Periodic Reporting for period 2 - BEHAVIOME (Aggression and the Gut Microbiome)
Reporting period: 2022-09-01 to 2024-02-29
Aggressive behavior is common throughout the animal kingdom and also affects large swaths of the global human population. Recent research has shown that the gut microbiota, the collection of microorganisms in our guts (bacteria, fungi, viruses, and others) can affect a range of host functions (e.g. digestion, health status) and even behaviors. In our BEHAVIOME research, we are aiming to identify the connection between these microorganisms and aggressive behavior using fruit flies and mice as our model organisms. We are particularly interested in how antibiotic depletion of some or all of the microbiota affects this behavior in adults and also in very early life: in utero, during labor, and in the first days of life. Understanding how microbiota perturbation affects aggression will allow for research into treatments - for example, a mix of bacterial by-products, termed “post-biotics” could be prescribed together with antibiotics to reduce any unintended side-effects of this important treatment.
We have recently shown that microbiota depletion, both with antibiotics and when animals are raised in sterile, germ-free environments, increases aggressive behavior in both mice and fruit flies. Interestingly, not all antibiotics lead to this finding suggesting that some microbes are more important than others in regulating this behavior. In addition to direct manipulation of the microbiota, we also administered antibiotics to pregnant mouse dams but stopped the treatment when pups were born and discovered that even this indirect exposure to antibiotics caused pups to be more aggressive when they reached maturity. Lastly, we aimed to bring our research closer to the clinic. We collected fecal samples of one-month-old (human) babies who had and had not been exposed to antibiotics in the first days of life and transferred these feces to mice that were sterile (i.e. did not have their own microbiome). This resulted in colonization of the mice by the babies’ microbiota. Following this colonization, we found that mice that received the microbiota of antibiotic-exposed babies were more aggressive than those that received feces from the un-exposed babies.
This is one of the first studies of the interaction between the gut microbiota and aggression and the first evidence that early life antibiotic treatment can lead to aggression later in life, as demonstrated through humanizing mice with babies’ microbiota. We anticipate uncovering specific mechanisms underlying these interactions by examining gene expression in brains of mice and flies and also diving deeper into the metabolic profiles of both species at various body sites. This will allow us to identify microbial and metabolite targets to reduce aggression in cases where the microbiota is perturbed.