Bovine milk exosomes supplementation enhances jejunal histological recovery and up-regulates smooth muscle genes in rat offspring following maternal protein malnutrition

Maternal protein malnutrition (PMN) during gestation and lactation severely impairs intestinal growth and development in the offspring. Since bovine milk exosomes (BME) contain important bioactive components with regulatory functions, we evaluated their potential as a nutritional strategy to improve gut health in children exposed to maternal PMN. During gestation and lactation, rats were fed either a PMN diet (8% protein) or an AIN-93G diet (18% protein). After weaning and for 14 days, the offspring from PMN mothers were classified into: the PMN-BME group, which received an AIN-93G diet supplemented with BME, or the PMN-Control group, which received the AIN-93G diet. Offspring from Control mothers continued receiving the AIN-93G diet after weaning (Control group). Intestinal histology and microarray analyses were performed on the offspring. At weaning, maternal PMN reduced intestinal villous length and muscular layer thickness compared to Control group. At 14 days postweaning, BME supplementation improved histological parameters respect to PMN-Control, and restored them to Control levels in the proximal jejunum. In this tissue, BME up-regulated genes encoding myosins involved in smooth muscle function, as well as genes related to smooth muscle structure and extracellular matrix organization. In contrast, the distal jejunum primarily displayed catch-up growth, with both PMN-BME and PMN-Control animals exhibiting up-regulation of genes encoding cytoplasmic ribosomal proteins compared to Control group. BME may represent a promising nutritional strategy to support intestinal recovery after maternal PMN. Offspring supplementation with BME over a short period improved intestinal histological parameters, especially in the proximal jejunum, up-regulating genes associated with extracellular matrix organization and smooth muscle function.