Sat. Feb 4th, 2023
Getting antibiotics as a baby can have lasting effects on the brain and behavior

Banishing bacteria from the body with antibiotics around birth may cause confused signals in the brain and lasting changes in behavior, a series of studies suggest.

In the latest study, which only involved mice, researchers found that low doses of penicillin given to pups before and after birth caused changes in their blood-brain barrier and brain chemistry. The mice became more aggressive and showed reduced social behavior, researchers reported Monday Nature communication.

That study supports previous work in mice, as well as humans, and shows that the microbes residing in our guts can indeed cause changes in our brains. In a small, remarkable 2014 study, researchers found that eating two servings of yogurt with bacteria per day for four weeks changed brain chemistry in a dozen healthy women. In January, New Zealand researchers published a study of 871 children who found a link between getting antibiotics in the first year of life and more behavioral problems and symptoms of depression when the children reached the ages of seven and eleven.

While evidence for the so-called “gut-brain axis” is mounting, it’s still unclear exactly how antibiotics and gut microbes interfere with our noggins. Antibiotics certainly do not directly cause these changes. And gut microbes don’t move on to better, smarter digs. Instead, researchers hypothesize that antibiotics and other disruptions in microbial power could alter the brain and our behavior via chemical signals that affect the immune system, metabolism and the brain itself. Gut microbes have been caught making most of the neurotransmitters our brains use to self-regulate, including GABA, serotonin, dopamine, and norepinephrine. Gut microbes also make short-chain fatty acids such as butyrate, propionate and acetate, which may be involved in energy balance and metabolism. And the gut inhabitants can influence cytokines, chemical signals used by the immune system.

As researchers work feverishly to figure out how these manipulative microbes could help cause or cure disease, the findings raise new concerns about altering microbial communities with unnecessary doses of antibiotics while the brain and body are still developing. As Ars previously reported, antibiotics given to human babies early in life can lead to obesity later in life. And previous research in mice has shown that high doses of antibiotics can cause long-lasting brain and metabolic changes in adult and adolescent mice.

The brain on antibiotics

In the new study, a group of researchers from McMaster University in Canada wanted to look at the more clinically relevant effect of low doses on babies. Mouse pups were exposed to low doses of penicillin before and after birth via blood and breast milk from their mothers. When they were six weeks old, researchers then subjected them to a series of behavioral tests and assessed their brain development.

Using a total of 72 mice, researchers found that mice exposed to penicillin were less social, slightly less anxious and more aggressive than mice that were not exposed. In an aggression test, 42 percent of exposed mice were rated spicy compared to just 9 percent in the unexposed control group. Using a separate group of mice, researchers found that simultaneous doses of the probiotic, Lactobacillus rhamnosus, could partially block the effects of the antibiotic.

When the researchers peeked into the mice’s brains, they found thinner blood-brain barriers in exposed mice, plus relatively high activity of a gene linked to aggressive behavior. They also found increased expression of cytokines in the brain.

“While all of these data obtained in rodents cannot be directly extrapolated to humans,” the authors write, “they add the need to carefully consider the potential negative long-term effects of AB in early life. [antibiotic] exposure.”

Besides the problem of extrapolating mouse data to human health, the study had some other limitations. As researchers begin to replicate and expand this line of research, it will be important to first disentangle the effects of antibiotic exposure and after the birth. It is possible that the antibiotics given to the mother mice have been disrupted their microbial communities, which they pass on to their pups. It will be important to disentangle maternal microbiome effects from postnatal antibiotic effects. Also, the period of exposure to antibiotics for the pups was quite long. Future studies should look at shorter, more common exposures.

Indeed, “these results warrant further investigation into the potential role of antibiotic use in the early years of life in the development of neuropsychiatric disorders, and its potential attenuation by beneficial bacteria,” the authors conclude.

Nature communication2017. DOI: 10.1038/ncomms15062 (About DOIs).

By akfire1

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