The recent report of the synthesis of glycoproteins by the abundant intestinal symbionts Bacteroides showed that these organisms use a novel bacterial enzyme to decorate their surfaces with a sugar residue derived from their environment. As a first step in understanding the importance of these glycoproteins to the bacteria and to the bacterial-host symbiosis, we identified and characterized the abundant glycoproteins of Bacteroides distasonis (proposed reclassification as Parabacteroides distasonis) [Sakamoto M, Benno Y (2006) Int J Syst Evol Microbiol 56:1599-1605]. Using lectin-affinity purification followed by tandem mass spectrometry, we identified a family of at least nine glycoproteins, similar only to the S-layer glycoproteins of Tannerella forsythia. Analysis of one of these purified glycoproteins demonstrated that the glycan is primarily a polymer of xylose, a monosaccharide rarely found in bacterial glycans. Even more unexpected was the finding that seven of nine of the glycoprotein promoters undergo DNA inversion, a process that we show is active in their endogenous human environment. Using cross-species functional assays, we show that a single serine family site-specific recombinase globally mediates the inversions of these glycoprotein promoters. This regulatory mechanism is similar to that of the Bacteroides fragilis capsular polysaccharides and establishes DNA inversion as a general and ancient means of regulation of glycan-containing surface molecules of these important human intestinal symbionts.