DP, Gewirtz AT. Detectable serum flagellin and lipopolysaccharide and upregulated anti-flagellin and lipopolysaccharide immunoglobulins in human short bowel syndrome. Am J Physiol Regul Integr Comp Physiol 294: R402-R410, 2008. First published November 14, 2007 doi:10.1152/ajpregu.00650.2007.-Gut barrier dysfunction may occur in short bowel syndrome (SBS). We hypothesized that systemic exposure to flagellin and lipopolysaccharide (LPS) in SBS might regulate specific immune responses. We analyzed serial serum samples obtained from parenteral nutrition (PN)-dependent patients with SBS versus non-SBS control serum. Serum from 23 adult SBS patients was obtained at baseline and 4, 8, 12, 16, 20, and 24 wk in a trial of modified diet with or without growth hormone. Control serum was obtained from 48 healthy adults and 37 adults requiring PN during critical illness. Serum flagellin was detected by an ELISA recognizing an array of gram-negative flagellins, and LPS was detected by limulus assay. Serum flagellin-and LPS-specific immunoglobulin levels (IgM, IgA, and IgG) were determined by ELISA. Serum flagellin and LPS were undetectable in control subjects. In contrast, serum flagellin, LPS, or both were detected in 14 SBS patients (61%) during one or more time points [flagellin alone, 5/23 (22%); LPS alone, 6/23 (26%); or flagellin ϩ LPS, 3/23 (13%)]. Flagellin-specific serum IgM, IgA, and IgG levels were markedly increased in SBS patients compared with both control populations and remained elevated during the 6-mo study period. LPS-specific IgA was significantly higher in SBS patients compared with healthy controls; LPS-specific IgM, IgA, and IgG levels each decreased over time in association with PN weaning. We conclude that adults with PN-dependent SBS are systemically exposed to flagellin and LPS, presumably from the gut lumen. This likely regulates innate and adaptive immune responses to these specific bacterial products. parenteral nutrition; intestinal barrier function SHORT BOWEL SYNDROME (SBS) occurs after massive small bowel resection and is an important clinical entity, with significant morbidity and mortality (13,36). SBS is characterized by chronic diarrhea and malabsorption, dehydration and malnutrition, and, in patients requiring parenteral nutrition (PN), frequent infections (13,36). Unfortunately, SBS and PN administration are each associated with infection by enteric gramnegative bacteria, suggesting that failure of the gut barrier occurs (2,4,5,18,20,22,24,25,33,34).