Yuya Kiguchi

All Publications

• Giant extrachromosomal element "Inocle" potentially expands the adaptive capacity of the human oral microbiome NATURE COMMUNICATIONS Kiguchi, Y., Hamamoto, N., Kashima, Y., Runtuwene, L. R., Ishizaka, A., Kuze, Y., Enokida, T., Tanaka, N., Tahara, M., Kageyama, S., Fujisawa, T., Yamashita, R., Kanai, A., Tuda, J. S. B., Mizutani, T., Suzuki, Y. 2025; 16 (1): 7397

  Abstract

  Survival strategy of bacteria is expanded by extrachromosomal elements (ECEs). However, their genetic diversity and functional roles for adaptability are largely unknown. Here, we discover a novel family of intracellular ECEs using 56 saliva samples by developing an efficient microbial DNA extraction method coupled with long-read metagenomics assembly. Even though this ECE family was not hitherto identified, our global prevalence analysis using 476 salivary metagenomic datasets elucidates that these ECEs reside in 74% of the population. These ECEs, which we named, "Inocles", are giant plasmid-like circular genomic elements of 395 kb in length, including Streptococcus as a host bacterium. Inocles encode a series of genes that contribute to intracellular stress tolerance, such as oxidative stress and DNA damage, and cell wall biosynthesis and modification involved in the interactions with oral epithelial cells. Moreover, Inocles exhibit significant positive correlations with immune cells and proteins responding to microbial infection in peripheral blood. Intriguingly, we examine and find their marked reductions among 68 patients of head and neck cancers and colorectal cancers, suggesting its potential usage for a novel biomarker of gastrointestinal cancers. Our results suggest that Inocles potentially boost the adaptive capacity of host bacteria against various stressors in the oral environment.

  View details for DOI 10.1038/s41467-025-62406-5

  View details for Web of Science ID 001548594700034

  View details for PubMedID 40790024

  View details for PubMedCentralID PMC12340149

• Tyzzerella nexilis strains enriched in mobile genetic elements are involved in progressive multiple sclerosis. Cell reports Takewaki, D., Kiguchi, Y., Masuoka, H., Manu, M. S., Raveney, B. J., Narushima, S., Kurokawa, R., Ogata, Y., Kimura, Y., Sato, N., Ozawa, Y., Yagishita, S., Araki, T., Miyake, S., Sato, W., Suda, W., Yamamura, T. 2024; 43 (10): 114785

  Abstract

  Multiple sclerosis (MS) is an autoimmune-demyelinating disease with an inflammatory pathology formed by self-reactive lymphocytes with activated glial cells. Progressive MS, characterized by resistance to medications, significantly differs from the non-progressive form in gut microbiome profiles. After confirming an increased abundance of "Tyzzerella nexilis" in various cohorts of progressive MS, we identified a distinct cluster of T. nexilis strains enriched in progressive MS based on long-read metagenomics. The distinct T. nexilis cluster is characterized by a large number of mobile genetic elements (MGEs) and a lack of defense systems against MGEs. Microbial genes for sulfate reduction and flagella formation with pathogenic implications are specific to this cluster. Moreover, these flagellar genes are encoded on MGEs. Mono-colonization with MGE-enriched T. nexilis made germ-free mice more susceptible to experimental autoimmune encephalomyelitis. These results indicate that the progression of MS may be promoted by MGE-enriched T. nexilis with potentially pathogenic properties.

  View details for DOI 10.1016/j.celrep.2024.114785

  View details for PubMedID 39341204

• Extensive gut virome variation and its associations with host and environmental factors in a population-level cohort. Nature communications Nishijima, S., Nagata, N., Kiguchi, Y., Kojima, Y., Miyoshi-Akiyama, T., Kimura, M., Ohsugi, M., Ueki, K., Oka, S., Mizokami, M., Itoi, T., Kawai, T., Uemura, N., Hattori, M. 2022; 13 (1): 5252

  Abstract

  Indigenous bacteriophage communities (virome) in the human gut have a huge impact on the structure and function of gut bacterial communities (bacteriome), but virome variation at a population scale is not fully investigated yet. Here, we analyse the gut dsDNA virome in the Japanese 4D cohort of 4198 deeply phenotyped individuals. By assembling metagenomic reads, we discover thousands of high-quality phage genomes including previously uncharacterised phage clades with different bacterial hosts than known major ones. The distribution of host bacteria is a strong determinant for the distribution of phages in the gut, and virome diversity is highly correlated with anti-viral defence mechanisms of the bacteriome, such as CRISPR-Cas and restriction-modification systems. We identify 97 various intrinsic/extrinsic factors that significantly affect the virome structure, including age, sex, lifestyle, and diet, most of which showed consistent associations with both phages and their predicted bacterial hosts. Among the metadata categories, disease and medication have the strongest effects on the virome structure. Overall, these results present a basis to understand the symbiotic communities of bacteria and their viruses in the human gut, which will facilitate the medical and industrial applications of indigenous viruses.

  View details for DOI 10.1038/s41467-022-32832-w

  View details for PubMedID 36068216

  View details for PubMedCentralID PMC9448778

• Long-read metagenomics of multiple displacement amplified DNA of low-biomass human gut phageomes by SACRA pre-processing chimeric reads. DNA research : an international journal for rapid publication of reports on genes and genomes Kiguchi, Y., Nishijima, S., Kumar, N., Hattori, M., Suda, W. 2021; 28 (6)

  Abstract

  The human gut bacteriophage community (phageome) plays an important role in the host's health and disease; however, the entire structure is poorly understood, partly owing to the generation of many incomplete genomes in conventional short-read metagenomics. Here, we show long-read metagenomics of amplified DNA of low-biomass phageomes with multiple displacement amplification (MDA), involving the development of a novel bioinformatics tool, split amplified chimeric read algorithm (SACRA), that efficiently pre-processed numerous chimeric reads generated through MDA. Using five samples, SACRA markedly reduced the average chimera ratio from 72% to 1.5% in PacBio reads with an average length of 1.8 kb. De novo assembly of chimera-less PacBio long reads reconstructed contigs of ≥5 kb with an average proportion of 27%, which was 1% in contigs from MiSeq short reads, thereby dramatically improving contig length and genome completeness. Comparison of PacBio and MiSeq contigs found MiSeq contig fragmentations frequently near local repeats and hypervariable regions in the phage genomes, and those caused by multiple homologous phage genomes coexisting in the community. We also developed a reference-independent method to assess the completeness of the linear phage genomes. Overall, we established a SACRA-coupled long-read metagenomics robust to highly diverse gut phageomes, identifying high-quality circular and linear phage genomes with adequate sequence quantity.

  View details for DOI 10.1093/dnares/dsab019

  View details for PubMedID 34586399

  View details for PubMedCentralID PMC8513251

• Ectopic colonization of oral bacteria in the intestine drives T_H1 cell induction and inflammation SCIENCE Atarashi, K., Suda, W., Luo, C., Kawaguchi, T., Motoo, I., Narushima, S., Kiguchi, Y., Yasuma, K., Watanabe, E., Tanoue, T., Thaiss, C. A., Sato, M., Toyooka, K., Said, H. S., Yamagami, H., Rice, S. A., Gevers, D., Johnson, R. C., Segre, J. A., Chen, K., Kolls, J. K., Elinav, E., Morita, H., Xavier, R. J., Hattori, M., Honda, K. 2017; 358 (6361): 359-+

  Abstract

  Intestinal colonization by bacteria of oral origin has been correlated with several negative health outcomes, including inflammatory bowel disease. However, a causal role of oral bacteria ectopically colonizing the intestine remains unclear. Using gnotobiotic techniques, we show that strains of Klebsiella spp. isolated from the salivary microbiota are strong inducers of T helper 1 (TH1) cells when they colonize in the gut. These Klebsiella strains are resistant to multiple antibiotics, tend to colonize when the intestinal microbiota is dysbiotic, and elicit a severe gut inflammation in the context of a genetically susceptible host. Our findings suggest that the oral cavity may serve as a reservoir for potential intestinal pathobionts that can exacerbate intestinal disease.

  View details for DOI 10.1126/science.aan4526

  View details for Web of Science ID 000413251000041

  View details for PubMedID 29051379

  View details for PubMedCentralID PMC5682622