Bile acid dysmetabolism in Bangladeshi infants is associated with poor linear growth, enteric inflammation, and small intestine bacterial overgrowth

Introduction: Environmental enteric dysfunction (EED) is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis. This study investigates 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 = .003) and sulfated primary bile acids (12.98% vs. <0.001%, p = .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 [B] = -0.01, p = 0.01) and height-for-age z scores (B; = -0.01, p = 0.03). Conjugated secondary bile acids were inversely associated with small intestine bacterial overgrowth (B; = -1096.68, p = 0.05). Fecal myeloperoxidase was associated with sulfated secondary bile acids (B; = -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). Discussion: 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.