BACKGROUND Environmental enteric dysfunction(EED)is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis.Bile acids serve to facilitate lipid digestion and absorptio...BACKGROUND Environmental enteric dysfunction(EED)is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis.Bile acids serve to facilitate lipid digestion and absorption,regulate metabolic pathways associated with childhood growth and inflammation,and may be affected by EED.AIM To investigate bile acid metabolism in Bangladeshi children with EED and its association with growth impairment.METHODS We conducted a cross-sectional study of 100 Bangladeshi infants(aged 6-9 months)and quantified serum and fecal bile acids using LC-MS/MS.We compared profiles to a control group of 6 American children(6-12 months)and 80 older Bangladeshi children(aged 2 years).RESULTS Bangladeshi infants had higher levels of plasma unconjugated primary(65.23%vs 44.25%,P=0.003)and sulfated primary bile acids(12.98%vs<0.001%,P=0.01),with lower primary conjugated bile acids(0.69%vs 2.74%,P≤0.001)compared to American children.Stool unconjugated primary bile acids were inversely associated with weight-for-age[regression coefficient(β)=-0.01,P=0.01]and height-for-age Z scores(β=-0.01,P=0.03).Conjugated secondary bile acids were inversely associated with small intestine bacterial overgrowth(β=-1096.68,P=0.05).Fecal myeloperoxidase was associated with sulfated secondary bile acids(β=-0.40,P=0.04).Compared to 2-year-old children,the Bangladeshi infant’s serum had higher levels of unconjugated primary bile acids(65.23%vs 9.20%,P≤0.001)and lower levels of primary conjugated bile acids(0.69%vs 80.38%,P≤0.001).CONCLUSION Our data suggests an age-dependent defect in conjugation of primary bile acids in Bangladeshi children with compensatory hydrophilic shunting.Additionally,bile acid profiles are associated with intestinal overgrowth.展开更多
基金Supported by Children’s Hospital Foundation at VCU,No.1K23HD097282(to Donowitz JR)National Institutes of Health,No.5R01AI043596(to Donowitz JR)+6 种基金Bill and Melinda Gates Foundation,No.OPP1017093VA Merit Award,No.1I01BX005730VA ShEEP Grants,No.1 IS1 BX004777-01National Institutes of Health Grant,No.2R56DK115377-05A1PIDS Summer Research Scholars AwardVCU SOM Dean’s Summer Research Fellowshipand Research Career Scientist Award from the Department of Veterans Affairs,No.IK6BX004477.
文摘BACKGROUND Environmental enteric dysfunction(EED)is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis.Bile acids serve to facilitate lipid digestion and absorption,regulate metabolic pathways associated with childhood growth and inflammation,and may be affected by EED.AIM To investigate bile acid metabolism in Bangladeshi children with EED and its association with growth impairment.METHODS We conducted a cross-sectional study of 100 Bangladeshi infants(aged 6-9 months)and quantified serum and fecal bile acids using LC-MS/MS.We compared profiles to a control group of 6 American children(6-12 months)and 80 older Bangladeshi children(aged 2 years).RESULTS Bangladeshi infants had higher levels of plasma unconjugated primary(65.23%vs 44.25%,P=0.003)and sulfated primary bile acids(12.98%vs<0.001%,P=0.01),with lower primary conjugated bile acids(0.69%vs 2.74%,P≤0.001)compared to American children.Stool unconjugated primary bile acids were inversely associated with weight-for-age[regression coefficient(β)=-0.01,P=0.01]and height-for-age Z scores(β=-0.01,P=0.03).Conjugated secondary bile acids were inversely associated with small intestine bacterial overgrowth(β=-1096.68,P=0.05).Fecal myeloperoxidase was associated with sulfated secondary bile acids(β=-0.40,P=0.04).Compared to 2-year-old children,the Bangladeshi infant’s serum had higher levels of unconjugated primary bile acids(65.23%vs 9.20%,P≤0.001)and lower levels of primary conjugated bile acids(0.69%vs 80.38%,P≤0.001).CONCLUSION Our data suggests an age-dependent defect in conjugation of primary bile acids in Bangladeshi children with compensatory hydrophilic shunting.Additionally,bile acid profiles are associated with intestinal overgrowth.
