TY - JOUR
T1 - Absolute quantification of eight human milk oligosaccharides in breast milk to evaluate their concentration profiles and associations with infants’ neurodevelopmental outcomes
AU - Sato, Keigo
AU - Nakamura, Yoshitaka
AU - Fujiyama, Kazuhito
AU - Ohneda, Kinuko
AU - Nobukuni, Takahiro
AU - Ogishima, Soichi
AU - Mizuno, Satoshi
AU - Koshiba, Seizo
AU - Kuriyama, Shinichi
AU - Jinno, Shinji
N1 - Publisher Copyright:
© 2024 The Author(s). Journal of Food Science published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.
PY - 2024/12
Y1 - 2024/12
N2 - Human milk oligosaccharides (HMOs) have been positively associated with child neurodevelopment in some cohort studies. However, there is a lack of consistency in the association between HMOs and benefits to infants’ brains. Moreover, the quantification methods for HMOs have not yet been standardized. In this study, we developed a quantification method for evaluating eight HMOs (2′-fucosyllactose [2′-FL], 3′-fucosyllactose [3′-FL], 3′-sialyllactose [3′-SL], 6′-sialyllactose [6′-SL], lactosialyltetrasaccharide a [LSTa], lactosialyltetrasaccharide b [LSTb], lactosialyltetrasaccharide c [LSTc], and disialyllacto-N-tetraose [DSLNT]) in breast milk. After validating the method, we applied it to 1-month breast milk samples (n = 150) from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study to assess HMO profiles in breast milk and their possible association with changes in head circumference z-score (ΔHCZ) and neurodevelopmental scores of children (as measured by the Ages and Stages Questionnaire, Third Edition). The validation demonstrated that the method had relative standard deviation ≤ 12.7% of precision and 79.5–110.9% of accuracy. Using this method, eight HMO levels (2′-FL, 0–4.74 mg/mL; 3′-FL, 0.02–1.52 mg/mL; 3′-SL, 0.07–0.32 mg/mL; 6′-SL, 0.01–0.70 mg/mL; LSTa, 0.002–0.043 mg/mL; LSTb, 0.02–0.31 mg/mL; LSTc, 0.001–0.47 mg/mL; and DSLNT, 0.09–0.71 mg/mL [min–max, all participants]) and the ratio of low secretors (16.0%) in the Japanese cohort were obtained. The obtained HMO levels in breast milk were subjected to multivariate analysis to screen for HMOs showing a positive association with ΔHCZ and neurodevelopmental scores. The results proposed that ΔHCZ was positively associated with LSTb and 2′-FL levels, whereas neurodevelopmental scores were positively associated with 2′-FL levels (among all participants) and 3′-SL and DSLNT levels (among secretor participants). This study showed that the developed method provides HMO profiles in Japanese breast milk, as well as additional information on the associations between specific HMOs and neurodevelopment, reinforcing the sum of evidence for the role of HMOs in the brain.
AB - Human milk oligosaccharides (HMOs) have been positively associated with child neurodevelopment in some cohort studies. However, there is a lack of consistency in the association between HMOs and benefits to infants’ brains. Moreover, the quantification methods for HMOs have not yet been standardized. In this study, we developed a quantification method for evaluating eight HMOs (2′-fucosyllactose [2′-FL], 3′-fucosyllactose [3′-FL], 3′-sialyllactose [3′-SL], 6′-sialyllactose [6′-SL], lactosialyltetrasaccharide a [LSTa], lactosialyltetrasaccharide b [LSTb], lactosialyltetrasaccharide c [LSTc], and disialyllacto-N-tetraose [DSLNT]) in breast milk. After validating the method, we applied it to 1-month breast milk samples (n = 150) from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study to assess HMO profiles in breast milk and their possible association with changes in head circumference z-score (ΔHCZ) and neurodevelopmental scores of children (as measured by the Ages and Stages Questionnaire, Third Edition). The validation demonstrated that the method had relative standard deviation ≤ 12.7% of precision and 79.5–110.9% of accuracy. Using this method, eight HMO levels (2′-FL, 0–4.74 mg/mL; 3′-FL, 0.02–1.52 mg/mL; 3′-SL, 0.07–0.32 mg/mL; 6′-SL, 0.01–0.70 mg/mL; LSTa, 0.002–0.043 mg/mL; LSTb, 0.02–0.31 mg/mL; LSTc, 0.001–0.47 mg/mL; and DSLNT, 0.09–0.71 mg/mL [min–max, all participants]) and the ratio of low secretors (16.0%) in the Japanese cohort were obtained. The obtained HMO levels in breast milk were subjected to multivariate analysis to screen for HMOs showing a positive association with ΔHCZ and neurodevelopmental scores. The results proposed that ΔHCZ was positively associated with LSTb and 2′-FL levels, whereas neurodevelopmental scores were positively associated with 2′-FL levels (among all participants) and 3′-SL and DSLNT levels (among secretor participants). This study showed that the developed method provides HMO profiles in Japanese breast milk, as well as additional information on the associations between specific HMOs and neurodevelopment, reinforcing the sum of evidence for the role of HMOs in the brain.
KW - breast milk
KW - head growth
KW - human milk oligosaccharides
KW - infants
KW - neurodevelopment
UR - http://www.scopus.com/inward/record.url?scp=85211496804&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85211496804&partnerID=8YFLogxK
U2 - 10.1111/1750-3841.17597
DO - 10.1111/1750-3841.17597
M3 - Article
C2 - 39656795
AN - SCOPUS:85211496804
SN - 0022-1147
VL - 89
SP - 10152
EP - 10170
JO - Journal of Food Science
JF - Journal of Food Science
IS - 12
ER -