Specific Milk Composition of miR-30b Transgenic Mice Associated with Early Duodenum Maturation in Offspring with Lasting Consequences for Growth

Sandrine Le Guillou; Céline Ciobotaru; Johann Laubier; Johan Castille; Etienne Aujean; Cathy Hue-Beauvais; Claire Cherbuy; Sophie Liuu; Céline Henry; Agnès David; Florence Jaffrezic; Denis Laloë; Madia Charlier; Marie-Cécile Alexandre-Gouabau; Fabienne Le Provost

doi:10.1016/j.tjnut.2023.08.003

Specific Milk Composition of miR-30b Transgenic Mice Associated with Early Duodenum Maturation in Offspring with Lasting Consequences for Growth

J Nutr. 2023 Oct;153(10):2808-2826. doi: 10.1016/j.tjnut.2023.08.003. Epub 2023 Aug 4.

Authors

Affiliations

¹ Université Paris-Saclay, INRAE, AgroParisTech, GABI, Jouy-en-Josas, France. Electronic address: sandrine.le-guillou@inrae.fr.
² Université Paris-Saclay, INRAE, AgroParisTech, GABI, Jouy-en-Josas, France.
³ Université Paris-Saclay, INRAE, MICALIS Institute, Jouy-en-Josas, France.
⁴ Université Paris-Saclay, INRAE, AgroParisTech, MICALIS Institute, PAPPSO, Jouy-en-Josas, France.
⁵ Nantes Université, CRNH-OUEST, INRAE, UMR 1280, PhAN, Nantes, France.

PMID: 37543213
DOI: 10.1016/j.tjnut.2023.08.003

Abstract

Background: Milk composition is complex and includes numerous components essential for offspring growth and development. In addition to the high abundance of miR-30b microRNA, milk produced by the transgenic mouse model of miR-30b-mammary deregulation displays a significantly altered fatty acid profile. Moreover, wild-type adopted pups fed miR-30b milk present an early growth defect.

Objective: This study aimed to investigate the consequences of miR-30b milk feeding on the duodenal development of wild-type neonates, a prime target of suckled milk, along with comprehensive milk phenotyping.

Methods: The duodenums of wild-type pups fed miR-30b milk were extensively characterized at postnatal day (PND)-5, PND-6, and PND-15 using histological, transcriptomic, proteomic, and duodenal permeability analyses and compared with those of pups fed wild-type milk. Milk of miR-30b foster dams collected at mid-lactation was extensively analyzed using proteomic, metabolomic, and lipidomic approaches and hormonal immunoassays.

Results: At PND-5, wild-type pups fed miR-30b milk showed maturation of their duodenum with 1.5-fold (P < 0.05) and 1.3-fold (P < 0.10) increased expression of Claudin-3 and Claudin-4, respectively, and changes in 8 duodenal proteins (P < 0.10), with an earlier reduction in paracellular and transcellular permeability (183 ng/mL fluorescein sulfonic acid [FSA] and 12 ng/mL horseradish peroxidase [HRP], respectively, compared with 5700 ng/mL FSA and 90 ng/mL HRP in wild-type; P < 0.001). Compared with wild-type milk, miR-30b milk displayed an increase in total lipid (219 g/L compared with 151 g/L; P < 0.05), ceramide (17.6 μM compared with 6.9 μM; P < 0.05), and sphingomyelin concentrations (163.7 μM compared with 76.3 μM; P < 0.05); overexpression of 9 proteins involved in the gut barrier (P < 0.1); and higher insulin and leptin concentrations (1.88 ng/mL and 2.04 ng/mL, respectively, compared with 0.79 ng/mL and 1.06 ng/mL; P < 0.01).

Conclusions: miR-30b milk displays significant changes in bioactive components associated with neonatal duodenal integrity and maturation, which could be involved in the earlier intestinal closure phenotype of the wild-type pups associated with a lower growth rate.

Keywords: early maturation; intestinal barrier; miR-30b; mice; milk composition.