Tsg101 knockout in the mammary gland leads to a decrease in small extracellular vesicles in milk from C57BL/6J dams and contributes to leakiness of the gut mucosa and reduced postnatal weight gain in suckling pups.

Autor: Munir J; Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA., Sadri M; Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA., Zempleni J; Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA. Electronic address: jzempleni2@unl.edu.
Jazyk: angličtina
Zdroj: The Journal of nutritional biochemistry [J Nutr Biochem] 2025 Jan; Vol. 135, pp. 109782. Date of Electronic Publication: 2024 Oct 17.
DOI: 10.1016/j.jnutbio.2024.109782
Abstrakt: Human milk contains 2.2 ± 1.5×10 11 small extracellular vesicles (sEVs) per milliliter and human infants consume 1.7×10 14 milk sEVs (sMEVs) daily in 800 mL milk. Infant formula contains trace amounts of sMEVs. To date, eight adverse effects of milk depletion and five beneficial effects of sMEV supplementation have been reported including studies in infants and neonate mice. Formula-fed infants do not realize the benefits of sMEVs. Most of the phenotyping studies reported to date have the limitation that sMEV depletion and supplementation were initiated after mice were weaned. Here, we used a genetics approach for assessing effects of sMEV depletion on the development of suckling mice. Newborn C57BL/6J pups were fostered to Tumor Susceptibility Gene 101 (Tsg101) mammary-specific knockout (KO) dams or C57BL/6J dams (controls) in synchronized pregnancies. Tsg101 KO was associated with an 80% decrease of sMEVs. Postnatal weight gain and gut health (histology, morphology, and barrier function) were assessed until weaning at age three weeks. We observed a significant decrease in weight gain, length of small intestine, villi height, crypt depth, and intestinal barrier function in male and female pups fostered to Tsg101 dams compared to pups fostered to control dams. The effect size varied between 11 and 32 percent. Maternal Tsg101 KO did not affect the dams' health, content of macronutrients and dry mass of milk and had no effect on the amount of milk consumed by pups. We conclude that sMEVs are important for growth and gut health in neonate mice.
Competing Interests: Declaration of competing interests The authors declare no conflict of interest. J. Zempleni serves as an editorial board member for the Journal of Nutritional Biochemistry and other scientific journals, and his research is currently funded by the National Institutes of Health, the National Institute of Food and Agriculture, and the Syngap Research Fund.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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