RIKEN IMS AnnualReport 2020
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The Laboratory for Microbiome Sciences has been engaged in the study of 47complex interactions between symbiotic microbial ecosystems (composed of bacteria, viruses, and fungi) and their hosts. Through the development of new experimental and informatics-based technologies using state-of-the-art se-quencers, we aim to comprehensively understand and eventually control these symbiotic microbial ecosystems by clarifying not only the microbiome struc-ture variation among individuals but also the time-series dynamics.Our team has published 19 papers in FY2020. In one representative paper, we revealed for the first time the ecological and functional differences in the gut microbiome between patients with relapsing-remitting multiple sclero-sis (RRMS) and secondary progressive multiple sclerosis (SPMS) (PNAS, 117:22402-22412, 2020). Whole metagenomic analysis of RRMS and SPMS samples revealed that the gut microbiome of SPMS patients has an enhance-ment in oxidative stress and microbial DNA repair, which suggests a possible association between gut-derived oxidative stress and chronic neuroinflamma-tion (Figure). These breakthrough results could lead to the development of in-novative treatments for progressive MS.Currently we are working on a longitudinal metagenomic analysis of the mouse gut microbiome from birth to death. Despite a shared genetic back-ground, we observed diverse phenotypes of hosts and related transitions of the gut microbiomes. We also found a strong association between lifespan and tem-poral dynamics of the abundance of several microbes. Most of these microbes were “life-core” microbes that are observed at most periods throughout the life of the mouse. This study implies the possibility of a deep association between lifespan and the temporal dynamics of the abundance of “life-core” microbes. Understanding the relationship between microbial dynamics and the host could lead to future control of human health based on gut microbiome time-course monitoring.Figure: Microbial function based on metage-nomic data (comparison between relapsing-remitting MS patients and secondary progres-sive MS patients)(A) 38 genes were increased and 14 were decreased in patients with secondary progressive MS when compared with healthy subjects. (B) We ranked the metabolic pathways including these genes in descending order of the degree of increase or decrease between the two groups. (C, D) Among the genes included in the mis-match repair pathway, the relative abundances of two genes, DNA adenine methylase and DNA polymerase III delta subunit, were increased in secondary progressive MS patients when compared to relapsing-remitting MS patients. HS, Healthy Subjects; RRMS, relapsing-remitting MS; SPMS, secondary progressive MS; NMOSD, Neuromyelitis Optica Spectrum Disorder. *p <0.05 (Wilcoxon rank sum test). PNAS, 117:22402-22412, (Takewaki D, Suda W† et al. Proc Natl Acad Sci U S A. 117, 22402-22412 (2020) †Corresponding author)Recent Major PublicationsTakewaki D, Suda W†, Sato W, Takayasu L, Kumar N, Kimura K, Kaga N, Mizuno T, Miyake S, Hattori M, Yama-mura T†. Alterations of the gut ecological and functional microenvironment in different stages of multiple sclero-sis. Proc Natl Acad Sci U S A 117, 22402-22412 (2020)Masuoka H, Suda W†, Tomitsuka E, Shindo C, Takayasu L, Horwood P, Greenhill AR, Hattori M, Umezaki M, Hirayama K. The influences of low protein diet on the intestinal microbiota of mice. Sci Rep 10, 17077 (2020)Miyauchi E, Kim SW, Suda W, Kawasumi M, Onawa S, Taguchi-Atarashi N, Morita H, Taylor TD, Hattori M, Ohno H†. Gut microorganisms act together to exacerbate inflammation in spinal cords. Nature 585, 102-106 (2020)Invited presentationsSuda W. “Recent advance in human gut microbiome study” International Workshop on Eukaryotic Microbi-ome (Tokyo, Japan) March 2020Laboratory for Microbiome SciencesTeam Leader: Hiroshi Ohno

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