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It’s no surprise that most people don’t feel great at the gym when they’re taking antibiotics. After all, if you’re taking them, that generally means that you’re either ill or just getting over an illness. But lately there’s been a surge of scientific interest in the idea of a gut-muscle axis, which posits that the microbes in your intestines are affected by physical activity and, in turn, affect your ability to perform physical activity. That raises an interesting question: do antibiotics, which wipe out large swaths of your gut flora, have a direct effect on athletic performance?
There have been a bunch of studies supporting the idea of a two-way gut-muscle axis, mostly in mice. Transplanting fecal bacteria from unusually healthy older humans into mice makes them stronger. Eliminating gut bacteria in mice with a wide-spectrum antibiotic reduces running endurance. Most prominently, in 2019, a lactate-eating bacteria found in the poop of Boston marathoners made mice faster. But when you move past the headlines, the actual research remains confusing and contradictory: every study seems to find a different magic microbe.
The good news, then: two new studies on the effects of antibiotics on exercise reach similar conclusions. There are still plenty of caveats—both studies are in mice, for one thing. But they suggest an interesting twist: the biggest athletic effect of antibiotics may be on the brain, not the muscles.
The first study, led by Monica McNamara and Theodore Garland of the University of California, Riverside and published in Behavioural Processes, compared two different types of mice. One was the famous High Runner line. Back in 1993, researchers began selecting mice who showed unusually high levels of voluntary wheel running and breeding them with each other. The mice in the UC Riverside study are from the 89th generation of this program, and they now choose to run about three times as much daily as mice from the control group, who come from the same original group of mice but weren’t selectively bred for running.
After two weeks of baseline wheel-running, the mice were put on broad-spectrum antibiotics (meaning they wiped out most gut bacteria rather than just certain strains) for ten days. Here’s what their average “running log” looked like, measured in revolutions of the wheels in their cages:
The daily distance drops by 21 percent in the High Runner mice, and doesn’t return to normal during the subsequent 12 days. In the control mice, on the other hand, nothing seems to change. Neither group showed any evidence of being sick: their weight and food consumption were unaffected. This suggests that some part of whatever it is that’s been bred into the High Runner mice is affected by antibiotics.
One possibility is that this is a gut-muscle axis effect. The High Runner mice have some sort of microbial advantage—something like the lactate-eating microbe from Boston marathoners—that makes running physically easier for them, which is why they run so much. Take that edge away, and running isn’t as much fun, so they do less of it.
The other possibility is that it’s the gut-brain axis in action. McNamara cites some previous research showing that the gut microbiome can influence motivation and reward circuitry in the brain: antibiotics affect how certain amino acids are absorbed from the gut into the bloodstream, after which they travel to the brain where they’re transformed into brain chemicals such as dopamine and serotonin. McNamara’s experiment can’t distinguish between these two possibilities, but either way the motivation to exercise seems to be blunted.
The second study, led by Noah Hutchinson and Jeffrey Woods of the University of Illinois at Urbana-Champaign and published in Medicine & Science in Sports & Exercise, has a similar setup. They compared normal lab mice with and without broad-spectrum antibiotics, plus a group of “germ-free” mice that were specially bred from birth to have no microbiome at all. In this case, the researchers were interested in how the antibiotics affected training adaptations: after six weeks of voluntary wheel-running, would the antibiotic and germ-free mice gain as much fitness as the control group? Their hypothesis was no.
Once again, voluntary wheel running was reduced in the antibiotic group by 22 percent, and was 26 percent lower in the germ-free group. Here’s what their daily mileage tallies looked like (squares are the control group, circles are on antibiotics, and triangles are germ-free):
But their response to this training tells a slightly different story. In a treadmill test to exhaustion, the antibiotic mice improved similarly to the non-antibiotic mice (their improvement was slightly smaller, but the difference wasn’t statistically significant, and would be expected anyway since they chose to run less during the training period). Moreover, tests of gene expression and muscle properties also found that the antibiotic group fared just as well.
The germ-free mice, on the other hand, didn’t improve as much after the training period. Since the antibiotic group wasn’t affected by its lack of microbiome, this suggests that the germ-free mice had some sort of pre-existing developmental deficit thanks to growing up without a microbiome that compromised their ability to respond to training.
The practical takeaway, according to Hutchinson and his co-authors, is that if you need to go on antibiotics in the lead-up to an important competition, it’s unlikely that it will affect your training adaptations or your performance. I think that’s a reasonable and reassuring position, bearing in mind all the uncertainties inherent in applying mouse studies to human behavior.
But it’s the apparent change in motivation to exercise that really intrigues me. Is there something there that helps explain who among us ends up as a High Runner? If so, can we manipulate it? It’s easy to see how you could get caught up in the excitement around potential new probiotic supplements that alter not just your ability but also your desire to exercise. Garland, in a UC Riverside press release, hints at that possibility. But his advice, for now, is suitably grounded in the current reality. If you want a healthy microbiome, he suggests, you should eat a balanced diet and exercise regularly.
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