Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population

Interaction between the gut microbiome and host plays a key role in human health. Here, we perform a metagenome shotgun-sequencing-based analysis of Japanese participants to reveal associations between the gut microbiome, host genetics, and plasma metabolome. A genome-wide association study (GWAS) for microbial species (n = 524) identifies associations between the PDE1C gene locus and Bacteroides intestinalis and between TGIF2 and TGIF2-RAB5IF gene loci and Bacteroides acidifiaciens. In a microbial gene ortholog GWAS, agaE and agaS, which are related to the metabolism of carbohydrates forming the blood group A antigen, are associated with blood group A in a manner depending on the secretor status determined by the East Asian-specific FUT2 variant. A microbiome-metabolome association analysis (n = 261) identifies associations between bile acids and microbial features such as bile acid metabolism gene orthologs including bai and 7β-hydroxysteroid dehydrogenase. Our publicly available data will be a useful resource for understanding gut microbiome-host interactions in an underrepresented population.Tomofuji Yoshihiko, Kishikawa Toshihiro, Sonehara Kyuto, et al. Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population. Cell Reports 42, 113324 (2023); https://doi.org/10.1016/j.celrep.2023.113324

Identification of serum metabolome signatures associated with retinal and renal complications of type 2 diabetes

Tomofuji et al. perform non-targeted metabolomics on serum samples from people with type 2 diabetes with or without complications. The authors identify metabolites associated with retinal and renal complications

ETS1 governs pathological tissue-remodeling programs in disease-associated fibroblasts

© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.Fibroblasts, the most abundant structural cells, exert homeostatic functions but also drive disease pathogenesis. Single-cell technologies have illuminated the shared characteristics of pathogenic fibroblasts in multiple diseases including autoimmune arthritis, cancer and inflammatory colitis. However, the molecular mechanisms underlying the disease-associated fibroblast phenotypes remain largely unclear. Here, we identify ETS1 as the key transcription factor governing the pathological tissue-remodeling programs in fibroblasts. In arthritis, ETS1 drives polarization toward tissue-destructive fibroblasts by orchestrating hitherto undescribed regulatory elements of the osteoclast differentiation factor receptor activator of nuclear factor-κB ligand (RANKL) as well as matrix metalloproteinases. Fibroblast-specific ETS1 deletion resulted in ameliorated bone and cartilage damage under arthritic conditions without affecting the inflammation level. Cross-tissue fibroblast single-cell data analyses and genetic loss-of-function experiments lent support to the notion that ETS1 defines the perturbation-specific fibroblasts shared among various disease settings. These findings provide a mechanistic basis for pathogenic fibroblast polarization and have important therapeutic implications.11Nsciescopu

Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population

Summary: Interaction between the gut microbiome and host plays a key role in human health. Here, we perform a metagenome shotgun-sequencing-based analysis of Japanese participants to reveal associations between the gut microbiome, host genetics, and plasma metabolome. A genome-wide association study (GWAS) for microbial species (n = 524) identifies associations between the PDE1C gene locus and Bacteroides intestinalis and between TGIF2 and TGIF2-RAB5IF gene loci and Bacteroides acidifiaciens. In a microbial gene ortholog GWAS, agaE and agaS, which are related to the metabolism of carbohydrates forming the blood group A antigen, are associated with blood group A in a manner depending on the secretor status determined by the East Asian-specific FUT2 variant. A microbiome-metabolome association analysis (n = 261) identifies associations between bile acids and microbial features such as bile acid metabolism gene orthologs including bai and 7β-hydroxysteroid dehydrogenase. Our publicly available data will be a useful resource for understanding gut microbiome-host interactions in an underrepresented population