Dissecting causal links between gut microbiota, inflammatory cytokines, and DLBCL: a Mendelian randomization study

Blood Advances, Journal Year: 2024, Volume and Issue: 8(9), P. 2268 - 2278

Published: March 20, 2024

Causal relationships between gut microbiota, inflammatory cytokines, and diffuse large B-cell lymphoma (DLBCL) remain elusive. In addressing this gap, our Mendelian randomization (MR) study used data from the MiBioGen consortium encompassing 211 microbiota taxa (n = 18 340), genome-wide association meta-analyses of 47 DLBCL cases controls FinnGen (cases, n 1010; controls, 287 137). Through bidirectional MR analyses, we examined causal links mediation including 2-step multivariable (MVMR), to identify potential mediating cytokines. Our findings revealed that 4 were causally associated with DLBCL, conversely, influenced abundance 20 taxa. Specifically, in analysis, both genus Ruminococcaceae UCG-002 (odds ratio [OR], 1.427; 95% confidence interval [CI], 1.011-2.015; P .043) cytokine monokine induced by gamma (MIG) (OR, 1.244; CI, 1.034-1.487; .020) found be an increased risk DLBCL. Additionally, a positive was observed MIG 1.275; 1.069-1.520; .007). Furthermore, MVMR analysis indicated mediated MIG, contributing 14.9% effect (P .005). conclusion, provides evidence supports relationship role played MIG.

Language: Английский

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Gut Microbiota Disruption in Hematologic Cancer Therapy: Molecular Insights and Implications for Treatment Efficacy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10255 - 10255

Published: Sept. 24, 2024

Hematologic malignancies (HMs), including leukemia, lymphoma, and multiple myeloma, involve the uncontrolled proliferation of abnormal blood cells, posing significant clinical challenges due to their heterogeneity varied treatment responses. Despite recent advancements in therapies that have improved survival rates, particularly chronic lymphocytic leukemia acute lymphoblastic treatments like chemotherapy stem cell transplantation often disrupt gut microbiota, which can negatively impact outcomes increase infection risks. This review explores complex, bidirectional interactions between microbiota cancer patients with HMs. Gut influence drug metabolism through mechanisms such as production enzymes bacterial β-glucuronidases, alter efficacy toxicity. Moreover, microbial metabolites short-chain fatty acids modulate host immune response, enhancing effectiveness. However, therapy reduces diversity beneficial bacteria, Bifidobacterium Faecalibacterium, while increasing pathogenic bacteria Enterococcus Escherichia coli. These findings highlight critical need preserve during treatment. Future research should focus on personalized microbiome-based therapies, probiotics, prebiotics, fecal transplantation, improve quality life for hematologic malignancies.

Language: Английский

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Causal Associations of Gut Microbiota Species With Lymphoma: A Two‐Sample Mendelian Randomization Study

Hematological Oncology, Journal Year: 2025, Volume and Issue: 43(2)

Published: Feb. 14, 2025

This study aims to focus on GM at species level, exploring the causal associations with different kinds of lymphoma provide some information potential intervention directions in lymphoma. Data taxa were extracted from genome-wide association conducted by MiBioGen and Dutch Microbiome Project (DMP), those lymphomas obtained FinnGen consortium. Inverse variance weighted (IVW) method Bonferroni multiple correction utilized assess The effect size was expressed odds ratios (ORs) 95% confidence intervals (CIs). Reverse analysis has also been performed. Additionally, scatter plots leave-one-out test for sensitivity analysis. After correction, IVW estimates suggested that elevated relative abundance Faecalibacterium_prausnitzii had a negatively increased Hodgkin's (HL) (OR = 0.584, CI: 0.516-0.662). Relative Gordonibacter_pamelaeae, Holdemania_filiformis, Sutterella_wadsworthensis Coprococcus_sp_ART55_1 associated follicular (FL) odds, whereas Bifidobacterium_catenulatum Coprococcus_comes positively FL (all p < 0.05). Akkermansia_muciniphila non-follicular (NFL) respectively, while Bacteroides_uniformis positive one Flavonifractor_plautii linked diffuse large B-cell (DLBCL) risk 0.471, 0.344-0.645). Eggerthella_unclassified T/NK cell (TNK) Ruminococcus_lactaris TNK Elevated Parabacteroides_unclassified higher non-Hodgkin's (NHL) 1.955, 1.654-2.312). Holdemania_filiformis mantle (MCL) 0.637, 0.544-0.746). Rothia_mucilaginosa Lachnospiraceae_bacterium_3_1_46FAA marginal zone (MZL) risk, Alistipes_senegalensis negative identified 16 have lymphoma, which provided new idea further exploration prevention treatment targets

Language: Английский

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Changes in Vitamin D and Gut Microbiota in Pediatric Hematopoietic Stem Cell Transplantation Patients with Bloodstream Infections

International Journal for Vitamin and Nutrition Research, Journal Year: 2025, Volume and Issue: 95(1)

Published: Feb. 12, 2025

Background: Vitamin D (VD) and gut microbiota (GM) are important variables in pediatric hematopoietic stem cell transplantation (HSCT) recipients with bloodstream infections (BSI). Both VD GM play significant roles immune regulation maintaining intestinal barrier function. Methods: This prospective case-control study included 48 consecutive patients who underwent HSCT, as well 20 healthy children from the community. Plasma samples were collected pre- post-HSCT, together post-HSCT fecal samples. Serum 25-hydroxyvitamin (25(OH)D) 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) measured using chemiluminescence enzyme linked immunosorbent assay, respectively. was analyzed by 16S rDNA next generation sequencing. Results: The incidence of BSI HSCT 33.3% (16/48). No differences serum 25(OH)D or 1,25(OH)2D3 levels observed between non-BSI groups either before after transplantation, control group. α-diversity significantly lower than subjects. Proteobacteria more abundant (p = 0.0434) controls 0.0193). Pediatric showed higher Staphylococcus < 0.001), Pseudomonas Enterococcus Clostridium innocuum 0.0175) Enterobacter 0.0394) compared to controls, whereas Firmicutes 0.009), Actinobacteria Bifidobacterium 0.001) Faecalibacterium lower. β-diversity analysis revealed population three groups. Conclusions: These results indicate there is no practical value monitoring patients. During BSI, experiences a loss probiotics an increase potential pathogens.

Language: Английский

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Identification of intratumoral microbiome-driven immune modulation and therapeutic implications in diffuse large B-cell lymphoma

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(4)

Published: March 3, 2025

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, with significant clinical heterogeneity. Recent studies suggest that intratumoral microbiome may influence tumor microenvironment, affecting patient prognosis and therapeutic responses. This study aims to identify microbiome-related subtypes in DLBCL assess their impact on prognosis, immune infiltration, sensitivity. Transcriptomic data from 48 patients were obtained public databases. Consensus clustering was used classify into distinct subtypes. Functional enrichment analysis, infiltration assessments, single-cell RNA sequencing performed explore biological characteristics these Drug sensitivity predictions made using OncoPredict tool. Hub genes' expression function validated inferred cell lines independent cohorts DLBCL. Two identified. Patients Cluster 1 exhibited significantly better overall survival (P < 0.05), higher regulatory T cells M0 macrophages compared 2, which associated poorer outcomes. analysis revealed genes involved pathways, including cytokine-cytokine receptor interactions chemokine signaling, suggesting enhanced anti-tumor In contrast, 2 enriched immunosuppressive contributing a less favorable prognosis. Single-cell heterogeneity populations within microenvironment. B notable heterogeneity, as indicated by stemness differentiation potential scoring. Intercellular communication demonstrated played key role interactions, differences observed MIF signaling between subgroups. Pseudo-time further trajectories cells, highlighting across different environments. Metabolic pathway showed average levels metabolic pathways among subgroups, functional specialization. Furthermore, interaction core microbiome-driven differentially expressed identified nine (GSTM5, LURAP1, LINC02802, MAB21L3, C2CD4D, MMEL1, TSPAN2, CITED4), found play critical roles influenced microbiome. MMEL1 CITED4 important biologically classification. demonstrates prognostic significance DLBCL, identifying activity, The findings provide insights focusing dynamics. These results lay foundation for microbiome-based biomarkers personalized treatment approaches, ultimately aiming enhance outcomes

Language: Английский

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Microbiota-reprogrammed phosphatidylcholine inactivates cytotoxic CD8 T cells through UFMylation via exosomal SerpinB9 in multiple myeloma

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 24, 2025

Gut microbiome influences tumorigenesis and tumor progression through regulating the microenvironment (TME) modifying blood metabolites. However, mechanisms by which gut metabolites regulate TME in multiple myeloma (MM) remain unclear. By employing16S rRNA gene sequencing coupled with metagenomics ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, we find that Lachnospiraceae are high phosphatidylcholine (PC) low MM patients. We further show inhibits PC production from cells enhances cytotoxic CD8 T cell function. Mechanistically, promotes Sb9 mRNA maturation LIN28A/B via lysophosphatidic acid, thus exosamal production. Exosamal then reduces GZMB expression suppressing protein p53 (TP53) UFMylation competitive binding of TP53 ubiquitin-fold modifier conjugating enzyme 1 cells. may be potential therapeutic targets for treatment. The mechanism Here authors can suppress production, latter inhibiting function elicited exosomal SerpinB9 myeloma.

Language: Английский

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The Gut Connection: Exploring the Possibility of Implementing Gut Microbial Metabolites in Lymphoma Treatment

Cancers, Journal Year: 2024, Volume and Issue: 16(8), P. 1464 - 1464

Published: April 11, 2024

Recent research has implicated the gut microbiota in development of lymphoma. Dysbiosis microbial community can disrupt production metabolites, thereby impacting host physiology and potentially contributing to Dysbiosis-driven release metabolites such as lipopolysaccharides promote chronic inflammation, elevating risk In contrast, short-chain fatty acids, have shown promise preclinical studies by promoting regulatory T-cell function, suppressing preventing Another metabolite, urolithin A, exhibited immunomodulatory antiproliferative properties against lymphoma cell lines vitro. While on role is limited, this article emphasizes need comprehend their significance, including therapeutic applications, molecular mechanisms action, interactions with standard chemotherapies. The also suggests promising directions for future emerging field connection between microbiome.

Language: Английский

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The effect of intermittent fasting on microbiota as a therapeutic approach in obesity

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: April 25, 2024

Obesity, a public health challenge, arises from complex interplay of factors such as dietary habits and genetic predisposition. Alterations in gut microbiota, characterized by an imbalance between Firmicutes Bacteroidetes, further exacerbate metabolic dysregulation, promoting inflammation disturbances. Intermittent fasting (IF) emerges promising strategy showing efficacy weight management favoring fat utilization. Studies have used mice animal models to demonstrate the impact IF on microbiota composition, highlighting enhanced metabolism reduced inflammation. In humans, preliminary evidence suggests that promotes healthy profile, with increased richness abundance beneficial bacterial strains like Lactobacillus Akkermansia . However, clinical trials are necessary validate these findings elucidate long-term effects obesity. Future research should focus specific tissues cells, use advanced -omics techniques, exploring interaction other patterns, analyze gene expression, potential synergistic for health. While supports benefits obesity regulation, diverse populations robust methodologies is understand its implications optimize personalized interventions. This review explores intricate relationship Specifically, we will elucidating underlying mechanisms through which affects well subsequent

Language: Английский

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The gastrointestinal mycobiome in inflammation and cancer: unraveling fungal dysbiosis, pathogenesis, and therapeutic potential

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(6)

Published: May 5, 2025

Language: Английский

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Gut microbial dysbiosis in the pathogenesis of leukemia: an immune-based perspective

Experimental Hematology, Journal Year: 2024, Volume and Issue: 133, P. 104211 - 104211

Published: March 26, 2024

Language: Английский

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