Keio University Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q) held an open seminar as follows:

Poster (PDF)

Abstract

Microbiome Therapeutics for Inflammatory Disorders and Cancer
“Our immune system induces active immunity against diverse pathogens while suppressing destructive hyper-immune responses against innocuous antigens. This immune homeostasis is maintained by concerted crosstalk between genetic factors and environmental cues, including intestinal gut microbiota. Dysregulation of the commensal flora is closely linked to functional changes in the immune and neuronal systems. Subsequently, it contributes to the development of immune disorders (such as autoimmunity and allergies), neuronal disorders (depression, autism spectrum disorders), and metabolic syndromes. Moreover, altered gut microbiota affects differential responsiveness to immune checkpoint inhibitors targeting PDL1/PD-1 and CTLA4. The candidates of microbiome therapeutics include bioactive molecules derived from the microbiome (metabolites and cellular components) and the bug itself (live biotherapeutic products, LBP).
To identify anti-inflammatory and immune-stimulatory microorganisms, we have developed a platform screening system, AvatiomeTM, an innovative pre-clinical model system that mimics the human body’s immune system and microbiome. Avatiome ™ incorporates up-to-date technologies such as immunophenotyping, single-cell transcriptomics, and artificial intelligence (AI) systems to develop novel therapeutics targeting intractable neuronal, systemic inflammatory diseases and cancers. Through the screening system, we have identified immunostimulatory (IMB001) or immunoregulatory (IMB002) microorganisms and further defined the effector molecules that recapitulate the functionality of whole bacteria. I will discuss the current status of microbiome therapeutics and our work on identifying IMB002 and IMB001, which show anti-inflammatory and anti-cancer activities, respectively. Moreover, I will also discuss the underlying mechanism of action of the effector molecules in the diverse pre-clinical models and potential therapeutic applications.”

Selected papers related to the lecture

1. Cell surface polysaccharides of Bifidobacterium bifidum induce Foxp3+ regulatory T cells. Science Immunology. 2018 Oct 19;3(28). pii: eaat6975. doi: 10.1126/sciimmunol.aat6975.
2. Intestinal Microbiota Controls Acute Kidney Injury Severity by Immune Modulation. Kidney Int. 2020: S0085-2538(20)30553-6
3. Probiotics-derived metabolite ameliorates skin allergy by promoting differentiation of FOXP3+ regulatory T cells. J Allergy Clin Immunol 2021. 147 (4), 1517-1521
4.  Structural specificities of cell surface β-glucan polysaccharides determine commensal yeast-mediated immuno-modulatory activities. Nature Communications. 2021. June 14; 12(1):3611
5. A dietary commensal microbe enhances anti-tumor immunity by activating tumor macrophages to sequester iron. Nature Immunology. 2024 May;25(5):790-801