CE21 - Alimentation et systèmes alimentaires

Treatment of breast milk by high-pressure processing increases its biological and intestinotropic properties: experimental and clinical studies in preterm newborns. – HHP-humanmilk

High pressure processing and human milk

High pressure processing protects bioactive compounds of human milk and its intestrophic properties

Demonstrate the preservation of bioactive compounds in human milk after HHP

1 / to determine if the HHP process improves the quality of LM in terms of very sensitive bioactive factors (growth factors, hormones, microRNAs and bacteriostatic factors) compared to Holder pasteurization; 2 / to study whether this treatment of LM increases its intestino-trophic properties in an experimental ex-vivo model of gastrointestinal maturation; 3 / to study in vivo in newborns whether this milk treated with HHP improves neonatal health, the implantation of the intestinal microbiota and early postnatal growth over a period of 21 days

ELISAs, qRT-PCR, microArrays, Mass spectrometry, ex-vivo and in vivo experiments in mice

To date, we have demonstrated that HHP protects breast milk hormones, its oligosaccharides and its microRNAs. Ex-vivo and in-vivo studies will strengthen these data. The microbiological quality of the processed milk is very good and comparable to Holder pasteurization. Milk treated with HHP remains sterile at 4 ° C for 6 months.

To date, we have shown that treatment with HHP greatly improves the quality of pasteurized breast milk in human milk banks. This innovative technique could eventually replace the Pasteurization by Holder used in HMBs, which unfortunately destroys many important bioactive factors of HM intended for premature children. Thus, we observed that HHP protects milk hormones (article 1), oligosaccharides (article 2), its bacteriostatic capacities (article 3) and its microRNAs (article 4). All of these components are important for the health of newborns. We will measure the antioxidant capacities, vitamins and lipids, glycation products which could also be improved. Our innovative ex-vivo model is also ready to study the ex-vivo intestino-trophic actions of treated HM.

High hydrostatic pressure processing of human milk preserves milk oligosaccharides and avoids formation of Maillard reaction products. Clinical Nutrition, 2022, 41 (1), pp.1 - 8. ?10.1016/j.clnu.2021.11.013?. ?hal-03890167?
In Vivo Assessment of Antioxidant Potential of Human Milk Treated by Holder Pasteurization or High Hydrostatic Pressure Processing: A Preliminary Study on Intestinal and Hepatic Markers in Adult Mice. Antioxidants , 2022, 11 (6), pp.1091. ?10.3390/antiox11061091?. ?hal-03890146?
High Hydrostatic Pressure Processing of Human Milk Increases Apelin and GLP-1 Contents to Modulate Gut Contraction and Glucose Metabolism in Mice Compared to Holder Pasteurization. Nutrients, 2022, 14 (1), pp.219. ?10.3390/nu14010219?. ?hal-03890156?

Breast milk is a unique source of nutritional and bioactive substances essential to the development of immune and digestive systems of the newborn. Its beneficial effects on development and health are especially important in preterm newborns for whom many studies have demonstrated that breast milk significantly reduces the risk of several diseases including digestive intolerance, ulcerative necrotizing enterocolitis (NEC), sepsis, and food allergy. In addition, breast milk has shown long-term positive effects on cognitive development and metabolism and cardiovascular health in adult.
During their hospital stay, preterm infants receive pooled human milk (HM) from different donors provided by human milk bank (HMB). However, HM needs to be treated in order to limit the development of potentially pathogenic agents, whilst retaining its nutritional and immunomodulatory properties. The most common practice performed in HMBs worldwide to treat HM is a low-temperature (62°C) long-time (30 minutes) pasteurization known as “Holder” pasteurization. However, Holder pasteurization performed in HMB completely destroys important milk factors such as the bile salt-stimulated lipase (BSSL), alters milk fat globules structures and reduces both the nutritional value and immunological properties of HM. High hydrostatic pressure (HHP) processing is a recent technology in the food industry that applies a non-thermal high pressure treatment to the product. This new process is one of the most promising methods for food treatment and preservation at room temperature. For HM, HHP is a promising alternative method to Holder pasteurization as several studies have demonstrated that HHP preserves milk nutritional and immunological properties and inactivate microorganisms. Our objectives will be divided into 3 points: 1/ to determine if HHP process improve milk quality in term of sensitive bioactive factors (growth factors, hormones, microRNAs and bacteriostatic properties) compared to Holder pasteurization; 2/ to study experimentally if HHP-treated HM possesses more potent intestinotropic properties than pasteurized HM; 3/ to study in preterm infants, if HHP-treated HM improve the neonatal health, gut microbiome and the early postnatal growth of these infants compared to infants fed with pasteurized HM during 21 days. Our strong consortium implicate recognized scientists (INSERM, Universities, Hospital) specialized in the field of neonatal physiology, a private French partner HPBioTech (AP) that has an international patent for HHP-treated human milk, recognized clinical experts in infant nutrition and recognized experts in the field of gut microbiota. All of these partners have complementary skills to carry out the various tasks to support the present project and have national and international recognition in their respective fields. The clinical study will be performed in the Jeanne de Flandre hospital of the CHRU of Lille. To conclude, providing an alternative to Holder pasteurization with better performance in regard of microbiological safety, nutritional and biological components would be a major step forward including but not limited to the French population of preterm and low birth weight infants. Moreover, our project may have a good economic impact for HMBs as HPP may improve the safety of human milk (microorganism), reduce losses (pasteurization failure) and improve storage and transportation of treated-HM (4°C instead of -20°C). It may also permit to better understand the establishement of gut microbiota associated with breastmilk components.

Project coordination

Jean LESAGE (Institute for Translational Research in Inflammation)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


INFINITE Institute for Translational Research in Inflammation
IRSD Institut de Recherche en Santé Digestive
INFINITE Institute for Translational Research in Inflammation

Help of the ANR 419,580 euros
Beginning and duration of the scientific project: December 2018 - 36 Months

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