Breastfeeding lifespan control of growth, maintenance, and metabolism of small intestinal epithelium.

Gastrointestinal epithelial cells respond to milk-born molecules throughout breastfeeding, influencing growth, and development. The rapid renewal of the small intestine depends on the proliferation in the crypt that drives cell fates. We used early weaning model to investigate immediate and late effects of breastfeeding on proliferation, differentiation of jejunal epithelial cells. Wistar rats were either allowed to suckle (S) until 21 postnatal days or submitted to early weaning (EW) at 15 days. By comparing ages (18, 60, and 120 days), we found that EW decreased Ki67 indices and villi height at 18 and 60 days (p < 0.05), and at 120 days they were similar between diets. Proliferative reduction and augmented expression of Cdkn1b (p27 gene) were parallel. In the stem cell niche, EW increased the number and activity (Defa24) of Paneth cells at 18 and 60 days (p < 0.05), and Lgr5 and Ascl2 genes showed inverted responses between ages. Among target cells, EW decreased goblet cell number at 18 and 60 days (p < 0.05) and increased it at 120 days (p < 0.05), whereas enteroendocrine marker genes were differentially altered. EW reduced enterocytes density at 18 days (p < 0.05), and at 120 days this population was decreased (vs. 60 days). Among cell fate crypt-controlling genes, Notch and Atoh1 were the main targets of EW. Metabolically, intraperitoneal glucose tolerance was immediately reduced (18 days), being reverted until 120 days (p < 0.05). Currently, we showed that breastfeeding has a lifespan influence on intestinal mucosa and on its stem cell compartment. We suggest that, although jejunum absorptive function is granted after early weaning, the long lasting changes in gene expression might prime the mucosa with a different sensitivity to gut disorders that still have to be further explored.

Colon epithelial cells luminal environment and physiopathological consequences: impact of nutrition and exercise

The colonic epithelial cells represent a border between the colon luminal content, containing notably bacteria and a complex mixture of compounds, and the"milieu interieur"as defined by the French physiologist Claude Bernard.The physical-chemical composition of the luminal content, including luminal pH and bacterial metabolite, that obviousl y is not constant, is modified for instance according to the diet. Data obtained recently indicate that physical exercise may also modify the colonic luminal content. Evidence has indicated that modification of the luminal content characteristics has, indeed, consequences for the colonic epithelial cells, notably in terms of energy metabolism and DNA integrity. Although such alterations impact presumably the homeostatic process of the colonic epithelium renewal and the epithelial barrier function, their contribution to pathological processes like mucosal inflammation, pre-neoplasia, and neoplasia remains partly elusive. Open questions remain regarding the individual and collective roles of luminal changes, particularly in a long-term perspective. These questions are related particularly to the capacity of the bacterial metabolites to cross the mucus layer before entering the colonocytes, to the concentrations of metabolites in proximity of the colonic crypt stem cells, and to the capacity of colonocytes to detoxicate deleterious compounds, to take up and utilize beneficial compounds.