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REVIEW article

Front. Nutr.

Sec. Nutrition and Metabolism

Volume 12 - 2025 | doi: 10.3389/fnut.2025.1635919

This article is part of the Research TopicHuman Milk, Nutrition and Infant Development, Volume IIView all 12 articles

Human milk vs. cow-milk based infant formula proteins: structure, digestion and physiological impacts

Provisionally accepted
Lucile  Chauvet Ab#Lucile Chauvet Ab#1Elise  Charton Ab#Elise Charton Ab#2Marion  LemaireMarion Lemaire3Amélie  DeglaireAmélie Deglaire1,2Isabelle  Le Huërou-LuronIsabelle Le Huërou-Luron1*
  • 1Human Nutrition, INRA Centre Bretagne-Normandie, Rennes, France
  • 2L'Institut Agro Rennes-Angers, Rennes, France
  • 3Sodiaal International, Rennes, France

The final, formatted version of the article will be published soon.

This review examines the differences in protein composition, digestion, and physiological effects on infants between human milk (HM) and infant formula (IF). The World Health Organization recommends exclusive breastfeeding for the first six months of life due to the numerous health benefits associated with it. However, when this is not possible, IF is used as an alternative. Differences between HM and IF remain, particularly in terms of protein composition and structure. Further optimization of IF is needed to better mimic HM and provide similar health benefits. Further improving IF formulation requires implementing a promising strategy, which in turn requires a thorough understanding of the mechanisms of protein digestion and amino acid (AA) absorption, as well as the metabolic and physiological effects of protein composition and structure. These are often altered by heat treatment and processing in IF.The main differences in the protein composition and structure of HM and IF are presented, including a synthesis of knowledge on the non-protein nitrogen (NPN) fraction. This fraction is too often neglected in milks, despite accounting for one fifth of the total nitrogen in HM. The influence of the protein composition and structure of HM and IF on the digestion of dietary protein and dietary AA absorption is compared, highlighting the need for data on the postprandial AA profile in infants from well-designed clinical trials. Finally, this review examines the differences in protein composition and digestion between HM and IF that lead to distinct metabolic, physiological and microbial outcomes. Future research should focus on understanding the role of partially digested proteins and the NPN fraction in shaping the infant gut microbiota and overall health.

Keywords: Milk protein, protein structure, Non-protein nitrogen (NPN), Digestion, Plasma amino acid, Gut Microbiota, Gut physiology, Metabolism

Received: 27 May 2025; Accepted: 21 Jul 2025.

Copyright: © 2025 Chauvet Ab#, Charton Ab#, Lemaire, Deglaire and Le Huërou-Luron. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Isabelle Le Huërou-Luron, Human Nutrition, INRA Centre Bretagne-Normandie, Rennes, 35590, France

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