Microbiomes R Us -- another form of science marketing

The microbiome hits the big time 
A piece by food writer/journalist Michael Pollan, "Some of My Best Friends Are Germs", was the cover story of the New York Times magazine on Sunday.  Pollan says the interest he developed in fermented foods while he was writing his latest book -- beer, kimchi, cheeses -- naturally led into an interest in the fermentation that goes on in our large intestines with the help of resident microbes, and this led him to think generally about the interaction between microbes and us.

The current estimate is that microbial cells in and on our body outnumber our own cells ten to one.  The Human Microbiome Project, funded by the NIH, as yet another Big Science do it all and think about it later investment, was launched in 2008 with the goal of sequencing the microbes in the nasal passages, oral cavities, skin, and the gastrointestinal and urogenital tracts of a fairly small sample of men and women.  The project was completed last spring with sequences from samples from more than 240 people (completed means the authors can now go to the press and demand even more money because 'more research is needed' before we understand anything.....).

But, that's not the end.  In a drive to document the microbiome of America, The American Gut Project will sequence your microbiomes for $99.  It's an open source, open access project which allows participants to compare their data with data from people around the world. 

Why?  Because the microbiome is the new genetics.  Forget (our own) genes, the idea is that we are who we are, healthy or sick, because of the microbes we share our bodies with. Well, of course, it's the microbes' genes, so it's really just more genetics.  As Pollan puts it,

To the extent that we are bearers of genetic information, more than 99 percent of it is microbial. And it appears increasingly likely that this “second genome,” as it is sometimes called, exerts an influence on our health as great and possibly even greater than the genes we inherit from our parents.

Our microbiome may make us fat or keep us thin, predispose us to diabetes or heart disease or asthma and allergy. And, the microbiome apparently influences our immune system and trains it in how it responds to the world, and may be responsible for the increase in autoimmune diseases in the West. Indeed, Pollan writes of "an impoverished 'Westernized microbiome'" -- some researchers suggest that the microbiota in our gut should be restored to look more like the microbiomes of people who eat less processed food and take fewer antibiotics (and, by the way, are more likely to die early of infectious diseases than we are). 

But, happily for us, changing our second genome is going to be a lot easier than changing our first one.  We do it all the time, through our diet, the medicines we take, the people (and their microbes) we come into contact with.  Happily for Big Pharma and Big Food, once we know which microbes are best for us, they'll be able to sell you any number of products to reverse these changes and reduce your chances of getting all those diseases geneticists have been trying to find the causes of for so long.  You'll have personalized microbiomalgenomic medicine.  Enough to put another smile on Francis Collins' funds-securing face!

There has been a lot of talk lately about 'fecal transplants' which are just what they sound like -- the transfer of fecal bacteria from healthy people into the colons of unhealthy people, primarily people with Clostridium difficile infections, intestinal infections resistant to antibiotics.  And yes, there is a lot of information on the web for those who want to learn to do this kind of self-medicating at home.  

Overpromising yet?
Pollan (whose qualifcation for writing this piece is that he is a food journalist whose writing sells well) says a few times that people involved in researching the microbiome don't want to make the same mistake that geneticists did with the Human Genome Project, overpromising the extent to which their work will lead to the cure for everything that ails us.  But, if as Pollan claims, the microbiome community is actually talking about the Grand Unified Theory of Chronic Disease, there's apparently a fine line between hype and overpromising -- not to mention borrowing from physics' line that is used to justify Hadron.  And there are certainly plenty of 'probiotic' options in the grocery store these days, so someone's jumping the bandwagon. 

All satire aside, the point isn't that we doubt that there's a connection between microbes, health and disease.  Nor that there are indeed lots of nuggets of grain in the bin being described.  Instead, it's that these are early days yet, and the whole approach to this project is already sounding too reductionist for words.  Not only are microbiome researchers in danger of mimicking the genome project with overpromising to over-enumerate, but also by reducing everything to their favorite microbe (for 'microbe' we used to read 'gene'). The bugs for ability to play the bass or baseball, score well on IQ tests, or tolerate abuse with equanimity may be right around the corner.

Enough Just-So stories yet?
Indeed, the Just-So storytellers are already out in full force. Why are there complex carbohydrates in human breast milk, if babies can't digest them?  As Pollan puts it, "Evolutionary theory argues that every component of mother's milk should have some value to the developing baby or natural selection would have long ago discarded it as a waste of the mother's precious resources." So, it turns out they are there for a particular gut bacterium that breaks them down and uses them.  

“Mother’s milk, being the only mammalian food shaped by natural selection, is the Rosetta stone for all food,” says Bruce German, a food scientist at the University of California, Davis, who researches milk. “And what it’s telling us is that when natural selection creates a food, it is concerned not just with feeding the child but the child’s gut bugs too.”

And, we evolved this commensurate relationship with microbes because they evolve so much faster than we do, so can quickly evolve mechanisms to cope with new kinds of toxins in our environment and so forth.

And, the bacterium that causes ulcers and perhaps some stomach cancers, Helicobacter pylori, is an endangered species, writes Pollan.  But his informants tell him it shouldn't be.  H. pylori also has beneficial roles to play in our stomachs -- preventing acid reflux by regulating acidity, for example, which Pollan suggests they do to render the stomach inhospitable to competing microbes, or regulating levels of an appetite hormone -- and because they do these good things, they should be nurtured rather than killed off.  Why do they do both good and bad?  Well, they do the bad stuff when we're middle-aged or older, so Pollan's informant suggests "this microbe’s evolutionary role might be to help shuffle us off life’s stage once our childbearing years have passed."

Of course, among other curious aspects of this scenario, how something evolved to kill us off once we're no longer contributing genes to the human gene pool is not explained. In order for this to work, the fitness of the microbe that could do this would have to be increased by killing us, its host, and it doesn't work that way.

Stripping it down to the truth
Again, fine, it seems quite likely that our microbiome does make contributions to our health and disease.  That's interesting enough.  For various theoretical reasons, rapidly dividing microbes do present interesting evolutionary challenges, and there's no doubt that we, and our genomes, must respond successfully if we are to persist.  If infection, broadly defined, has early negative effects because of the host's genotype, then selection favoring the bacteria, and likewise selection favoring human resistance can both be strong.  Culture and climate and habits also contribute to this potentially very dynamic evolutionary mix.  Infectious diseases with strong effect on survival, like malaria and HIV and others have clearly demonstrable effects of this kind.

But that is not the same as invoking specific selective stories for complex, ephemeral, varying fluxes of bacteria, which must coexist as well as keep a host alive so they can stay alive.  It's not the same as inventing pat, closed Just-So stories about how this or that effect must have evolved, and it involves no subtleties that we know are applicable, including the range and mobility of humans, modes of transmission,  population size and so on.  We have had a difficult time, and often unsuccessful, in working out clear-cut examples of natural selection at work in humans, though our evolved defenses against malaria (which is not caused by bacteria but involve many relevant evolutionary issues) may be the best one. 

So why can't researchers, writers, the rest of us just concentrate on figuring out how and when microbes are harmful or beneficial, without the hyperbole, the suggestion that microbes now do everything that genes did not long ago, and the made-up stories about how this all evolved? 

This whole microbiome thing needs to slow down and let the science catch up.