Microbial modulation of innate defense: goblet cells and the intestinal mucus layer

The gastrointestinal epithelium is covered by a protective mucus gel compos ed predominantly of mucin glycoproteins that are synthesized and secreted b y goblet cells. Changes in goblet cell functions and in the chemical compos ition of intestinal mucus are detected in response to a broad range of lumi nal insults, including alterations of the normal microbiota. However, the r egulatory networks that mediate goblet cell responses to intestinal insults are poorly defined. The present review summarizes the results of developme ntal, gnotobiotic, and in vitro studies that showed alterations in mucin ge ne expression, mucus composition, or mucus secretion in response to intesti nal microbes or host-derived inflammatory mediators. The dynamic nature of the mucus layer is shown. Available data indicate that intestinal microbes may affect goblet cell dynamics and the mucus layer directly via the local release of bioactive factors or indirectly via activation of host immune ce lls. A precise definition of the regulatory networks that interface with go blet cells may have broad biomedical applications because mucus alterations appear to characterize most diseases of mucosal tissues.