Regulatory properties of lactic acid bacteria for improving immune homeostasis

Lactic acid bacteria (LAB) are a group of lactic acid-producing bacteria and LAB supplementation has been associated with diverse health-promoting effects. However, the mechanisms involved remain ambiguous. Considering the high numbers of LAB strains that might qualify for dietary or pharmaceutical bacterial formulations, high-throughput screening systems for identifying potential beneficial strains are required.In this thesis immunomodulatory properties of different LAB strains and species were studied. We observed species- and strain-dependent immune effects of LABs, which were largely dictated by the interactions between LAB-related ligands and signalling receptors on the host cells, specifically Toll-like receptors (TLRs). LAB-related ligands were found to be either on bacterial cells or released into bacterial culture supernatants. Moreover, LAB ligands in the culture supernatants might possess different immune-signalling properties from ligands on bacterial cells. We showed that LAB strains might prevent epithelial barrier integrity loss via acting on specific signalling pathways, i.e. TLR2 and protein kinase C. Mucus barrier-regulatory capacities of LABs were also evaluated. The expression of mucus-associated goblet cell products were modulated by LABs in a species- and strain-dependent manner. LAB-secreted products also conferred regulations on mucus-related genes. Subepithelial fibroblasts were proved to contribute to mucus regulation, and should be used to establish in vitro cell models for assessing mucus-regulating potentials of LABs. Our findings suggest that both bacterial strains and their secreted components should be considered when designing functional foods. We provide technology platforms for selections of candidate strains or bacterial secreted factors with potential immune-active or gut barrier-modulating functions