Immunomodulatory properties of probiotic bacteria

Probiotics are living microorganisms, which when administered in adequate amounts confer a health benefit on the host. They have been reported to relieve acute diarrhoea, atopic dermatitis and irritable bowel syndrome in disease-specific animal studies and in human intervention trials. However, probiotics are regularly consumed by general healthy population with limited knowledge in the immunomodulation of probiotics of local and systemic immune responses in healthy experimental models. Serving as the first line of defense against microbial infections and the largest immunological organ in animal host, the epithelium lining the small and large intestine is supposed to be the first organ to encounter probiotics as probiotics are always orally taken. It is believed that probiotics regulate the local immunities in the gut, which acts as the pivot in modulating the systemic immune responses. Accordingly, it was hypothesized that probiotic bacteria can modulate both local and systemic immune responses in healthy population; and the immunomodulation of combination of probiotics is different from that of individual strains. Wildtype healthy C57BL/6 mice were fed with different probiotic strains − Lactobacillus rhamnosus GG (LGG), Lactobacillus rhamnosus LC705 (LC705), Bifidobacterium breve Bb99 (Bb99), Propionibacterium freudenreichii ssp. shermanii JS (PJS) or Escherichia coli Nissle 1917 (EcN), or mixture of probiotics − GGmix (LGG, LC705, Bb99 and PJS) and ECPJSmix (PJS and EcN), for three weeks. After that, intestine, liver, spleen and blood were investigated. Probiotics suppressed intestinal T helper (Th)17 immune response but enhanced systemic (hepatic and splenic) Th17 immune response, suggesting that immune homeostasis was maintained in healthy individuals. Mechanism of action of LGG was further studied in this project as LGG is the widely studied probiotics. It was hypothesized that LGG exerts immunomodulatory effects by bacteria cells and/or its derived soluble factors such as lactic acid. Immunomodulatory effects of LGG cells and their soluble factors on dendritic cells (DCs), macrophages and monocytes from healthy blood donors were investigated as antigen-presenting cells (APCs) are pivots of bridging innate and adaptive immunities. Cytokine secretion profile, expressions of toll-like receptors (TLRs) and activation-related receptors of the APCs were examined. Both LGG cells and their soluble factors promoted type 1-responsiveness while soluble factors promoted type 17-responsiveness as well. Yet, lactic acid seemed not to be the one which enhanced type 1 and type 17 immune responses in soluble factors. With better understanding on the immunomodulation of probiotics in healthy models, prophylactic efficacy of probiotics in preventing infections and diseases can be availed.published_or_final_versionBiological SciencesDoctoralDoctor of Philosoph