Antibiotics given in infancy can disrupt development of the microbiome, resulting in increased levels of aggression later in life (Aug 2024, humanized mice) A gut reaction? The role of the microbiome in aggression Antibiotics

[Michael Harrop]

• https://www.israel21c.org/mice-given-antibiotics-as-babies-become-more-aggressive/
• https://www.sciencedirect.com/science/article/pii/S0889159124005336

Highlights​

• This is the first study to examine how the microbiome interacts with aggression through urine profiling. This analysis was particularly nuanced because not only did we compare basal urine metabolomes in response to microbiota manipulation (four unique study groups, above), but we also capture real-time metabolic responses to aggressive interactions by comparing samples taken before and after behavioral assays.
• Here, we expanded the study of brain function in the aggression-microbiota interplay, quantifying serotonin, serotonin turnover and tryptophan levels using HPLC as well as identifying key gene expression patterns using transcriptomics in five different regions of the brain. We examined gene expression related to serotonin and other neurotransmitter receptors in multiple brain regions, identifying the septum as an important brain region for regulation of aggression. Gene set enrichment analysis was also used to highlight other, less studied pathways (Rho GTPase and Reelin) associated with aggressive behavior in the context of the gut-brain-microbiome axis.
• The data generated in this study is rich (untargeted metabolomics of urine and transcriptomics of five brain regions), spanning four microbiota manipulation states, and will be publicly available, further extending the potential application of our research.
• We include a study of humanized mice using unique fecal samples of 1-month-old infants, collected nearly a month after early-life ABX administration. In previous work (Uzan-Yulzari et al. 2021, Nat Comm), we have demonstrated that ABX in this critical period of life can have lasting effects of childhood growth. Here, we extend these findings using samples from the same cohort. Using fecal samples collected weeks after ABX administration also reduces the direct chemical effects of ABX on the host, highlighting the causative role of the dysbiotic host microbiome and associated metabolome in driving aggressive behavior. We demonstrate that infant microbiota, perturbed within the first 48 h of life, has a lasting signature through 1 month of age that, when transplanted into GF mice, results in increased aggression (3–5 weeks after transplant) when compared to effects of stools of infants not exposed to any early-life antibiotics. The findings are revolutionary as they show how ABX-altered microbiota during a critical development window can lead to persisting behavioral deficits.

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Abstract​

Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. Here, we compared behavior profiles of control, germ-free (GF), and antibiotic-treated mice, as well as re-colonized GF mice to understand the impact of the gut microbiome on aggression using the resident-intruder paradigm.

Our findings revealed a link between gut microbiome depletion and higher aggression, accompanied by notable changes in urine metabolite profiles and brain gene expression.

This study extends beyond classical murine models to humanized mice to reveal the clinical relevance of early-life antibiotic use on aggression. Fecal microbiome transplant from infants exposed to antibiotics in early life (and sampled one month later) into mice led to increased aggression compared to mice receiving transplants from unexposed infants.

This study sheds light on the role of the gut microbiome in modulating aggression and highlights its potential avenues of action, offering insights for development of therapeutic strategies for aggression-related disorders.

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I've had quite a bit of experience with highly aggressive people who seem to have taken lots of antibiotics.