Short-term Administration of Probiotics Promote Protective Immunity Against Enteric Bacteria Infection Through Lgr5+ Stem Cell Differentiation

The probiotics play an indispensable role in gut homeostasis but underlying mechanisms are still unveiled. In order to clarify an exact role of probiotics for protective immunity in the gut, we fed C57BL/6 mice for five days with human-use probiotic Lacidofil® including Lactobacillus (L.) rhamnosus and L. acidophilus and then orally infected with human-specific pathogen such as enterohemorrhagic Escherichia coli O157:H7 (EHEC) strain. For the positive control, mice were treated orally with antibiotics including ampicillin, vancomycin, neomycin, and metronidazole. While oral O157 challenge resulted in severe pathology in the gut such as epithelium shedding and paneth cells distortion in the nil and antibiotic-fed mice group, pre-feeding with Lactobacillus maintained gut normally. We found that significantly lower numbers of bacteria in the gut-associated lymphoid tissues were detected in Lactobacillus-fed mice than those of nil and antibiotics-fed mice at early time post infection. In addition, predominant numbers of activated paneth cells and mucin-secreting goblet cells were found in the probiotics-fed mice when compared with nil and antibiotic-fed mice. Most interestingly, numbers of Lgr5⁺ cells gut stem cells were significantly increase in the crypt regions of Lactobacillus-fed mice than in those of nil and antibiotic-fed mice. Taken together, pre-feeding with probiotic Lactobacillus play a pivotal role to promote gut stem cell differentiation and subsequently to protect host against enteric bacteria infection.