging as I mentioned earlier. However, the microbiome is an easier target because it is more straightforward to replace and control bacteria in the gut than to change our genome. Many aspects of life are a result of a combination of our genetics and our environments, they are inseparable, that is how we evolved. If we want to fine tune these outcomes, the microbiome is just lower hanging fruit, so it makes more sense to target it first. That is what I am hoping to achieve through the work that we are doing.

Click here to learn more about the work of Prof. Sarkis Mazmanian or watch this video below to learn more about the gut-brain axis.