Significance Mucus with its major constituent, the gel-forming mucins, is important for protecting the host epithelium from bacteria. Under normal conditions, these mucin networks are constantly released into the small intestinal lumen. This release required a proteolytic cleavage in the mucin by the metalloprotease meprin β and was absent in germ-free animals but induced by bacteria. The small intestinal mucus in cystic fibrosis is also attached, not due to lack of enzyme, but rather that the mucin is not properly unfolded in the absence of a functional cystic fibrosis transmembrane conductance regulator channel and sufficient bicarbonate levels. Mucus can thus appear both attached and released as part of a system controlling bacterial removal. This new concept may lead to new ways for the treatment and therapy of cystic fibrosis.