Host–microbe interactions shaping the gastrointestinal environment

• The microbiota is an interdependent network of microbes influencing pathogen invasion.
• Diet, mucus, and microbiota-derived metabolites regulate commensal colonization.
• The microbiota maintains a reciprocal relationship with IgA and AMPs during homeostasis.

Tremendous advances have been made in mapping the complexity of the human gut microbiota in both health and disease states. These analyses have revealed that, rather than a constellation of individual species, a healthy microbiota comprises an interdependent network of microbes. The microbial and host interactions that shape both this network and the gastrointestinal environment are areas of intense investigation. Here we review emerging concepts of how microbial metabolic processes control commensal composition, invading pathogens, immune activation, and intestinal barrier function. We posit that all of these factors are critical for the maintenance of homeostasis and avoidance of overt inflammatory disease. A greater understanding of the underlying mechanisms will shed light on the pathogenesis of many diseases and guide new therapeutic interventions.