Aggression: A gut reaction? The effects of the gut microbiome on aggression

Abstract

Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. In our investigation, we meticulously examined the behavioral patterns of four groups of mice – wild-type, germ-free (GF), mice treated with antibiotics, and recolonized GF mice – to gain mechanistic insights into the impact of the gut microbiome on aggression. We discovered a significant correlation between diminished microbiome and increased aggression. Importantly, this behavioral shift could be restored when a WT microbiota was reinstated. Microbiota manipulation also significantly altered brain function, particularly in aggression-associated genes, and urine metabolite profiles. Notably, our study extends beyond the murine model, shedding light on clinical implications of early-life antibiotic exposure. We found that fecal microbiome transplants from 1mo old infants prescribed antibiotics during their first days of life led to a marked increase in aggression in recipient mice. This research demonstrates that the microbiota modulates aggression and underscores its importance in the realm of behavioral science.One-Sentence SummaryThe antibiotic-altered gut microbiome is implicated in increased aggression. It also leads to altered brain function, particularly in genes linked to aggression, and urine metabolite profiles showing a multi-system response to microbiota disruption.

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“…In animal models, when the fecal microbes from animals reared on Westernized dietary patterns are transferred to otherwise healthy animals consuming normal lab chow, the recipient animals show cognitive deficits and behavioral changes [227][228][229]. Remarkably, a new study currently in preprint shows that fecal microbiome transplants from one-month-old human infants prescribed antibiotics during their first days of life (i.e., in a state of dysbiosis) lead to significant increases in aggression in recipient mice [230]. Chronic unpredictable stress also disturbs the gut microbiome, and the transfer of fecal microbes from animals that experienced chronic unpredictable stress to healthy animals leads to anxiety and depressivelike symptoms among otherwise normal recipient animals [231].…”

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“…Strong support for a microbiome-behavior link can be found in fecal transplant studies; that is, when fecal material from animals with nutrient-related or stress-induced dysbiosis (or from human donors with mental disorders) is transplanted into otherwise healthy animals, the recipients have observable neuropsychiatric disturbances, as found in the dysbiotic donors [80][81][82][83]. For example, the transfer of fecal material from human infants with dysbiosis (vs. the transfer of microbiota from healthy animals) to recipient lab animals leads to aggressive-like behavior in recipients lab animals [84]. Mechanistic pathways have been illuminated-recipients of dysbiotic microbiota are noted to display alterations to metabolic pathways, disturbances of the intestinal barrier, changes in neurotransmitter levels (e.g., serotonin and gamma-aminobutyric acid), and micro-RNA alterations in the frontal cortex [85][86][87][88].…”