title: Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure.
abstract: Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r = -0.50, p < 0.05). In ileum, the inflammation grades were inversely associated with farnesoid X receptor (FXR) expression (r = -0.55, p < 0.05). In liver, the expression of induction of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients.
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute for Pediatric Research, Shanghai, China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Xiao
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Shanghai Institute for Pediatric Research, Shanghai, China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
authors.forename: Ke-Jun
authors.initials: KJ
authors.lastname: Zhou
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Lu
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute for Pediatric Research, Shanghai, China.|Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
mesh_terms: D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism*; D002675:Child, Preschool; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D007077:Ileal Diseases / Q000473:pathology; D007223:Infant; D015850:Interleukin-6; D007410:Intestinal Diseases / Q000150:complications / Q000473:pathology*; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D002790:Cholesterol 7-alpha-Hydroxylase; D005346:Fibroblast Growth Factors; D015850:Interleukin-6; D018160:Receptors, Cytoplasmic and Nuclear; D014409:Tumor Necrosis Factor-alpha; D000099150:Receptor, Farnesoid X-Activated; C117476:FGF19 protein, human; C553219:CYP7A1 protein, human