Without Healthy Guts, The Social Brain Regions Of Mice Don't Develop Properly

Antibiotics interfere with the development of the areas of the mouse brain that control sociability, and may do the same for humans. unoL/Shutterstock

Large doses of antibiotics interfere with the development of areas of the mouse brain important for social interactions, probably by wiping out gut bacteria. Although the effect has not been demonstrated in humans – and would be very hard to test ethically – there is some evidence the inhabitants of our digestive system help form our own brains.

Mice raised without a gut microbiome or given antibiotics when young have been observed to be less likely to interact with other mice and show cognitive deficits, Dr Katerina Johnson of Oxford University told IFLScience. In studying why, Johnson discovered that three important signaling pathways were affected in these mice's frontal cortexes. The frontal cortex controls much of mammalian social interactions, as well as mood and personality.

In BMC Neuroscience, Johnson reports that the oxytocin, vasopressin, and opioid systems of mice raised in these ways are all malformed, potentially explaining the observed behaviors for the first time. How well mice bond may sound like a niche concern, but if we are doing something similar to our own offspring, people would likely be much more concerned.

“Babies exposed to antibiotics in the first year of life have been shown to have an increased risk of depression and behavioral difficulties in childhood,” Johnson told IFLScience. “We don't know if that is the antibiotics or the infection [the antibiotics were given for], but antifungals don't seem to have the same effect.”

Johnson isn't jumping to extrapolate to humans, noting she gave her mice large doses of broad-spectrum antibiotics, very different from what “a child would get for an ear infection.” Johnson's mice were also kept on the dose for 5 weeks, a significant part of a rodent's lifespan. Nevertheless, the link between gut bacteria and the brain has turned up some surprising results in the last decade, including Johnson's own work showing certain gut bacteria can affect mood and personality.

How might bacteria in the intestines affect brain development? Johnson told IFLScience the vagus nerve, which connects the gut to the brain, has been the subject of research and is considered a key player, although it is not always involved, while scientists also suspect an immune response.

“We did find an immune marker was depleted in certain brain regions [of the mice given antibiotics],” Johnson told IFLScience. Short-chain fatty acids produced by healthy gut bacteria can pass the blood-brain barrier, and a third theory proposes they are the link.

The situation is further complicated by Johnson's observation that, while the same parts of the brain were perturbed in germ-free mice and those given antibiotics, the changes were in opposite directions.

Johnson is interested in seeing what effect feeding mice probiotics or short-chain fatty acids might have. Since she previously demonstrated that people with more friends have higher pain tolerance, Johnson is particularly intrigued by the interaction she found between the microbiome and the opioid system essential for pain relief.

“We depend on antibiotics,” Johnson stressed to IFLScience. Any damage they might inflict is minor compared to their revolutionary role in slashing infant mortality. However, concerns about their effects could be another in the long list of reasons to crack down on antibiotic overuse, such as prescriptions for viral conditions against which they are useless.

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