A gut reaction? The role of the microbiome in aggression.

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.

The effect of testosterone on the gut microbiome in mice.

The role of hormones in gut-brain crosstalk is largely elusive, but recent research supports specific changes in hormone levels correlated with the gut microbiota. An interesting but unstudied area in microbial endocrinology is the interplay between the microbiota and sex hormones. The aim of this study is to investigate the effect of testosterone and sex on the mouse gut microbiome. We use in vitro experiments to test direct effects of testosterone on bacteria in fecal samples collected from male and female mice pre- and post-puberty. Sex-specific microbial and metabolic differences surrounding puberty are also examined in vivo. We then explore effects of testosterone supplementation in vivo, characterizing microbiota and metabolomes of male and female mice. We detect sex-specific differences in microbiota and associated metabolites of mice post-puberty, but in vitro experiments reveal that testosterone only affects microbiota of fecal samples collected before puberty. Testosterone supplementation in vivo affects gut microbiota and metabolomes in both male and female mice. Taking our results from in vitro and in vivo experiments, we conclude that the shift in the microbiome after puberty is at least partially caused by the higher levels of sex hormones, mainly testosterone, in the host.

Microbiome signature of posttraumatic stress disorder and resilience in youth.

OBJECTIVE: Identifying biomarkers that can distinguish trauma-exposed youth at risk for developing posttraumatic pathology from resilient individuals is essential for targeted interventions. As trauma can alter the microbiome with lasting effects on the host, our longitudinal, multimeasure, cross-species study aimed to identify the microbial signature of posttraumatic stress disorder (PTSD). METHOD: We followed children exposed to war-related trauma and matched controls from early childhood (Mage = 2.76 years, N = 232) to adolescence (Mage = 16.13 years, N = 84), repeatedly assessing posttraumatic symptomatology and maternal caregiving. In late adolescence, we collected fecal samples from mothers and youth and assessed microbiome composition, diversity, and mother-child microbial synchrony. We then transplanted adolescents' fecal samples into germ-free mice to determine if behavioral changes are observed. RESULTS: Youth with PTSD exhibited a distinct gut microbiome profile and lower diversity compared to resilient individuals, and microbiome diversity mediated the continuity of posttraumatic symptomatology throughout development. Low microbiome diversity correlated with more posttraumatic symptoms in early childhood, more emotional and behavioral problems in adolescence, and poor maternal caregiving. Youth with PTSD demonstrated less mother-child microbial synchrony, suggesting that low microbial concordance between mother and child may indicate susceptibility to posttraumatic illness. Germ-free mice transplanted with microbiomes from individuals with PTSD displayed increased anxious behavior. CONCLUSIONS: Our findings provide evidence that the trauma-associated microbiome profile is at least partially responsible for the anxiety component of the PTSD phenotype and highlight microbial underpinnings of resilience. Further, our results suggest that the microbiome may serve as additional biological memory of early life stress and underscore the potential for microbiome-related diagnosis and treatment following trauma. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Children with idiopathic short stature have significantly different gut microbiota than their normal height siblings: a case-control study.

Objectives: To investigate the role of gut microbiota (GM) in pathogenesis of idiopathic short stature (ISS) by comparing GM of ISS children to their normal-height siblings. Methods: This case-control study, conducted at the Schneider Children's Medical Center's Institute for Endocrinology and Diabetes between 4/2018-11/2020, involved 30 pairs of healthy pre-pubertal siblings aged 3-10 years, each comprising one sibling with ISS and one with normal height. Outcome measures from fecal analysis of both siblings included GM composition analyzed by 16S rRNA sequencing, fecal metabolomics, and monitoring the growth of germ-free (GF) mice after fecal transplantation. Results: Fecal analysis of ISS children identified higher predicted levels of genes encoding enzymes for pyrimidine, purine, flavin, coenzyme B, and thiamine biosynthesis, lower levels of several amino acids, and a significantly higher prevalence of the phylum Euryarchaeota compared to their normal-height siblings (p<0.001). ISS children with higher levels of Methanobrevibacter, the dominant species in the archaeal gut community, were significantly shorter in stature than those with lower levels (p=0.022). Mice receiving fecal transplants from ISS children did not experience stunted growth, probably due to the eradication of Methanobrevibacter caused by exposure to oxygen during fecal collection. Discussion: Our findings suggest that different characteristics in the GM may explain variations in linear growth. The varying levels of Methanobrevibacter demonstrated within the ISS group reflect the multifactorial nature of ISS and the potential ability of the GM to partially explain growth variations. The targeting of specific microbiota could provide personalized therapies to improve growth in children with ISS.