마이크로바이옴 타겟 치료제 현황과 전망 Current Status and Future Prospective of Microbiome Therapeutics

Intestinal microbiota plays a critical role in the modulation of human health. Dysregulation of the commensal flora is closely linked to functional changes of the immune system and subsequently contributes to development of immune disorders. Probiotics are considered prophylactic or therapeutic modalities to restore homeostasis of host immune system. However, efficacy of probiotics is strain specific and shows great variation even within the same species. Moreover, European Food Safety Authority (EFSA) and other regulatory agencies request to identify the effector molecules and mode of action of probiotics related with functional claims. Recent studies also suggest that taking inappropriate strains of probiotic strains could exacerbate ongoing immune disorders when patients or experimental animals are on the process of disease development. Thereby providing tailored probiotic strain(s) is essential to the people who are in the sage of disease development. How to identify and characterize the immune modulatory properties of specific probiotic strains? What are the effector molecules and mode of action of them? How to prove their potential efficacy? To answer these questions, we have developed and identified different types of probiotic strains that could either induce regulatory T cells (Treg) or suppressing Treg cell activity while activating cytotoxic activity of CD8 T cells. As an example, we have selected Bifidobacterium bifidum PRI1 (Bb PRI1) as a Treg-inducing bacteria based on its IL-10highIL-12low inducing capabilities. Mono-association of Bb PRI1significantly enhanced the generation of induced CD4+Foxp3+ Helioslow Treg (iTreg) cells from the naive CD4+ T cell populations mainly in the lamina propria of the colon. Mechanistically, we identified Bb PRI1-derived capsular polysaccharide (CPS) as the key component that in a TLR2 dependent manner is capable of inducing regulatory DCs, which in turn enhanced iTreg cells generation. These findings provide new insights into the molecular mechanisms by which Treg-inducing probiotics-host interaction could establish immunological homeostasis in the gut. Our studies also provide a proof of concept how specific probiotic strain could modulate host’s immune system.2