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Biomedical subjects

Hansoo Park

Publications and source records attributed to Hansoo Park.

3 recordsLinked to original sources

Linking visceral fat accumulation to gut microbiota: key bacterial taxa and their roles in the glycogen synthesis pathway.

Obesity, marked by visceral fat accumulation, has a complex relationship with the gut microbiome that impacts body weight and fat accumulation. However, previous studies did not account for fat distribution, reflecting only overall fat mass, leaving specifics of this relationship partially understood. Here we analyzed the mechanistic links between visceral fat and the microbiome in a large cohort of healthy Koreans. Using permutational multivariate analysis of variance and prediction modeling, we examined associations between microbial profiles and metabolic variables including insulin, triglycerides, waist circumference and visceral fat. The strongest correlations were noted with specific enterotypes. Shotgun sequencing revealed that visceral fat is linked to the glycogen synthesis pathway influenced by Dorea longicatena and Bifidobacterium adolescentis. This suggests that these specific microbial signatures and their associated functional potential play a role in visceral fat-related obesity. To validate these findings, we conducted an in vivo study using diet-induced obesity mouse model. Oral administration of D. longicatena or B. adolescentis significantly promoted body weight gain and fat mass expansion and induced hepatic lipogenic gene upregulation. The prevalence of these strains in Korean and American populations highlights their global relevance, contributing to the development of personalized treatments and advanced health strategies.

Journal Article

Trimethylamine-producing microbe Bacillus megaterium KCTC 3007 promotes antitumor immunity in endometrial cancer via type I interferon response pathways.

BACKGROUND: Endometrial cancer (ECa) is one of the most common gynecologic malignancies, with limited therapeutic responses in metastatic or recurrent cases. The bacterial microbiota has emerged as a key modulator of carcinogenesis and antitumor immunity. However, the role of endometrial microbiota in ECa pathogenesis and prognosis remains poorly understood. METHODS: We performed comprehensive multi-omics analysis integrating metatranscriptomics, transcriptomics, and targeted metabolomics from 60 ECa and 18 benign patients. RNA sequencing enabled simultaneous profiling of active tissue-resident microbiota and host gene expression. Serum metabolomics was conducted on all patients. Identified microbial-metabolite associations were validated through in vitro co-culture experiments using peripheral blood mononuclear cells (PBMCs), cancer cell lines, RNA sequencing, and live cell imaging. RESULTS: ECa patients exhibited significantly altered microbial diversity and composition compared to benign controls. Through integrated multi-omics analysis, we identified Bacillus megaterium (BM) KCTC 3007 as a beneficial microbe associated with prolonged recurrence-free survival. In an exploratory analysis of ECa subtypes, Cupriavidus taiwanensis and Marinomonas primoryensis showed potential links to poor prognosis, although these observations warrant caution due to the limited size of certain subgroups. Tissue BM abundance positively correlated with serum trimethylamine N-oxide (TMAO) levels, particularly in postmenopausal women. In vitro experiments demonstrated that BM KCTC 3007 enhanced antitumor immunity by promoting interleukin and type I interferon expression, expanding CD8 + T cell populations, and increasing immune cell-tumor cell interactions. RNA sequencing revealed activation of interferon alpha response and immune cell proliferation pathways, with IFNAR1 identified as a key upstream regulator. TMAO treatment recapitulated these immune-activating effects, enhancing CD8 + T cell responses and preferentially inducing pyroptotic cancer cell death. CONCLUSIONS: We provide the first evidence that tissue-resident BM KCTC 3007 promotes antitumor immunity in ECa through TMAO production and subsequent type I interferon-mediated immune activation. This integrated multi-omics approach establishes a complete microbe-metabolite-host mechanistic pathway and highlights the therapeutic potential of TMAO-producing probiotic strains for ECa treatment. Video Abstract.

Female

Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.

The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers.

Adult