Abstract
RATIONALE: Researchers in psychiatry and neuroscience are increasingly recognizing the importance of gut-brain communication in mental health. Both genetics and environmental factors influence gut microbiota composition and function. This study examines host-microbe signaling at the gastrointestinal barrier to identify bottom-up mechanisms of microbiota-brain communication. OBJECTIVES: We examined differences in gut microbiota composition and fecal miRNA profiles in BALB/c and C57BL/6 mice, in relation to gastrointestinal homeostasis and evaluated the response to perturbation of the gut microbiota by broad-spectrum antibiotic treatment. METHODS AND RESULTS: Differences in the gut microbiota composition between BALB/c and C57BL/6 mice, evaluated by fecal 16S rRNA gene sequencing, included significant differences in genera Prevotella, Alistipes, Akkermansia, and Ruminococcus. Significant differences in fecal miRNA profiles were determined using the nCounter NanoString platform. A BLASTn analysis identified conserved fecal miRNA target regions in bacterial metagenomes with 14 significant correlations found between fecal miRNA and predicted taxa relative abundance in our dataset. Treatment with broad-spectrum antibiotics for 2 weeks resulted in a host-specific physiological response at the gastrointestinal barrier including a decrease in barrier permeability in BALB/c mice and alterations in the expression of barrier regulating genes in both strains. Genera Parabacteroides and Bacteroides were associated with changes in barrier function. CONCLUSIONS: The results of this study provide insight into how specific taxa influence gut barrier integrity and function. More generally, these data in the context of recent published studies makes a significant contribution to our understanding of host-microbe interactions providing new knowledge that can be harnessed by us and others in future mechanistic studies.