Preterm and low birth weight babies are routinely given antibiotics to prevent, not just treat, infections, which they have a high risk of developing. Now, researchers from the University of Melbourne have published a study “Neonatal antibiotics have long term sex-dependent effects on the enteric nervous system” in The Journal of Physiology that has found that early life exposure to antibiotics in neonatal mice has long-lasting effects on their microbiota, enteric nervous system, and gut function. This could mean that babies given antibiotics may grow up to experience gastrointestinal issues.

This discovery by a team in the department of anatomy and physiology at the University reportedly is the first to show that antibiotics given to neonatal mice has these long-lasting effects which result in disturbed gastrointestinal function, including the speed of motility through the gut and diarrhea-like symptoms in adulthood.

“Infants and young children receive the highest exposures to antibiotics globally. Although there is building evidence that early life exposure to antibiotics increases susceptibility to various diseases including gut disorders later in life, the lasting impact of early life antibiotics on the physiology of the gut and its enteric nervous system (ENS) remains unclear,” write the investigators.

“We treated neonatal mice with the antibiotic vancomycin during their first 10 postnatal days, then examined potential lasting effects of the antibiotic treatment on their colons during young adulthood (6 weeks old). We found that neonatal vancomycin treatment disrupted the gut functions of young adult female and male mice differently. Antibiotic-exposed females had significantly longer whole gut transit while antibiotic-treated males had significantly lower fecal weights compared to controls. Both male and female antibiotic-treated mice had greater percentages of fecal water content.

Treatment had sexually dimorphic impact

“Neonatal vancomycin treatment also had sexually dimorphic impacts on the neurochemistry and Ca2+ activity of young adult myenteric and submucosal neurons. Myenteric neurons of male mice were more disrupted than those of females, while opposing changes in submucosal neurons were seen in each sex. Neonatal vancomycin also induced sustained changes in colonic microbiota and lasting depletion of mucosal serotonin (5-HT) levels. Antibiotic impacts on microbiota and mucosal 5-HT were not sex-dependent, but we propose that the responses of the host to these changes are sex-specific.

“This first demonstration of long-term impacts of neonatal antibiotics on the ENS, gut microbiota and mucosal 5-HT has important implications for gut function and other physiological systems of the host.”

The research team gave mice an oral dose of vancomycin every day for the first ten days of their lives. They were then reared normally until they were young adults, and their gut tissue was looked at to measure its structure, function, microbiota, and nervous system. The investigators found that changes were also dependent on the sex of the mice.

The females had long whole gut transit and the males had lower fecal weight than the control group. Both males and females had greater fecal water content, which is a diarrhea-like symptom.

Mice have many similarities to humans, but they are born with more immature guts than humans and have accelerated growth due to their shorter life spans. Their gut microbiota and nervous systems are less complex than humans, so the findings cannot yet be directly associated to human children and infants.

The researchers will be doing further studies on the mechanisms of antibiotics on the gut and the causes of the sex specific actions, and if early life antibiotic use has effects on metabolism and brain function.

“We are excited about the findings of our study which show that antibiotics given after birth could have prolonged effects on the enteric nervous system,” said Jaime Foong, PhD, lead physiologist. “This provides further evidence of the importance of microbiota on gut health and could introduce new targets to advance antibiotic treatment to very young children.”

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