Self & Other · The Microbiome Decade
The Hype Machine
The clearest clinical success of microbiome science, to date, is fecal transplant for recurrent C. diff infection. As of the mid-2020s, this is now standard of care in many countries for patients with multiple relapses, and the procedure has been refined into more pleasant forms — capsules of freeze-dried, processed donor material that can be swallowed, rather than the original infusions. Recently, regulated and standardized fecal-derived products have begun to receive FDA approval, formalizing what had been a somewhat improvisational procedure.
A few other clinical applications have shown enough promise to be taken seriously, though most are still being worked out. Certain forms of inflammatory bowel disease may respond to microbiome-modulating therapies in some patients, though the data are mixed and no single approach has yet emerged as clearly effective. Antibiotic-associated diarrhea, both during and after antibiotic courses, can sometimes be reduced by certain specific probiotics, although the evidence is most clear for hospitalized adults receiving high-risk antibiotic regimens, and the products and strains that work are not the ones most people buy at drugstores.
There is also an emerging conversation about the microbiome’s effect on cancer immunotherapy. Several studies have found that patients with certain gut bacterial profiles respond better to checkpoint inhibitors (the cancer drugs we discussed in Chapter 12) than patients with different profiles. Early trials of fecal transplants in patients who have stopped responding to immunotherapy have produced encouraging results. This is a striking finding if it holds up: the bacteria in your gut may modulate how well your T cells work against your cancer somewhere else in your body. The implications, if real, are large. The work is still in progress.
The Hype Machine
Now we have to be honest about the rest.
Beginning around 2010 and accelerating through the decade, microbiome research went through something that happens to most exciting young fields. Sequencing technology became cheap enough that researchers could measure microbiome composition in any group of people and any condition they wanted. The studies multiplied. Almost every disease was, at some point, looked at through a microbiome lens, and almost every disease showed some difference in microbiome composition between affected and unaffected people. The journals filled with associations.
The trouble with associations — and this is the part that almost every popular treatment of the microbiome glosses over — is that they do not, by themselves, tell you which way causation runs. If people with depression have different gut bacteria than people without depression, this could mean that the bacteria contribute to depression, or it could mean that depression (and the diet, sleep, and behavior changes that come with it) shapes the bacteria, or it could mean that some third factor influences both. Distinguishing these possibilities requires intervention studies — studies in which the bacteria are deliberately changed and the disease is then tracked — and intervention studies are much harder to do, much more expensive, and much rarer in the literature.
The decade of explosive microbiome association studies produced thousands of papers. The decade of carefully designed intervention studies produced very few. The popular literature, however, drew freely from the associations and presented them as if they had been mechanistically established. The result is a public discourse in which the gut microbiome has been blamed for, and credited with, almost everything: depression, autism, anxiety, obesity, longevity, intelligence, cancer, athletic performance, the quality of one’s relationships, and the political affiliations of one’s children. Some of these claims have a thread of real science behind them. Most of them are running far ahead of what has been demonstrated.
A few specific examples are worth treating individually.
Some Specific Claims, Sorted
The gut-brain axis and depression. The underlying biology is real. The vagus nerve carries signals between the gut and the brain. Bacterial metabolites enter the bloodstream and can affect brain function. Certain neurotransmitter precursors are produced or modified by gut bacteria. There are mechanistic hypotheses that range from plausible to speculative.
What is overhyped is the leap from these mechanisms to the claim that you can treat depression by adjusting your gut bacteria. The intervention studies in human depression have been, on the whole, disappointing. A few small trials of certain probiotic strains in mild depression have shown small effects. Larger trials in clinical depression have mostly not. The microbiome may turn out to be one of many factors involved in mood disorders, alongside genetics, neurochemistry, life circumstances, and the things that humans have always understood to affect mood. It is not, on the available evidence, a quick fix for any of these things.
The microbiome and obesity. There is genuinely interesting evidence here, including the famous experiments by Jeffrey Gordon’s lab in which microbiome transplants from obese versus lean mice produced different weight outcomes in recipient mice. Bacterial communities clearly affect how efficiently calories are extracted from food and how energy is stored.
What is overhyped is the implication that you can lose weight by manipulating your microbiome through commercial products. Human studies of microbiome-based weight-loss interventions have generally produced small or null effects. The mouse studies have not translated cleanly. The microbiome may be a part of how human metabolism works — we know it is — but it is not a leverage point that consumer products have yet figured out how to manipulate effectively. The interventions that work for sustained weight management remain the slow ones: dietary patterns over years, regular movement, and, for some people, the new generation of GLP-1 receptor agonist medications, which work on a different system entirely.