Biomedical subjects

Eiko Hayase

Publications and source records attributed to Eiko Hayase.

5 recordsLinked to original sources

PubMed2026

First-line fecal microbiota transplantation for the management of immune checkpoint inhibitor-mediated diarrhea and colitis.

Immune checkpoint inhibitor (ICI) therapy commonly leads to adverse events such as ICI-mediated diarrhea and colitis (IMDC). Fecal microbiota transplantation (FMT) remains an option for patients with refractory colitis. We report a multi-omics profiling of patients receiving first-line FMT for IMDC. In our preliminary analysis, 10 (76.9%) patients achieve clinical response, with a median time to clinical improvement of 1.5 (1-10.5) days. Among responder patients with baseline and follow-up samples, 6 (75%) show an increase in alpha-diversity post-FMT. Pre-FMT samples show an increase in the abundance scores of plasma cells, neutrophils, macrophages (M1 and M2), memory activated and resting memory CD4+ T cells, CD8+ T cells, T follicular helper (Tfh) cells, and regulatory T cells (Tregs), all of which decrease post-FMT. In a small cohort of patients, we identify potential mechanisms for FMT response and demonstrate that first-line FMT in patients with IMDC (NCT04038619) can be effective.

FMT↗

PubMed2026

Inclusion of Multi-Omic Biomarkers Improves Prediction Accuracy of Response, Relapse, and Overall Survival in Acute Myeloid Leukemia Patients Receiving High-Intensity Induction Chemotherapy.

BACKGROUND: Despite advancements in genetic markers for acute myeloid leukemia (AML) risk stratification, outcome prediction remains challenging due to disease heterogeneity and dynamic genetic changes, highlighting the need for reliable biomarkers to improve AML treatment strategies and patient outcomes. To refine outcome predictions, we investigated the use of microbial-derived biomarkers to predict composite complete remission (CRc), relapse, and survival for patients on high- and low-intensity regimens, and to integrate those variables into the widely clinically utilized European Leukemia Network (ELN-2022) genetic risk classification model for high-intensity-treated patients. METHODS: We first developed machine learning models that integrate baseline fecal metabolomics, 16S rRNA-based stool microbiome features, and clinical metadata (sex, antibiotic administration, AML somatic mutations, and cytogenetics) from two cohorts of AML patients (n = 83) undergoing remission induction chemotherapy. Univariate tests and sparse canonical correlation analysis were employed for variable selection and to explore fecal metabolite-microbe relationships. A robust machine learning approach using XGBoost was employed, with 100 stratified data splits (80% training, 20% testing) and coarse-to-fine hyperparameter optimization. Variable importance was aggregated across all models to select key predictors. RESULTS: For high-intensity-treated patients, XGBoost models achieved aggregated AUROC scores of 0.719, 0.729, and 0.65 for CRc, relapse, and overall survival, respectively. For low-intensity-treated patients, these models achieved aggregate AUROC scores of 0.945, 0.724, and 0.768 for these same outcomes, respectively. Integrating the biomarkers identified in the high-intensity machine-learning models with the current ELN-2022 AML risk stratification system effectively stratified patients into risk categories, which obtained higher concordance indices and likelihood ratios, demonstrating improved prognostic accuracy for each outcome compared to ELN-2022 alone. CONCLUSIONS: The inclusion of microbial-derived biomarkers serves as a robust prognostic tool to improve outcome prediction in AML patients, highlighting the potential of its integration into AML risk assessment and paving the way for personalized treatment strategies and improved patient outcomes.

Humans↗

PubMed2025

Microbial signals in primary and metastatic brain tumors.

Gliomas and brain metastases are associated with poor prognosis, necessitating a deeper understanding of brain tumor biology and the development of effective therapeutic strategies. Although our group and others have demonstrated microbial presence in various tumors, recent controversies regarding cancer-type-specific intratumoral microbiota emphasize the importance of rigorous, orthogonal validation. This prospective, multi-institutional study included a total of 243 samples from 221 patients, comprising 168 glioma and brain metastases samples and 75 non-cancerous or tumor-adjacent tissues. Using stringent fluorescence in situ hybridization, immunohistochemistry and high-resolution spatial imaging, we detected intracellular bacterial 16S rRNA and lipopolysaccharides in both glioma and brain metastases samples, localized to tumor, immune and stromal cells. Custom 16S and metagenomic sequencing workflows identified taxa associated with intratumoral bacterial signals in the tumor microenvironment; however, standard culture methods did not yield readily cultivable microbiota. Spatial analyses revealed significant correlations between bacterial 16S signals and antimicrobial and immunometabolic signatures at regional, neighborhood and cellular levels. Furthermore, intratumoral 16S bacterial signals showed sequence overlap with matched oral and gut microbiota, suggesting a possible connection with distant communities. Together, these findings introduce microbial elements as a component of the brain tumor microenvironment and lay the foundation for future mechanistic and translational studies.

Humans↗

PubMed2024

Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.

Graft vs Host Disease↗

PubMed2023

Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease.

Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality.

Bacteroides ovatus↗