Prebiotic Activity of Vaginal Lactobacilli on Bifidobacteria: from Concept to Formulation

The gut of babies born vaginally is rapidly colonized by Bifidobacterium spp. after birth, while in infants born by cesarean section (C-section), the presence of bifidobacteria drops dramatically, increasing the risk of developing gastrointestinal disorders. Considering that newborns naturally come into contact with maternal lactobacilli as they pass through the birth canal, the aim of this work is to exploit for the first time the bifidogenic activity exerted by the cell-free supernatants (CFSs) from lactobacilli of vaginal origin, belonging to the species Lactobacillus crispatus, Lactobacillus gasseri, Limosilactobacillus vaginalis, and Lactiplantibacillus plantarum. CFSs were recovered after 7 h, 13 h, and 24 h of fermentation and assessed for the ability to stimulate the planktonic growth and biofilms of Bifidobacterium strains belonging to species widely represented in the gut tract. A bifidogenic effect was observed for all CFSs; such activity was maximal for CFSs recovered in exponential phase and was strongly dependent on the species of lactobacilli. Importantly, no stimulating effects on an intestinal Escherichia coli strain were observed. CFSs from L. vaginalis BC17 showed the best bifidogenic profile since they increased bifidobacterial planktonic growth by up to 432% and biofilm formation by up to 289%. The CFS at 7 h from BC17 was successfully formulated with a hyaluronic acid-based hydrogel aimed at preventing and treating breast sores in lactating women and exerting bifidogenic activity in infants born mainly by C-section. IMPORTANCE Bifidobacteria in the gut tract of infants play crucial roles in the prevention of gastrointestinal diseases and the maturation of the immune system. Consequently, strategies to trigger a bifidogenic shift in the infant gut are highly desirable. Evidences suggest that the presence of a maternal vaginal microbiota dominated by health-promoting lactobacilli and the development of a bifidobacterium-enriched gut microbiota in newborns are interconnected. In this context, we found out that the cell-free supernatants from lactobacilli of vaginal origin were able to effectively stimulate the proliferation of Bifidobacterium spp. grown in free-floating and biofilm forms. The cell-free supernatant from Limosilactobacillus vaginalis BC17 showed excellent bifidogenic behavior, which was preserved even after its incorporation into a nipple formulation for lactating women. Lactobacilli derivatives, such as cell-free supernatants, have gained increasing interest by virtue of their safer profile than that of living cells and can be proposed as an ecosustainable approach to favor gut colonization of infants by bifidobacteria.