Early exposure to penicillins could alter human brain development in areas responsible for cognitive and emotional functions.
When one of the founding fathers of our Western medicine, Hippocrates, postulated some 2,500 years ago that all diseases begin in the gut, he was on to something. In recent years, insights into the role of the gut microbiome in the immune and neuroendocrine systems have renewed our understanding of many diseases, from cancer to MS. In a recent post, we had described possible pathways to the brain through which an abnormal gut microbiome may be involved in the development of neurological and even neurodegenerative disorders.
A group of scientists from Rutgers University, New Jersey, have now gone a step further and in a recently published paper show how these effects can also span large periods of time. They studied the effects of antibiotics on gut flora and gene expression in the brain during the fetal period and early childhood.1,2
The maturation of the central nervous system is a vulnerable process.
A specially established experimental system now revealed links between specific gut microbiome populations and the early expression of certain affected genes.
The researchers exposed mice to low doses of penicillin before and after birth, which led to significant changes in the structure and composition of the gut flora. Not surprising as far as that goes. The exciting thing is that this changed the set of active or expressed genes in several signalling pathways involved in neuropsychiatric and neurodevelopmental disorders. Gene expression between treated and non-treated animals differed particularly in the frontal cortex and amygdala, two key areas involved in memory development and anxiety and stress responses. The researchers hope to further develop their model and show more precisely which molecules and genes are centrally involved.
These observations could become highly relevant practically because penicillins (such as ampicillin and amoxicillin) are the most commonly used antibiotics in children worldwide. In the United States, children receive an average of nearly three treatments of antibiotics in the first two years of life. In many other countries, exposure rates are similar or higher. In Germany, children also receive more antibiotics than adults in subsequent years: Nationwide, every second child between the ages of three and six is prescribed an antibiotic at least once a year. The most common causes: acute otitis media, feverish colds and flu. Since these are mostly viral infections, antibiotics are often ineffective and, according to the guidelines, are only indicated in exceptional cases. Nevertheless, for example, 9% of ENT physicians, 17% of paediatricians and as many as 33% of GPs prescribe antibiotics for non-purulent middle ear infections.3
In a preliminary paper, the team had already documented the effects of antibiotic administration in critical developmental phases on immune function and metabolism. The third important development in this early stage of life concerns the brain. In recent decades, the frequency of neurodevelopmental disorders in children has increased, the authors point out.
"Environmental exposures at an early stage of development are thought to be crucial in triggering such pathologies. The rapid increase in the number of cases is consistent with changes in external factors, but few influences are global or of sufficient magnitude to explain trends in these disorders in several countries around the world. The challenge is to identify the impairments from the environment, understand the neurobiological targets and identify interventions to improve public health."
References:
1. Volkova, A. et al. Effects of early-life penicillin exposure on the gut microbiome and frontal cortex and amygdala gene expression. iScience 24, (2021).
2. Antibiotics in Early Life Could Affect Brain Development. https://www.rutgers.edu/news/antibiotics-early-life-could-affect-brain-development.
3. Faktencheck Antibiotika. https://faktencheck-gesundheit.de/de/faktenchecks/antibiotika/ergebnis-ueberblick/.