Breastfed infants receiving formula supplementation show altered lipid and gut microbiota profiles at 3 months of age

Pernille Neve Myers; Inge A.L.P. van Beijsterveldt; Stuart G. Snowden; Carsten Eriksen; Henrik Bjørn Nielsen; Ieuan A. Hughes; Ken K. Ong; Anita C.S. Hokken-Koelega; Albert Koulman; Susanne Brix

doi:10.1016/j.clnu.2026.106602

Breastfed infants receiving formula supplementation show altered lipid and gut microbiota profiles at 3 months of age

Pernille Neve Myers
, Inge A.L.P. van Beijsterveldt
, Stuart G. Snowden
, Carsten Eriksen
, Henrik Bjørn Nielsen
, Ieuan A. Hughes
, Ken K. Ong
, Anita C.S. Hokken-Koelega
, Albert Koulman^*
, Susanne Brix^*

^*Corresponding author for this work

Pediatrics

Technical University of Denmark
Cmbio
University of Cambridge
Royal Holloway University of London
MRC Epidemiology Unit

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background & aims:

Exclusive breastfeeding offers numerous health benefits. Despite advancements in formula, significant differences compared with breast milk remain. We aimed to assess how milk feeding type and volume at 3 months affect the infant plasma lipidome and gut microbiota.

Methods:

Infants were classified into exclusive breastfeeding (EBF), mixed feeding (MF), or exclusive formula feeding (EFF) groups based on feeding data collected prospectively across two European cohorts (n = 519). Lipidomics and shotgun metagenomics were applied to plasma and stool samples, respectively.

Results:

Feeding type explained major variation in both lipidomic and microbial profiles. Plasma lipids showed distinct signatures across groups, particularly in sphingomyelins and diacylglycerols. Microbiota diversity and species richness increased with formula exposure. Formula rich in intact whey protein was linked to higher S. thermophilus abundance in the infant gut. Random forest classification of feeding type using either lipidomic or gut microbiota features achieved high discriminatory accuracy (AUROC >0.90) in training and validation datasets.

Conclusion:

Early nutrition is a critical determinant of the lipidome and gut microbiome during the breastfeeding phase.

Original language	English
Article number	106602
Journal	Clinical Nutrition
Volume	59
DOIs	https://doi.org/10.1016/j.clnu.2026.106602
Publication status	Published - Apr 2026

Bibliographical note

Publisher Copyright:
© 2026 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

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Breastfed infants receiving formula supplementation show altered lipid and gut microbiota profiles at 3 months of ageFinal published version, 2.57 MBLicence: CC BY

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Myers, P. N., van Beijsterveldt, I. A. L. P., Snowden, S. G., Eriksen, C., Nielsen, H. B., Hughes, I. A., Ong, K. K., Hokken-Koelega, A. C. S., Koulman, A., & Brix, S. (2026). Breastfed infants receiving formula supplementation show altered lipid and gut microbiota profiles at 3 months of age. Clinical Nutrition, 59, Article 106602. https://doi.org/10.1016/j.clnu.2026.106602

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title = "Breastfed infants receiving formula supplementation show altered lipid and gut microbiota profiles at 3 months of age",

abstract = "Background \& aims: Exclusive breastfeeding offers numerous health benefits. Despite advancements in formula, significant differences compared with breast milk remain. We aimed to assess how milk feeding type and volume at 3 months affect the infant plasma lipidome and gut microbiota. Methods: Infants were classified into exclusive breastfeeding (EBF), mixed feeding (MF), or exclusive formula feeding (EFF) groups based on feeding data collected prospectively across two European cohorts (n = 519). Lipidomics and shotgun metagenomics were applied to plasma and stool samples, respectively. Results: Feeding type explained major variation in both lipidomic and microbial profiles. Plasma lipids showed distinct signatures across groups, particularly in sphingomyelins and diacylglycerols. Microbiota diversity and species richness increased with formula exposure. Formula rich in intact whey protein was linked to higher S. thermophilus abundance in the infant gut. Random forest classification of feeding type using either lipidomic or gut microbiota features achieved high discriminatory accuracy (AUROC >0.90) in training and validation datasets. Conclusion:Early nutrition is a critical determinant of the lipidome and gut microbiome during the breastfeeding phase.",

author = "Myers, \{Pernille Neve\} and \{van Beijsterveldt\}, \{Inge A.L.P.\} and Snowden, \{Stuart G.\} and Carsten Eriksen and Nielsen, \{Henrik Bj{\o}rn\} and Hughes, \{Ieuan A.\} and Ong, \{Ken K.\} and Hokken-Koelega, \{Anita C.S.\} and Albert Koulman and Susanne Brix",

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/",

year = "2026",

month = apr,

doi = "10.1016/j.clnu.2026.106602",

language = "English",

volume = "59",

journal = "Clinical Nutrition",

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AU - Myers, Pernille Neve

AU - van Beijsterveldt, Inge A.L.P.

AU - Snowden, Stuart G.

AU - Eriksen, Carsten

AU - Nielsen, Henrik Bjørn

AU - Hughes, Ieuan A.

AU - Ong, Ken K.

AU - Hokken-Koelega, Anita C.S.

AU - Koulman, Albert

AU - Brix, Susanne

PY - 2026/4

Y1 - 2026/4

N2 - Background & aims: Exclusive breastfeeding offers numerous health benefits. Despite advancements in formula, significant differences compared with breast milk remain. We aimed to assess how milk feeding type and volume at 3 months affect the infant plasma lipidome and gut microbiota. Methods: Infants were classified into exclusive breastfeeding (EBF), mixed feeding (MF), or exclusive formula feeding (EFF) groups based on feeding data collected prospectively across two European cohorts (n = 519). Lipidomics and shotgun metagenomics were applied to plasma and stool samples, respectively. Results: Feeding type explained major variation in both lipidomic and microbial profiles. Plasma lipids showed distinct signatures across groups, particularly in sphingomyelins and diacylglycerols. Microbiota diversity and species richness increased with formula exposure. Formula rich in intact whey protein was linked to higher S. thermophilus abundance in the infant gut. Random forest classification of feeding type using either lipidomic or gut microbiota features achieved high discriminatory accuracy (AUROC >0.90) in training and validation datasets. Conclusion:Early nutrition is a critical determinant of the lipidome and gut microbiome during the breastfeeding phase.

AB - Background & aims: Exclusive breastfeeding offers numerous health benefits. Despite advancements in formula, significant differences compared with breast milk remain. We aimed to assess how milk feeding type and volume at 3 months affect the infant plasma lipidome and gut microbiota. Methods: Infants were classified into exclusive breastfeeding (EBF), mixed feeding (MF), or exclusive formula feeding (EFF) groups based on feeding data collected prospectively across two European cohorts (n = 519). Lipidomics and shotgun metagenomics were applied to plasma and stool samples, respectively. Results: Feeding type explained major variation in both lipidomic and microbial profiles. Plasma lipids showed distinct signatures across groups, particularly in sphingomyelins and diacylglycerols. Microbiota diversity and species richness increased with formula exposure. Formula rich in intact whey protein was linked to higher S. thermophilus abundance in the infant gut. Random forest classification of feeding type using either lipidomic or gut microbiota features achieved high discriminatory accuracy (AUROC >0.90) in training and validation datasets. Conclusion:Early nutrition is a critical determinant of the lipidome and gut microbiome during the breastfeeding phase.

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VL - 59

JO - Clinical Nutrition

JF - Clinical Nutrition

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ER -

Breastfed infants receiving formula supplementation show altered lipid and gut microbiota profiles at 3 months of age

Abstract

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