The gut microbiota is reported to be related to obesity, and visceral fat is reported to be strongly associated with cardiovascular disease and overall mortality. However, the association between the gut microbiota and obesity has mainly been studied using body mass index (BMI) as a proxy for obesity. We investigated the relationship of both visceral fat and BMI with the gut microbiota stratified by sex in a population-based cross-sectional study of Japanese men and women 20–76 years of age (n = 1001). Women with a higher visceral fat area (VFA) harboured a higher relative abundance of the Firmicutes phylum (P for trend <0.001) and a lower relative abundance of the Bacteroidetes phylum (P for trend 0.030), whereas men with higher VFA harboured a lower relative abundance of the Firmicutes phylum (P for trend 0.076) and a higher relative abundance of the Bacteroidetes phylum (P for trend 0.013). Similar results were obtained using BMI as an index, but the differences were not significant in men. At the genus level, Blautia was the only gut microbe significantly and inversely associated with VFA regardless of sex. In conclusion, at the genus level we found that Blautia was the only gut microbe significantly and inversely associated with VFA, regardless of sex.

STAG2 encodes a cohesin component and is frequently mutated in myeloid neoplasms, showing highly significant co-mutation patterns with other drivers, including RUNX1. However, the molecular basis of cohesin-mutated leukemogenesis remains poorly understood. Here we show a critical role of an interplay between Stag2 and Runx1 in the regulation of enhancer-promoter looping and transcription in hematopoiesis. Combined loss of Stag2 and Runx1, which co-localize at enhancer-rich, Ctcf-deficient sites, synergistically attenuates enhancer-promoter loops, particularly at sites enriched for RNA polymerase II and Mediator, and deregulates gene expression, leading to myeloid-skewed expansion of hematopoietic stem/progenitor cells (HSPCs) and myelodysplastic syndromes (MDS). Attenuated enhancer-promoter loops in Stag2/Runx1-deficient cells are associated with downregulation of genes with high basal transcriptional pausing, which are important for regulation of HSPCs. Down-regulation of high-pausing genes is also confirmed in STAG2/cohesin-mutated primary leukemia samples. Our results highlight a unique STAG2/RUNX1 interplay in gene regulation and provide insights into cohesin-mutated leukemogenesis. SignificanceWe demonstrate a critical role of an interplay between Stag2 and a master transcription factor of hematopoiesis, Runx1, in MDS development, and further reveal their contribution to regulation of high-order chromatin structures, particularly enhancer-promoter looping, and the link between transcriptional pausing and selective gene dysregulation caused by cohesin deficiency.

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DNA sequences are translated into protein coding sequences and then further assigned to protein families in metagenomic analyses, because of the need for sensitivity. However, huge amounts of sequence data create the problem that even general homology search analyses using BLASTX become difficult in terms of computational cost. We designed a new homology search algorithm that finds seed sequences based on the suffix arrays of a query and a database, and have implemented it as GHOSTX. GHOSTX achieved approximately 131–165 times acceleration over a BLASTX search at similar levels of sensitivity. GHOSTX is distributed under the BSD 2-clause license and is available for download at http://www.bi.cs.titech.ac.jp/ghostx/. Currently, sequencing technology continues to improve, and sequencers are increasingly producing larger and larger quantities of data. This explosion of sequence data makes computational analysis with contemporary tools more difficult. We offer this tool as a potential solution to this problem.

Cigarette smoking affects the oral microbiome, which is related to various systemic diseases. While studies that investigated the relationship between smoking and the oral microbiome by 16S rRNA amplicon sequencing have been performed, investigations involving metagenomic sequences are rare. We investigated the bacterial species composition in the tongue microbiome, as well as single-nucleotide variant (SNV) profiles and gene content of these species, in never and current smokers by utilizing metagenomic sequences. Among 234 never smokers and 52 current smokers, beta diversity, as assessed by weighted UniFrac measure, differed between never and current smokers (pseudo-F = 8.44, R 2 = 0.028, p = 0.001). Among the 26 species that had sufficient coverage, the SNV profiles of Actinomyces graevenitzii, Megasphaera micronuciformis, Rothia mucilaginosa, Veillonella dispar, and one Veillonella sp. were significantly different between never and current smokers. Analysis of gene and pathway content revealed that genes related to the lipopolysaccharide biosynthesis pathway in Veillonella dispar were present more frequently in current smokers. We found that species-level tongue microbiome differed between never and current smokers, and 5 species from never and current smokers likely harbor different strains, as suggested by the difference in SNV frequency.