The effects of inflammation, infection and antibiotics on the microbiota-gut-brain axis.

ABSTRACT

Animal studies have demonstrated that the early phase of enteric infection is accompanied by anxiety-like behavior, which is mediated through vagal ascending pathways. Chronic infection alters gut function, including motility and visceral sensitivity, as well as feeding patterns, anxiety and depression-like behavior. These effects are likely immune-mediated, and involve changes in pro-inflammatory cytokines and altered metabolism of kynurenine/tryptophan pathways. Clinical studies have shown that chronic gastrointestinal infections lead to malnutrition and stunting, resulting in impaired cognitive function. Accumulating evidence suggests that in addition to pathogens, the commensal gastrointestinal microbiota also influences gut function and host's behavior. Both animal and clinical studies have demonstrated changes in behavior and brain chemistry after induction of intestinal dysbiosis by administration of antibiotics. This concept of microbiota-gut-brain interactions opens a new field of research aimed at developing microbial-directed therapies to treat a broad spectrum of human conditions, including chronic gastrointestinal and psychiatric disorders.