Publications by authors named "Isobe J"

Unlabelled: The concept of genome-microbiome interactions, in which the microenvironment determined by host genetic polymorphisms regulates the local microbiota, is important in the pathogenesis of human disease. In otolaryngology, the resident bacterial microbiota is reportedly altered in non-infectious ear diseases, such as otitis media pearls and exudative otitis media. We hypothesized that a single-nucleotide polymorphism in the ATP-binding cassette sub-family C member 11 () gene, which determines earwax properties, regulates the ear canal microbiota.

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Yersinia pseudotuberculosis (Ypt) is a gram-negative bacterium that infects both humans and animals primarily through fecal‒oral transmission. While Ypt causes acute gastroenteritis in humans, an association with Kawasaki disease (KD), a disease that primarily affects infants and young children and causes multisystemic vasculitis, has also been suspected. Although KD represents a significant health concern worldwide, the highest annual incidence rate is reported in Japan.

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Gut bacteria play pivotal roles in the antitumor effects of immune checkpoint inhibitors (ICIs). However, antimicrobial therapy, often necessary for infections in cancer patients, can reduce the efficacy of ICIs. The potential of probiotics to restore ICI efficacy remains uncertain.

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Paratyphoid B fever (PTB) is caused by an invasive lineage (phylogroup 1, PG1) of Salmonella enterica serotype Paratyphi B (SPB). However, little was known about the global population structure, geographic distribution, and evolution of this pathogen. Here, we report a whole-genome analysis of 568 historical and contemporary SPB PG1 isolates, obtained globally, between 1898 and 2021.

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  • Natural killer group 2 member D ligands (NKG2DLs) in cancer cells can either activate immune responses or help tumors evade them, depending on their levels in the cells.
  • In pancreatic cancer cells (PANC-1), soluble MICB (sMICB) is found in the culture supernatant, which may saturate NKG2D T cells and inhibit their activation by membrane-bound MICB (mMICB).
  • Inhibiting the enzyme ADAM17, which contributes to the shedding of MICB, can help maintain mMICB expression and enhance NKG2D T cell activation, demonstrating a potential strategy to improve anti-tumor immune responses.
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  • Ninety-five participants, including residents (average age 88) and staff (average age 51), demonstrated strong antibody responses after multiple doses of mRNA vaccines.
  • The findings support continued mRNA booster vaccinations for older adults in high-risk settings, as they generate robust immunity with minimal adverse effects.
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  • * In Toyama, 2023, strains of C. perfringens were studied from patients and curry food linked to an outbreak, revealing the cpe gene in both.
  • * SNP analysis indicated that patient and curry food isolates likely originated from the same source, while employee samples were not related, highlighting SNP analysis as a promising method for tracking C. perfringens outbreaks.
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  • Shiga toxin-producing E. coli (STEC) causes severe gastrointestinal issues, particularly linked to Stx2, which poses greater risks than Stx1.
  • A study of 71 strains in the O145:H28 lineage reveals the dynamic nature of Stx phages, including their acquisition, transfer, and variations affecting Stx2 production levels.
  • Short-tailed Stx2 phages are associated with higher production levels of Stx2 than long-tailed variants, highlighting genetic differences that influence these levels.
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The low response rate of immune checkpoint inhibitors (ICIs) is a challenge. The efficacy of ICIs is influenced by the tumour microenvironment, which is controlled by the gut microbiota. In particular, intestinal bacteria and their metabolites, such as short chain fatty acids (SCFAs), are important regulators of cancer immunity; however, our knowledge on the effects of individual SCFAs remains limited.

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  • The study investigates the decline of streptococcal toxic shock syndrome (STSS) cases in Japan, particularly its connection to group A Streptococcus (GAS) strains, and aims to understand the reasons behind this decrease.
  • Researchers analyzed 526 GAS isolates from STSS patients between 2019 and 2022, noting a significant decrease in the prevalence of emm1 strains after the COVID-19 pandemic began.
  • The findings suggest that changes in public health measures during the pandemic, such as mask-wearing, may have reduced infections, particularly those from strains linked to pharyngeal infections, contributing to the reduction in STSS cases.
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  • Public bath facilities in Japan are linked to infection outbreaks, prompting a study on the bacterial communities in their water using 16S rRNA gene amplicon sequencing.
  • The research found distinct differences in bacterial community structure between bath and shower water, with factors like chlorine levels and pH influencing these communities.
  • Additionally, common bacterial species were identified, highlighting the complexity of interactions among bacteria and the need for better hygiene management to prevent infections.
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  • Researchers explored the relationship between intestinal bacteria and postoperative recurrence in esophageal cancer patients after preoperative chemotherapy.
  • They used 16S rRNA metagenome sequencing and machine learning analysis to identify specific bacteria linked to cancer recurrence.
  • The study highlighted Butyricimonas and Actinomyces as potentially significant biomarkers, with Butyricimonas suggested as a factor in postoperative recurrence, warranting further investigation into their immune regulation roles.
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  • Immune checkpoint inhibitors, like PD-1 inhibitors, have changed cancer treatment, but only 10%-30% of patients with solid tumors respond well to these therapies.
  • This study investigated how the occupancy of the PD-1 receptor in different T-cell populations, particularly effector regulatory T cells (eTregs), relates to patient outcomes and adverse effects in people treated with the drug nivolumab.
  • Findings showed that lower PD-1 occupancy on eTregs was linked to better clinical outcomes and lower mortality, suggesting that managing PD-1 signaling in these cells could enhance the effectiveness of cancer therapies.
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Hemolytic uremic syndrome (HUS) is a life-threatening disease caused by Shiga toxin-producing (STEC) infection. The treatment approaches for STEC-mediated typical HUS and atypical HUS differ, underscoring the importance of rapid and accurate diagnosis. However, specific detection methods for STECs other than major serogroups, such as O157, O26, and O111, are limited.

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Introduction: Immune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race.

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  • The study focuses on Shiga toxin-producing E. coli (STEC), particularly on the O165:H25 strain and its relationship to closely related strains, defining them all as clonal complex 119 (CC119).
  • Researchers conducted whole-genome sequencing of 202 strains to analyze their genetic similarities and differences, focusing on the presence and behavior of specific phages and virulence genes.
  • The findings revealed that the CC119 lineage retains certain genetic traits that enhance virulence, but also shows notable variations in toxin production and lacks genes typical for tellurite resistance, indicating potential vulnerabilities in these strains.
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  • The study focused on the effectiveness of COVID-19 mRNA vaccines in nursing home residents and staff to evaluate their immune response against various SARS-CoV-2 variants, especially the Omicron subvariants.
  • Among 335 participants, including seniors with a median age of 88, researchers observed a significant increase in immune markers two months after the third vaccine dose, though these markers declined after five months.
  • Breakthrough infections were reported during the BA.5 variant wave, and older participants experienced a notable decrease in their immune response, highlighting the need for further research on the longevity of vaccine-induced immunity in older populations.
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The incidence of streptococcal toxic shock syndrome (STSS) due to group B Streptococcus (GBS) has been increasing annually in Japan and is becoming a serious challenge. Furthermore, in recent years, penicillin- or clindamycin-resistant strains used in treating streptococcal toxic shock syndrome have been reported. However, no report analyzed >100 isolates of group B Streptococcus causing streptococcal toxic shock syndrome.

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Campylobacter jejuni is a major causative agent of food poisoning, and increasing antimicrobial resistance is a concern. This study investigated 116 clinical isolates of C. jejuni from Toyama, Japan, which were isolated from 2015 to 2019.

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  • Lactose utilization in Escherichia coli is generally detected on lactose-containing media, but some Shiga toxin-producing strains (O121:H19) exhibit a delayed lactose utilization (DLU) phenotype, requiring 48 hours for detection instead of the usual 24 hours.
  • The DLU phenotype is linked to an insertion sequence (IS) disrupting the lactose utilization gene, and its effects can only be observed after exposure to lactose.
  • Research revealed that the IS can be excised, allowing the reactivation of the lactose utilization gene, and showed that most circulating O121:H19 strains harbor this IS insertion, explaining the prevalence of the DLU phenotype.
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Background: Streptococcus dysgalactiae subspecies equisimilis (SDSE) has emerged as an important cause of severe invasive infections including streptococcal toxic shock syndrome (STSS). The present study aimed to identify genes involved in differences in invasiveness between STSS and non-invasive SDSE isolates.

Methods: STSS and non-invasive SDSE isolates were analysed to identify csrS/csrR mutations, followed by a comparative analysis of genomic sequences to identify mutations in other genes.

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  • Shiga toxin (Stx)-producing Escherichia coli (STEC), particularly O121:H19, are emerging foodborne pathogens linked to serious illnesses like hemorrhagic colitis and hemolytic uremic syndrome.
  • A global whole genome sequencing analysis of 638 O121:H19 strains revealed four distinct lineages, with significant differences in their virulence factors and prophage characteristics between the major lineages L1 and L3.
  • The study highlights that strains in lineage L1 produce much higher levels of Stx2a toxin due to their highly conserved short-tailed phage genomes, while lineage L3 shows notable genetic diversity with long-tailed phages.
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Background: Legionellosis is caused by the inhalation of aerosolized water contaminated with Legionella bacteria. In this study, we investigated the prevalence of Legionella species in aerosols collected from outdoor sites near asphalt roads, bathrooms in public bath facilities, and other indoor sites, such as buildings and private homes, using amoebic co-culture, quantitative PCR, and 16S rRNA gene amplicon sequencing.

Results: Legionella species were not detected by amoebic co-culture.

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Background: Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder with a high prevalence, especially in industrialized countries. Dysbiosis of the intestinal microbiota has been observed in RA patients. For instance, new-onset untreated RA (NORA) is associated with the underrepresentation of the Clostridium cluster XIVa, including Lachnospiraceae, which are major butyrate producers, although the pathological relevance has remained obscure.

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To study the size-resolved characteristics of airborne bacterial community composition, diversity, and abundance, outdoor aerosol samples were analysed by 16S rRNA gene-targeted quantitative PCR and amplicon sequencing with Illumina MiSeq. The samples were collected using size-resolved samplers between August and October 2016, at a suburban site in Toyama City and an urban site in Yokohama City, Japan. The bacterial communities were found to be dominated by Actinobacteria, Firmicutes, and Proteobacteria.

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