TY - JOUR
T1 - Interactions between Bifidobacterium and Bacteroides and human milk oligosaccharides and their associations with infant cognition
AU - Cho, Seoyoon
AU - Samuel, Tinu M.
AU - Li, Tengfei
AU - Howell, Brittany R.
AU - Baluyot, Kristine
AU - Hazlett, Heather C.
AU - Elison, Jed T.
AU - Zhu, Hongtu
AU - Hauser, Jonas
AU - Sprenger, Norbert
AU - Lin, Weili
N1 - Publisher Copyright:
Copyright © 2023 Cho, Samuel, Li, Howell, Baluyot, Hazlett, Elison, Zhu, Hauser, Sprenger and Lin.
PY - 2023
Y1 - 2023
N2 - While ample research on independent associations between infant cognition and gut microbiota composition and human milk (HM) oligosaccharides (HMOs) has been reported, studies on how the interactions between gut microbiota and HMOs may yield associations with cognitive development in infancy are lacking. We aimed to determine how HMOs and species of Bacteroides and Bifidobacterium genera interact with each other and their associations with cognitive development in typically developing infants. A total of 105 mother-infant dyads were included in this study. The enrolled infants [2.9–12 months old (8.09 ± 2.48)] were at least predominantly breastfed at 4 months old. A total of 170 HM samples from the mothers and fecal samples of the children were collected longitudinally. Using the Mullen Scales of Early Learning to assess cognition and the scores as the outcomes, linear mixed effects models including both the levels of eight HMOs and relative abundance of Bacteroides and Bifidobacterium species as main associations and their interactions were employed with adjusting covariates; infant sex, delivery mode, maternal education, site, and batch effects of HMOs. Additionally, regression models stratifying infants based on the A-tetrasaccharide (A-tetra) status of the HM they received were also employed to determine if the associations depend on the A-tetra status. With Bacteroides species, we observed significant associations with motor functions, while Bif. catenulatum showed a negative association with visual reception in the detectable A-tetra group both as main effect (value of p = 0.012) and in interaction with LNFP-I (value of p = 0.007). Additionally, 3-FL showed a positive association with gross motor (p = 0.027) and visual reception (p = 0.041). Furthermore, significant associations were observed with the interaction terms mainly in the undetectable A-tetra group. Specifically, we observed negative associations for Bifidobacterium species and LNT [breve (p = 0.011) and longum (p = 0.022)], and positive associations for expressive language with 3′-SL and Bif. bifidum (p = 0.01), 6′-SL and B. fragilis (p = 0.019), and LNFP-I and Bif. kashiwanohense (p = 0.048), respectively. Our findings suggest that gut microbiota and HMOs are both independently and interactively associated with early cognitive development. In particular, the diverse interactions between HMOs and Bacteroides and Bifidobacterium species reveal different candidate pathways through which HMOs, Bifidobacterium and Bacteroides species potentially interact to impact cognitive development in infancy.
AB - While ample research on independent associations between infant cognition and gut microbiota composition and human milk (HM) oligosaccharides (HMOs) has been reported, studies on how the interactions between gut microbiota and HMOs may yield associations with cognitive development in infancy are lacking. We aimed to determine how HMOs and species of Bacteroides and Bifidobacterium genera interact with each other and their associations with cognitive development in typically developing infants. A total of 105 mother-infant dyads were included in this study. The enrolled infants [2.9–12 months old (8.09 ± 2.48)] were at least predominantly breastfed at 4 months old. A total of 170 HM samples from the mothers and fecal samples of the children were collected longitudinally. Using the Mullen Scales of Early Learning to assess cognition and the scores as the outcomes, linear mixed effects models including both the levels of eight HMOs and relative abundance of Bacteroides and Bifidobacterium species as main associations and their interactions were employed with adjusting covariates; infant sex, delivery mode, maternal education, site, and batch effects of HMOs. Additionally, regression models stratifying infants based on the A-tetrasaccharide (A-tetra) status of the HM they received were also employed to determine if the associations depend on the A-tetra status. With Bacteroides species, we observed significant associations with motor functions, while Bif. catenulatum showed a negative association with visual reception in the detectable A-tetra group both as main effect (value of p = 0.012) and in interaction with LNFP-I (value of p = 0.007). Additionally, 3-FL showed a positive association with gross motor (p = 0.027) and visual reception (p = 0.041). Furthermore, significant associations were observed with the interaction terms mainly in the undetectable A-tetra group. Specifically, we observed negative associations for Bifidobacterium species and LNT [breve (p = 0.011) and longum (p = 0.022)], and positive associations for expressive language with 3′-SL and Bif. bifidum (p = 0.01), 6′-SL and B. fragilis (p = 0.019), and LNFP-I and Bif. kashiwanohense (p = 0.048), respectively. Our findings suggest that gut microbiota and HMOs are both independently and interactively associated with early cognitive development. In particular, the diverse interactions between HMOs and Bacteroides and Bifidobacterium species reveal different candidate pathways through which HMOs, Bifidobacterium and Bacteroides species potentially interact to impact cognitive development in infancy.
KW - Mullen Scales of Early Learning
KW - early cognitive development
KW - group lasso
KW - human milk
KW - human milk oligosaccharides
KW - infant gut microbiota
KW - random linear mixed effects model
UR - http://www.scopus.com/inward/record.url?scp=85165087236&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85165087236&partnerID=8YFLogxK
U2 - 10.3389/fnut.2023.1216327
DO - 10.3389/fnut.2023.1216327
M3 - Article
C2 - 37457984
AN - SCOPUS:85165087236
SN - 2296-861X
VL - 10
JO - Frontiers in Nutrition
JF - Frontiers in Nutrition
M1 - 1216327
ER -