Tuesday, August 29, 2017

We Must All Be Healthy Together...

Is there anything our microbiome can't do?

We're starting to get a better picture of how our microbiome impacts our health, and I'll get to that shortly, but at the recent Biohack the Planet conference some clever folks at Biota Beats figured out how to turn the microbiome into music:    

Click here to check out what it actually sounds like (especially the full symphony).  

OK, so it's not Beethoven or even Jay-Z (although David Sun Kong, an MIT biologist who presented the work, says DJ Jazzy Jeff is going to put a track from his microbiome on his next record), but it is pretty cool.  

Imagine that one day we might diagnose our health by checking the sounds of our microbiome.

For anyone who hasn't been paying attention, the microbiome are all the microbial organisms living in, on, and around us.  They are literally everywhere, and their genes outnumber our genes by 100-to-1, perhaps more.  They even have more cells than we do.  

That probably sounds terrible to many people.  We're a nation that demands antibiotics at the slightest sniffle, that puts antibiotics in its food chain, that uses antibiotic soaps.   Ever since we discovered penicillin, we've decided that if we can kill off "foreign" invaders to our bodies, we should.

And, certainly, much good has come from that.  We don't usually die of infections any more.  The trick, though, is understanding what is "foreign," and what is "invading" us, rather than simply at home in us.   

We start acquiring our microbiome in the birth canal (and, in fact, if you came out via a Cesarean-section, it can adversely impact your microbiome), and its composition is constantly changing from then on.  Children eating dirt, for example, is generally frowned upon by modern parents, but it is actually is a great way for them to boost their microbiome.  There is a "hygiene hypothesis" that links increasing incidence of autoimmune and allergic diseases to our efforts to avoid such "germs."

The Human Microbiome Project has been studying our microbiomes since 2008, and, as with our own genome, it seems that the more we learn, the more we realize how much more there is to learn.  Links between our microbiome and our health seem to be everywhere we look.  

The microbiome is deservedly becoming a big research focus.  Indeed, the Cleveland Clinic listed microbiome as the top medical innovation of 2017:

IBM, Harvard, MIT, Mass Gen, UCSD and the Flatiron Institute are teaming up to map 3 million genes found in the gut microbome (you can donate spare computing time in the effort).   This is only one of several efforts in the field, TechCrunch reports.   

It has been well documented that our gut microbiome not only helps us digest foods, but also how we store fat, gain weight, regulate blood glucose, even what food we crave (e.g., chocolate!).  The following chart illustrates the complex interactions:
Boulange, et. al.
Researchers Jasenka Zubcevic and Christopher Martyniuk assert that: "There’s growing evidence of a link between the brain and our microbiota as well."  Their research found that the brain communicates with the gut microbiome via the bone marrow immune cells, which suggests connections to our immune responses and immune diseases.

In addition, the gut microbiome has been linked to stress, anxiety, and other mental health issues.  Which, as Professors Zubcevic and Martyniuk put it, gives "a whole new meaning to the term 'gut feeling.'"

And we're still being surprised.  A new study of the Hadza, an African hunter-gatherer tribe, found that their microbiome varied seasonally, possibly based on changing diet throughout the year.  The degree of the changes were unexpected, with some of the microbiota dying off entirely, then reemerging.  

Their microbiome was also dissimilar to those found in more industrialized societies.  As to why, or what it meant for our health, the researchers could only say: "That’s a huge question — it’s the elephant in the room." 

Justin Sonnenburg, the lead author of the Hadza study, admitted to The New York Times, "We don’t have a good grasp of what these seasonally varying microbes even do."
Two 2016 studies tried to correlate a host of factors with people's microbiome, and could only explain 8-16% of the variation.  As one of the researchers said, "It's very humbling."

Two researchers -- Rebecca Vega Thurber and Jesse Zaneveld -- have proposed what they call the Grand Unification Theory of Unhealthy Microbiomes,  It theorizes that when microbiomes become unhealthy, they do so in unpredictable ways.  They become more varied, but in every direction.  

That's why Dr. Zanesveld likes to call it the "Anna Karenina" hypothesis, as in, Tolstoy's famous opening: "All happy families are alike; each unhappy family is unhappy in its own way."

The theory is still in the early stages, but it is drawing attention.  The fact that our microbiomes vary both from each other's and over time even when healthy complicates our understanding of when it is not.  As The Atlantic's Ed Yong points out,  "if the microbiome is ruled by randomness, then it might be hard to determine whether a particular community is unhealthy, and to develop standardized, effective ways of steering it back on course."

We're proud of 21st century approaches to medicine like breakthroughs in immunotherapy or gene therapy, but, in some ways, we're still like when we started understanding the role of bacteria and viruses.  Dr. Sonnenburg concluded: "We have to think of ourselves as these composite organisms, with microbial and human parts."  

Professors Zubcevic and Martyniuk came to a similar conclusion, especially as we increasingly rely on pharmacological interventions that may impact the microbiome:  
Much like the chicken-or-the-egg scenario, however, this complex interplay warrants further investigation to fully understand the consequences (or benefits) of perturbing one single component of the gut microbiota.
The fundamental change to thinking about our health that we have to make is that, when it comes to our microbiome, it isn't "us" versus "them."

It's all us.

When he was urging his fellow citizens towards independence, Benjamin Franklin famously said, "we must, indeed, hang together or, most assuredly, we shall all hang separately."  So it is with our health and the health of our microbiome.  We're in this together.

Meanwhile, I'm looking forward to hearing my microbiome!

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