An Integrated Multi-Omic Single-Cell Based Atlas to Translate Parabacteroides Goldsteinii Ameliorative Effect and Mechanism for Copd and Lung Cancer Immuno-/Metabolic- Therapy( I )

  • Lai, Hsin-Chih (PI)
  • Lin, Jun Hong (CoPI)
  • Lu, Chia Chen (CoPI)
  • Wu, Yu Wei (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by long term sustained chronic inflammation manifested as accumulation of inflammatory cells, proteases and proinflammatory cytokines, leading to lung tissue destruction. In our recent studies, by using a mouse cigarette smoking (CS) model and faecal microbiota transplantation approach combined with antibiotics treatment, we established the gut microbiota-lung COPD axis. We subsequently identified a commensal bacterial species Parabacteroides goldsteinii that presented most significant negative association with COPD development. We then isolated this bacterium named P. goldsteinii MTS01 (Pg MTS01) and found that oral administration of Pg MTS01 on its own significantly ameliorates the CS-induced COPD syndromes. Recently, Pg MTS01-derived lipopolysaccharide (LPS) which antagonizes E. coli LPS induced inflammations in vitro was further shown to be the functional component. Our preliminary studies further strongly speculated Pg MTS01-derived capsular polysaccharides (CPS) and extracellular vesicles (EV) might also be functional components. Meanwhile, Pg MTS01 also significantly ameliorates the survival time and tumor size in lung cancer mice model. Therefore, this joint research proposal with integration of microbiology, immunity, biochemistry, and bioinformatic platforms will be subdivided into six aims: (1) Evaluation of the effect of Pg MTS01-derived functional components in amelioration of COPD, (2) Elucidation of the structure and functional moiety of the functional components, (3) Unraveling the mechanisms of Pg MTS01-derived functional components by using integrated multi-omics studies, (4) Exploration of the detailed ameliorative mechanisms of Pg MTS01 functional components on target cells such as B cells, Dendritic cells and T cells in vitro, (5) Development of next-generation probiotics, functional components, and their induced immune cells as well as metabolites to treat COPD, (6) Examination of the effects of Pg MTS01-derived functional components combined with PD-L1 related immunotherapy for amelioration of lung cancer. This project will shed light on the mechanisms of Pg MTS01-derived functional components in ameliorating COPD and lung cancer. More importantly, immuno- and metabolic- therapy based approaches to ameliorate COPD and lung cancer by next-generation probiotic P. goldsteinii will be developed.

Project IDs

Project ID:PB10906-0054
External Project ID:MOST109-2327-B182-001
StatusFinished
Effective start/end date01/05/2030/04/21

Keywords

  • Parabacteroides goldsteinii
  • COPD
  • lung cancer
  • metabolite
  • functional components

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