Self & Other
18. The Microbiome Decade
In January 2013, the New England Journal of Medicine published a clinical trial that had been stopped early. This is unusual and almost always for one of two reasons. Either the treatment being tested is causing serious harm, in which case stopping is ethically required. Or the treatment is working so much better than the comparison that it would be unethical to keep giving the comparison treatment to half the patients in the study.
This was the second case.
The trial, run by a Dutch research group led by Els van Nood, was treating patients with recurrent infections of a bacterium called Clostridioides difficile, often abbreviated C. diff. C. diff is a problem mostly of hospitals and nursing homes. It typically takes hold after a course of antibiotics has wiped out the protective bacteria of the gut, leaving the colon’s surface free for C. diff to colonize. The bacterium produces toxins that cause severe, sometimes life-threatening diarrhea. The standard treatment, ironically, is more antibiotics — specifically, vancomycin — which works the first time in most cases but often fails in patients who have relapsed multiple times. For those patients, with C. diff that keeps coming back after every course of antibiotics, the prognosis can be grim. Some die.
The Dutch researchers were testing an alternative. Instead of more antibiotics, they were taking stool samples from healthy donors, processing them carefully, and infusing the resulting bacterial slurry into the patients’ upper intestines through a thin tube. The procedure had a name that everyone tried not to say at dinner parties: fecal microbiota transplant. The idea was that transplanting an entire functional microbial community from a healthy person could re-establish the protective bacteria that the antibiotics had destroyed, crowding out C. diff and restoring the colon to a state in which it could defend itself.
The patients in the standard-treatment arm — vancomycin alone — had their infection cured about thirty percent of the time. The patients who received the fecal transplant had their infection cured more than ninety percent of the time. The difference was so large, and the disease so serious, that the trial’s safety monitoring board concluded that continuing was ethically untenable. The fecal transplant arm was, by any reasonable measure, a different category of intervention. The trial was stopped. The remaining patients in the trial were offered the transplant.
This trial, published in one of the most prestigious medical journals in the world, did something that the microbiome field had been trying to do for years. It demonstrated, with high-quality randomized evidence, that manipulating the bacterial communities of the gut could cure a real disease that nothing else reliably could. The community of resident microbes was not a metaphor. It was a functional organ, and giving someone a healthy version of it could heal them.
This is the chapter where we look back on the decade that followed — a decade in which microbiome research went from a small specialty to one of the largest and most overhyped areas of biology — and try to sort out what was actually established and what was sold to us in podcasts.
What We Actually Know
Some statements about the gut microbiome are now well-established enough that you can build on them. The list is shorter than the popular literature suggests, but it is real.
The microbiome is a community, not a fixed inventory. The composition of bacteria in any individual gut shifts based on diet, antibiotic exposure, illness, age, and a long list of other factors. There is no single “ideal” microbiome that everyone should aim for. The communities of healthy people are quite different from each other, and what counts as healthy seems to be more about overall diversity and certain functional capabilities than about any specific list of bacteria.
Antibiotics disrupt the microbiome in measurable, sometimes durable ways. A course of antibiotics can shift the community composition for weeks to months, and certain antibiotics can produce changes that persist for years. This is not, by itself, a reason to refuse necessary antibiotics — the diseases they treat are often life-threatening, and the alternative is much worse — but it is a reason to take antibiotics when they are needed and not for things they cannot help, such as viral infections.
Diet shapes the microbiome rapidly. Within days of changing what you eat — from a typical Western diet to one heavy in plant fiber, for instance, or vice versa — the dominant bacterial populations in the gut shift in measurable ways. The shift is reversible. The microbiome is, in this respect, a fast-responding system that takes its cues from what is currently passing through.
The microbiome contributes to the function of the immune system, the metabolism, and probably several other systems we are still figuring out. The mechanisms are increasingly well-mapped: short-chain fatty acids produced by bacterial fermentation of fiber affect the gut wall, the regulatory T cells we met in Chapter 7, and probably several systemic processes. Bacterial metabolites enter the bloodstream and reach distant organs. The community of microbes is, in a real and quantifiable sense, part of the body, even though none of its cells share your DNA.
These statements are well-supported. They are also, you may notice, fairly modest. They do not say that any specific bacterium causes any specific disease, that any particular probiotic product will give you a particular outcome, or that any single dietary intervention will transform your gut. The careful version of microbiome science is more limited and more honest than the version on the supplement shelf.