Posted by Whenever a new discipline, especially one using a ‘sexy’ technology, is brought to bear on human disease, it seems to be oversold in what it will actually accomplish. In addition, every problem is suddenly viewed through that lens, that if we understand how phenomenon X influences something, then WE CAN HAZ CUREZ. I’m worried that this is happening to the human microbiome, the study of the microbes that live in and on us (Note: I’m going to call this area of study ‘the human microbiome’ since a term like metagenomics doesn’t include classical microbiological techniques; calling it the Human Microbiome Project also seems inaccurate, since that’s a funded NIH initiative, not a field*).
For the record, I’ve been involved heavily in NIH’s Human Microbiome Project (HMP) for most of its existence. So I’m not approaching this as an outsider or as someone who pissed that studying the human microbiome is STEALING ALL TEH FUNDZ. I think the HMP is worthwhile. Also, it’s obvious that some diseases are associated with changes in the microbial fauna (I just heard a very good talk last week describing how cystic fibrosis exacerbations and colorectal cancer are associated with microbial community changes). There’s a lot of data indicating that Crohn’s Disease and other similar illness are also correlated with changes in the microbiome. Note that I said associated. A lot more work needs to be done to determine if there causal links. The community changes could simply be a result of the disease.
So there’s a role. But what I’ve noticed looking at various datasets is that, as we move away from severe disease towards ‘normal’ human variation (e.g., overweight or mildly obese people), there doesn’t seem to be strong associations.
In fact, my take on it (and I have to be vague intentionally) is that the microbiome is pretty variable among different ‘healthy’** people, and isn’t well correlated with many traits. Keep in mind that many of the early studies had really small sample sizes and haven’t been replicated and where they have the results are conflicting (Got Decline Effect?). Yet I still see a lot of claims (more in the popular press, but also by researchers) that we’ll be able to keep your weight under control by changing your microbiome, or that your hormones could be affected by your microbiome without much (or any) experimental data to back it up (and, no, if you’ve shown A, while B, C, D and so on could follow–and is fun to speculate about–it doesn’t mean they will). Then we speculate further by pondering whether we can understand what it means to be human without understanding our microbes (in a trivial sense, no).
This, I think, stems from a piss poor metaphor about the human microbiome. It’s de rigueur to begin a microbiome talk by stating that ninety percent of the cells in the human body are bacterial. Then there’s a statement about how we should regard these microbes as another organ, like your heart or liver. And that’s where things go off the rails.
The microbiome is not an organ. Those critters are not your ‘friends.’ They’re not necessarily your ‘enemies’ either, but many of them function like a protection racket–get rid of them, and really bad news moves in. There’s a reason why farmers want to give subtherapeutic levels of antibiotics to their animals to make them grow larger–those drugs are killing or inhibiting something that is decreasing the host’s growth***.
I would argue instead that we have co-evolved to be in homeostasis with our microbiome. If we didn’t our phenotype (e.g., weight, hormone levels, etc.) would fluctuate wildly, since a person’s microbiome fluctuates wildly from day to day. In other words, we have evolved to dampen the effects of the microbiome’s inherent variability on our bodies. When most reasonably healthy people have different microbiomes from each other and differ widely in the same person at different times, that might be telling you something important.
I don’t want to set up a strawman here: there probably are some correlations between ‘normal’ human variability and microbial variation, although my current take on the data is that they’re pretty weak. And, as I noted at the outset, diseases that can only be described as a massive breakdown of health are associated with microbiological changes–and we need to understand those changes, even if they’re only diagnostic, not causal. But we shouldn’t overstate the case either. That’s not helping.
*We should be calling it human microbial ecology or something like that.
**Defining a healthy person is really difficult. I’m using the pornographic definition of health: I know it when I see it. Cuz this is a blog, not a paper.
***I’m not arguing for antibiotics in animal feeds by the way. Antibiotic resistance ain’t cool. But it does cast doubt on the ‘helpful’ microbiome perspective.
March 29, 2011
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