2021- Effects of early-life penicillin exposure on the gut microbiome and frontal cortex and amygdala gene expression

Journal: iScience, July 2021, Full Article Here

Who are the authors?

Angelina Volkova, Kelly Ruggles, Anjelique Schulfer, Zhan Gao, Stephen D. Ginsberg, and Martin J. Blaser

Are there A.K.A.s to be aware of?

Penicillin– other names: Amoxil, Bactocil, Bicillin L-A, Cloxapen, Crysticillin, Dynapen, Geocillin (for the sake of brevity, not all names are included here -do your research!)

Microbiome – microorganisms that live in your intestines and are very important for your health

Amygdala – a brain center for emotion-information processing

Prefrontal Cortex – the front part of your brain; it deals with decision making, planning, short term memory, and other functions of day to day life

Gene expression – you’re born with genes that express themselves in certain ways right? Brown eyes, black hair, your susceptibility to cancer, depression, or other illnesses…; well, what they study here is how penicillin affects the gene expression of a child’s microbiome, amygdala, and prefrontal cortex when a mother uses penicillin during pregnancy.

Why was this study/article written?

To study environmental factors in early childhood development that may possibly contribute to the rise in incidences of childhood neurodevelopmental disorders. The use of antibiotics is considered a new environmental factor that did not exist before 1945. The importance of the human microbiome and how it can be affected by environmental factors is also discussed due to the microbiomes role in health, as well as the gut-brain connection that is supported through research.

What is the article about?

To examine the effect of penicillin (a widely used antibiotic) on the gene expression of a child’s amygdala, prefrontal cortex (a part of the brain), and the microbiome when a mother uses penicillin during pregnancy.

What does previous research say about gut-brain axis?

Previous research has suggested that modulating the gut-brain axis, especially early in development, may alter the risk of developing neuropsychiatric and/or neurodegenerative disorders in adulthood. It has also been suggested that early-life antibiotic exposure may be associated with neurodevelopmental disorders, but the literature is conflicting. Additionally, there is evidence that changes in specific microbial taxa may be directly associated and/or mechanistic drivers of a mosaic CNS including select gene expression and/or key developmental pathways.

What hypotheses were tested?

1. Antibiotic exposure may have potentially deleterious organizational effect by perturbing the developing microbiome in early life and subsequently altering signaling within the developing brain.

2. Selective gut microbiome changes in specific taxa linked to brain level gene expression differences can be identified during the early postnatal period within mouse brain regions relevant to dysfunction observed in human neurodevelopmental disorders.

What was found; what were the correlations or causal links found?

The present study found that there were a large number of significantly differentially expressed genes in both the frontal cortex and amygdala of mice exposed in their early life to low-dose penicillin (LDP). There were also significant changes in gene expression in both the frontal cortex and amygdala in mice exposed to LDP. Additionally, there were significant differences in a-diversity and b-diversity between the experimental groups, as well as significant differences in relative abundance when comparing the gene tertiles with relative abundance of each taxon identified by the MaAsLin2 analysis.

Analysis of gene expression in the frontal cortex and amygdala revealed hundreds of differentially expressed genes in both comparisons between the control group and the antibiotic-exposed (STAT and STAT-Birth) groups. Further experiments are needed to validate these findings and to test for causal inferences. The study also linked changes in specific microbial taxa to differences in CNS gene expression, with potential implications for neurodevelopmental disorders.

What are the limitations of the study?

The limitations of this study include not being able to assess whether the changes were due to LDP exposure directly or were due to the effects on the intestinal microbiota, not being able to randomize the pups within a litter, and studying the pups at only a single time point (PND10).

Additionally, the low doses used in this study suggest that the effects observed in CNS expression could also be due to the penicillin effects on the mother herself, with secondary effects on the development of the pups.

What do the authors suggest people do with the information?

Future studies should examine the durability of the findings, the effects of the penicillin on the mother, the effects of randomizing the pups within a litter, and the causal inferences between early-life antibiotic exposure and neurodevelopmental disorders such as ASD and ADHD. Additionally, further experiments should be conducted to validate the findings and to assess the extent of expression level changes within brain regions vulnerable to perinatal insults.

Also, they should examine the effects of early-life antibiotic perturbation of the intestinal microbiome in the context of CNS development, with extensive assessment of the microbiome, expression profiling of key brain circuits, and physiological and/or behavioral readouts to allow testing for causal inferences. Additionally, further experiments should be conducted to validate these findings and to determine the durability of the findings, as well as to assess the direct effects of antibiotics on the brain or their effects via their actions on the human microbiome.  ,

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