Limosilactobacillus reuteri Y15 enhances uterine development and function in gilts via the gut-uterus axis

Uterine glands synthesize and secrete compounds essential for embryonic and fetal development. They are critical for pregnancy, and their optimal function enhances prenatal survival and thus increases sow lifetime productivity. The gut microbe-uterus axis plays an important role in uterine development and function. Probiotics, especially Limosilactobacillus reuteri (L. reuteri), have been fed to improve female reproductive function, however, the beneficial effects remain unknow. The current study isolated one native L. reuteri (LRY15) from sow intestines that increased the number of uterine glands, and there elevated the protein expression of an important gene FOXA2. Moreover, LRY15 increased the expression of uterine genes related to angiogenesis, placental development, cell junction proteins, antioxidant enzymes, hormone metabolism, and transcriptional factors. Simultaneously, the protein levels of these factors (including blood vessel markers CD31 and VEGF, and cell junction proteins ZO-1 and occludin) were higher in LRY15 uteri compared to controls. The beneficial blood metabolites such as the tocopherol metabolite, antioxidant metabolites including retinol and the polyunsaturated fatty acids, and the levels of some cholic acids metabolites were elevated in LRY15 gilt blood (P < 0.05). Moreover, LRY15 improved cell-cell junction formation to enhance intestinal function. This is the first report to show that the native probiotic LRY15 can enhance uterine development and function; it is therefore a promising tool for increasing mammalian reproductive capacity in the future.