| Probiotics are live microorganisms, which when administered in adequate amounts, confer a health benefit on the host. Lactobacillus casei is a probiotic species of particular interest due to it being commonly consumed worldwide as a probiotic. Significant genetic variation exists between L. casei strains, with 32-45% of the genome-content being variable. Therefore, strain-to-strain differences in their probiotic efficacy are likely. This dissertation describes the use of L. casei strains to modulate the gut microbiota and immune function; additionally L. casei strains were functionally and genomically examined to unravel their probiotic mechanisms of action. First study demonstrated that L. casei 32G administration modified the cecum-microbiota in a dose and time dependent manner. An increase in prevalence of Lactobacillus in the gut microbiota was observed after 32G-administration. The lactobacilli increased were determined to be commensal lactobacilli. In the second study different L. casei strains were compared. While some L. casei strains didn't modify the cecum-microbiota, others reconfigured the microbial composition in a strain-specific manner. Moreover, the results suggest there is a correlation between a strain's ability to alter the gut microbiota composition with the strain's ability to alter the expression of PRRs and AMPs. The last study employed a combination of bioinformatics, in vitro and in vivo studies to explore the mechanisms of L. casei probiotic action. L. casei strains were determined to contain a diversity of cell-surface structures. In vitro studies revealed that both cell-surface components and supernatant participate in immunomodulation. In vivo results suggest that supernatant from 32G is likely involved in altering the gut microbiota, while cell-surface components are involved in modulating the immune system.;In conclusion, L. casei alters the composition of gut microbiota and modulates the innate immune system in a strain-specific manner. These alterations were determined to be dose and time dependent. There is extensive genetic diversity in cell-surface components within L. casei strains and this diversity contributes to the strain-specific variation in immunomodulation and host-bacteria interactions observed within species. Additionally, it is clear that supernatant are also involved in probiotic function. This thesis begins the process of identifying potential mechanisms of L. casei probiotic activity. |
