BackgroundCommensal-derived probiotic bacteria inhibit enteric pathogens and regulate host immune responses in the gastrointestinal tract, but studies examining specific functions of beneficial microbes in the context of biofilms have been limited in scope.ResultsLactobacillus reuteri formed biofilms that retained functions potentially advantageous to the host including modulation of cytokine output and the production of the antimicrobial agent, reuterin. Immunomodulatory activities of biofilms were demonstrated by the abilities of specific L. reuteri strains to suppress human TNF production by LPS-activated monocytoid cells. Quantification of the antimicrobial glycerol derivative, reuterin, was assessed in order to document the antipathogenic potential of probiotic biofilms. L. reuteri biofilms differed in the quantities of reuterin secreted in this physiological state.ConclusionL. reuteri biofilms secreted factors that confer specific health benefits such as immunomodulation and pathogen inhibition. Future probiotic selection strategies should consider a strain's ability to perform beneficial functions as a biofilm.
Host inflammatory responses against pathogenic organisms can be abrogated by commensals; however, the molecular mechanisms by which pathogenesis is prevented are still poorly understood. Previous studies demonstrated that administration of a single dose of Bacillus subtilis prevented disease and inflammation by the enteric mouse pathogen Citrobacter rodentium, which causes disease similar to the human pathogen enteropathogenic E. coli. No protection was observed when an exopolysaccharide (EPS)-deficient mutant of B. subtilis was used, suggesting that EPS are the protective factor. Here, we isolated and characterized EPS, and showed that they also prevent C. rodentium-associated intestinal disease after a single injection. Protection is TLR4-dependent, since EPS-treated TLR4 KO mice developed disease. Further, protection could be conveyed to wild-type (wt) mice by adoptive transfer of macrophage-rich peritoneal cells from EPS-treated mice. We found that EPS specifically bind peritoneal macrophages and because mice lacking MyD88 signaling in myeloid cells were not protected by EPS, we conclude that bacterial EPS prevent colitis in a TLR4-dependent manner that requires myeloid cells. These studies provide a simple means of preventing intestinal inflammation caused by enteric pathogens.
Clostridium difficile infection (CDI) is a major cause of health care-associated disease. CDI initiates with ingestion of C. difficile spores, germination in the gastrointestinal (GI) tract, and then colonization of the large intestine. The interactions between C. difficile cells and other bacteria and with host mucosa during CDI remain poorly understood. Here, we addressed the hypothesis that, in a mouse model of CDI, C. difficile resides in multicellular communities (biofilms) in association with host mucosa. To do this, we paraffin embedded and then sectioned the GI tracts of infected mice at various days postinfection (p.i.). We then used fluorescent in situ hybridization (FISH) with 16S rRNA probes targeting most bacteria as well as C. difficile specifically. The results revealed that C. difficile is present as a minority member of communities in the outer (loose) mucus layer, in the cecum and colon, starting at day 1 p.i. To generate FISH probes that identify bacteria within mucus-associated communities harboring C. difficile, we characterized bacterial populations in the infected mouse GI tract using 16S rRNA gene sequence analysis of bacterial DNA prepared from intestinal content. This analysis revealed the presence of genera of several families belonging to Bacteroidetes and Firmicutes. These data suggest that formation of multispecies communities associated with the mucus of the cecum and colon is an important early step in GI tract colonization. They raise the possibility that other bacterial species in these communities modulate the ability of C. difficile to successfully colonize and, thereby, cause disease.
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