Alice Santos-Silva1,2, Dora Brites3, Ermelinda Santos Silva4,5,6,7, Susana Rocha1,2, Rita Candeias Ramos3, Helena Coutinho3, Cristina Catarino1,2, Fernanda Teixeira8, Graça Henriques8, Ana Isabel Lopes9,10. 1. UCIBIO - Applied Molecular Biosciences Unit, Biochemistry Laboratory, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. 2. Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. 3. Department of Pharmaceutical Sciences and Medicines, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal. 4. Gastroenterology Unit, Pediatrics Division, Child and Adolescent Department, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Porto, Portugal. ermelinda.dca@chporto.min-saude.pt. 5. Integrated Master in Medicine, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal. ermelinda.dca@chporto.min-saude.pt. 6. UCIBIO - Applied Molecular Biosciences Unit, Biochemistry Laboratory, Department of Biological Sciences, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. ermelinda.dca@chporto.min-saude.pt. 7. Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. ermelinda.dca@chporto.min-saude.pt. 8. CoreLab, Pathology Department, Hospital de Santo António, Centro Hospitalar Universitário do Porto, Porto, Portugal. 9. Clínica Universitária de Pediatria, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. 10. Pediatric Gastroenterology Unit, Pediatrics Department, Hospital Universitário de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal.
Abstract
BACKGROUND: At birth, human neonates are more likely to develop cholestasis and oxidative stress due to immaturity or other causes. We aimed to search for a potential association between bile acids profile, redox status, and type of diet in healthy infants. METHODS: A cross-sectional, exploratory study enrolled 2-month-old full-term infants (n = 32). We measured plasma bile acids (total and conjugated), and red blood cell (RBC) oxidative stress biomarkers. The type of diet (breastfeeding, mixed, formula) was used as an independent variable. RESULTS: Plasma total bile acids medium value was 14.80 µmol/L (IQR: 9.25-18.00). The plasma-conjugated chenodeoxycholic acid percentage (CDCA%) correlated significantly and negatively with RBCs membrane-bound hemoglobin percentage (MBH%) (r = -0.635, p < 0.01) and with RBC-oxidized glutathione (r = -0.403, p < 0.05) levels. RBC oxidative stress biomarkers (especially MBH%) were predictors of conjugated CDCA%, and this predictive ability was enhanced when adjusted for the type of diet (MBH, r = 0.452, p < 0.001). CONCLUSIONS: Our data suggest that the bile acid profile might play a role in the regulation of redox status (or vice versa) in early postnatal life. Eventually, the type of diet may have some impact on this process. IMPACT: The conjugated CDCA% in plasma is negatively correlated with biomarkers of RBC oxidative stress in healthy infants. Specific biomarkers of RBC oxidative stress (e.g. MBH, GSH, GSSG) may be promising predictors of conjugated CDCA% in plasma. The type of diet may influence the predictive ability of hit RBC oxidative stress biomarkers (e.g. MBH, GSH, GSSG). Our findings suggest a link between plasma bile acids profile and the RBC redox status in healthy infants, eventually modulated by the type of diet. The recognition of this link may contribute to the development of preventive and therapeutic strategies for neonatal cholestasis.
BACKGROUND: At birth, human neonates are more likely to develop cholestasis and oxidative stress due to immaturity or other causes. We aimed to search for a potential association between bile acids profile, redox status, and type of diet in healthy infants. METHODS: A cross-sectional, exploratory study enrolled 2-month-old full-term infants (n = 32). We measured plasma bile acids (total and conjugated), and red blood cell (RBC) oxidative stress biomarkers. The type of diet (breastfeeding, mixed, formula) was used as an independent variable. RESULTS: Plasma total bile acids medium value was 14.80 µmol/L (IQR: 9.25-18.00). The plasma-conjugated chenodeoxycholic acid percentage (CDCA%) correlated significantly and negatively with RBCs membrane-bound hemoglobin percentage (MBH%) (r = -0.635, p < 0.01) and with RBC-oxidized glutathione (r = -0.403, p < 0.05) levels. RBC oxidative stress biomarkers (especially MBH%) were predictors of conjugated CDCA%, and this predictive ability was enhanced when adjusted for the type of diet (MBH, r = 0.452, p < 0.001). CONCLUSIONS: Our data suggest that the bile acid profile might play a role in the regulation of redox status (or vice versa) in early postnatal life. Eventually, the type of diet may have some impact on this process. IMPACT: The conjugated CDCA% in plasma is negatively correlated with biomarkers of RBC oxidative stress in healthy infants. Specific biomarkers of RBC oxidative stress (e.g. MBH, GSH, GSSG) may be promising predictors of conjugated CDCA% in plasma. The type of diet may influence the predictive ability of hit RBC oxidative stress biomarkers (e.g. MBH, GSH, GSSG). Our findings suggest a link between plasma bile acids profile and the RBC redox status in healthy infants, eventually modulated by the type of diet. The recognition of this link may contribute to the development of preventive and therapeutic strategies for neonatal cholestasis.