Lactobacillus intestinalis facilitates tumor-derived CCL5 to recruit dendritic cell and suppress colorectal tumorigenesis

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 8, 2025

Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, deep mechanism between microbiota-TME interaction has not been well explored. In this study, we for first time discovered that Lactobacillus intestinalis (L. intestinalis) effectively suppressed growth both AOM/DSS-induced CRC model and ApcMin/+ spontaneous adenoma model. Our investigation revealed L. increased infiltration immune cells, particularly dendritic cells (DC), TME. Mechanically, tumor-derived CCL5 induced by recruited DC chemotaxis through NOD1/NF-κB signaling pathway. clinical samples datasets, found positive correlation intestinalis, level, DC-related genes. study provided new strategy microbial intervention deepened understanding modulated gut microbes.

Language: Английский

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Bifidobacterium adolescentis orchestrates CD143⁺ cancer‐associated fibroblasts to suppress colorectal tumorigenesis by Wnt signaling‐regulated GAS1

Cancer Communications, Journal Year: 2023, Volume and Issue: 43(9), P. 1027 - 1047

Published: Aug. 2, 2023

Abstract Background The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is not well explored. Here, we elucidated functional role Bifidobacterium adolescentis ( B.a ) on CRC investigated its possible mechanism manipulation cancer‐associated fibroblasts (CAFs) CRC. Methods Different animal models various cell line were established to explore function single‐cell RNA sequencing (scRNA‐seq) or flow cytometry was used detect subsets TME Western blot, quantitative real‐time polymerase chain reaction (qRT‐PCR), immunofluorescence staining performed examine activation Wnt signaling growth arrest specific 1 (GAS1) CD143 + CAFs. Chromatin immunoprecipitation PCR (CHIP‐qPCR) investigate regulation transcription factor 4 (TCF4) GAS1. Multi‐immunofluorescence assay examined expression level GAS1 tissue microarray. Results We found that abundance significantly reduced patients from two independent cohorts bacteria database GMrepo. Supplementation with suppressed Apc Min/+ spontaneous AOM/DSS‐induced tumorigenesis mice. scRNA‐seq revealed facilitated a subset CAFs by inhibiting infiltration Th2 cells, while promoting TNF‐alpha B cells TME. highly expressed exhibited suppressive effect. Mechanistically, activated Wnt/β‐catenin correlated predicted better survival outcome patients. Conclusions These results highlighted induced new signaling‐regulated suppress provided novel therapeutic target for probiotic‐based modulation

Language: Английский

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The role of the gut microbiota in tumor, immunity, and immunotherapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 5, 2024

In recent years, with the deepening understanding of gut microbiota, it has been recognized to play a significant role in development and progression diseases. Particularly gastrointestinal tumors, microbiota influences tumor growth by dysbiosis, release bacterial toxins, modulation host signaling pathways immune status. Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment efficacy enhancing cell responses. Current clinical preclinical studies demonstrated that its metabolites can enhance effectiveness immunotherapy. Furthermore, certain serve as biomarkers for predicting immunotherapy Interventions targeting diseases, especially colorectal (CRC), include fecal transplantation, probiotics, prebiotics, engineered bacteria, dietary interventions. These approaches not only improve ICIs but also hold promise outcomes. this review, we primarily discuss immunity,

Language: Английский

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The role of cancer-associated fibroblasts in the invasion and metastasis of colorectal cancer

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 30, 2024

Colorectal cancer (CRC) is the third most common and has ranked leading cause in cancerassociated death globally. Metastasis of colorectal patients. The role tumor microenvironment (TME) metastasis received increasing attention. As abundant cell type TME solid tumors, cancer-associated fibroblasts (CAFs) have been demonstrated to multiple functions advancing growth metastasis. They can remodel extracellular matrix (ECM) architecture, promote epithelial-mesenchymal transition (EMT), interact with cells or other stromal by secreting factors, cytokines, chemokines, exosomes, facilitating invasion into contributing distant This article aims analyze sources heterogeneity CAFs CRC, as well their metastasis, order provide new insights mechanism CRC its clinical applications.

Language: Английский

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Helicobacter pylori CagA elevates FTO to induce gastric cancer progression via a “hit‐and‐run” paradigm

Cancer Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Background Helicobacter pylori ( H. ) infection contributes significantly to gastric cancer (GC) progression. The intrinsic mechanisms of ‐host interactions and their role in promoting GC progression need further investigation. In this study, we explored the potential fat mass obesity‐associated protein (FTO) mediating Cytotoxin‐associated gene A (CagA)‐induced Methods effects on N 6 ‐methyladenosine (m A) modification were evaluated both human samples cell lines. function FTO was elucidated through vitro vivo studies. series techniques, including methylated RNA immunoprecipitation sequencing, binding immunoprecipitation, chromatin assays, utilized investigate mechanism by which mediates capacity cagA ‐positive promote Furthermore, therapeutic inhibitor meclofenamic acid (MA) impeding across cells, animal models, organoids. Results Infection with upregulated expression , essential for CagA‐mediated metastasis associated a poor prognosis patients. Mechanistically, CagA delivered enhanced transcription via Jun proto‐oncogene. Elevated induced demethylation m inhibited degradation heparin‐binding EGF‐like growth factor (HBEGF), thereby facilitating epithelial‐mesenchymal transition (EMT) process cells. Interestingly, eradication did not fully reverse increases HBEGF levels . However, treatment combination antibiotics MA substantially ‐induced EMT prevented metastasis. Conclusion Our study revealed that “hit‐and‐run” CagA‐induced progression, suggests targeting could offer promising approach prevention

Language: Английский

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The causal relationship between gut microbiota and lymphoma: a two-sample Mendelian randomization study

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 7, 2024

Previous studies have indicated a potential link between the gut microbiota and lymphoma. However, exact causal interplay two remains an area of ambiguity.

Language: Английский

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Gut microbiome: decision-makers in the microenvironment of colorectal cancer

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Dec. 12, 2023

Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, accounting for second most cause tumors. As one intestinal barriers, gut bacteria form biofilm, participate in work, and living environment cells. Metagenomic next-generation sequencing (mNGS) large number CRC patients has been established, enabling specific microbial signatures to be associated with colorectal adenomato-carcinoma. Gut are involved both benign precursor lesions (polyps), situ growth metastasis CRC. Therefore, term tumorigenic was proposed 2018, such as Escherichia coli , Fusobacterium nucleatum enterotoxigenic Bacteroides fragilis etc. Meanwhile, toxins (such cytolethal distending toxin (CDT), Colibactin (Clb), B. toxin) affect tumor microenvironment promote occurrence immune escape. It important note that there differences different types In this paper, role polyp-cancer transformation effects their secreted on will discussed, thereby further exploring new ideas prevention treatment

Language: Английский

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Gene prediction of immune cells association between gut microbiota and colorectal cancer: a Mendelian randomization study

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 31, 2025

An increasing number of studies have revealed that gut microbiota influences the development and progression Colorectal cancer (CRC). However, whether a causal relationship exists between two remains unclear, role immune cells in this context is not well understood. To elucidate CRC to explore potential mediating circulating cells. analyze CRC, we employed univariable Mendelian randomization (UVMR) approach. Subsequently, two-step multivariable (MVMR) assess Primarily, applied Inverse-Variance Weighted method evaluate exposure outcome. ensure robustness results linking validated findings using Robust Weighted, Penalized methods. Additionally, MR-Egger Intercept mitigate influence horizontal pleiotropy. MR-PRESSO was used detect correct outliers by excluding anomalous instrumental variables. Finally, supplemented our analysis with methods such as Bayesian Randomization (BWMR), Maximum-Likelihood, Lasso, Debiased Inverse Variance Contamination Mixture establish robust compelling relationship. After accounting for reverse causality, pleiotropy, various methodological corrections, Bifidobacterium kashiwanohense, GCA-900066755 sp900066755, Geminocystis, Saccharofermentanaceae exhibited strong effects on CRC. Specifically, CD40 monocytes (2.82%) CD45 CD33+HLA-DR+CD14- (12.87%) mediated kashiwanohense risk. Furthermore, CD33-HLA-DR+ (3.94%) sp900066755 terminally differentiated CD4+T (11.55%) Geminocystis Lastly, (2.35%), central memory (5.76%), CD28 CD28+CD45RA+CD8+T (5.00%) Our mediation MR provides genetic evidence suggesting may mediate The identified associations offer new insights into therapeutic avenues

Language: Английский

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Progress of mesenchymal stem cells affecting extracellular matrix metabolism in the treatment of female stress urinary incontinence

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 25, 2025

Stress urinary incontinence (SUI) is a prevalent pelvic floor dysfunction in women post-pregnancy. Currently, conservative treatment options have low success rates, while surgical interventions often result multiple complications. The altered state of the extracellular matrix (ECM) pivotal factor onset various diseases and likely plays significant role pathogenesis SUI, particularly through changes collagen elastin levels. Recent advances mesenchymal stem cells (MSCs) therapy shown considerable promise treating SUI by modulating ECM remodeling, thereby enhancing supportive tissues female floor. MSCs exhibit substantial potential urethral sphincter function, connective tissue architecture, stimulating fibroblast activity. They play reconstruction functional recovery influencing signaling pathways, including TGF-β/SMAD, JAK/STAT, Wnt/β-catenin, PI3K/AKT, ERK/MAPK. We reviewed advancements MSC-mediated metabolism and, integrating functions other how can ameliorate conditions their impact on metabolism, we projected future trajectory development.

Language: Английский

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Gut dysbiosis conveys psychological stress to activate LRP5/β-catenin pathway promoting cancer stemness

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 5, 2025

Psychological stress causes gut microbial dysbiosis and cancer progression, yet how microbiota determines psychological stress-induced tumor development remains unclear. Here we showed that promotes breast growth stemness, an outcome depends on in germ-free antibiotic-treated mice. Metagenomic metabolomic analyses revealed markedly alters the composition abundance of microbiota, especially Akkermansia muciniphila (A. muciniphila), decreases short-chain fatty acid butyrate. Supplement active A. muciniphila, butyrate or a butyrate-producing high fiber diet dramatically reversed oncogenic property anxiety-like behavior murine spontaneous model orthotopic model. Mechanistically, RNA sequencing analysis screened out LRP5 expression to block activation Wnt/β-catenin signaling pathway, dampening stemness. Moreover, as HDAC inhibitor elevated histone H3K9 acetylation level transcriptionally activate ZFP36, which further accelerates mRNA decay by binding adenine uridine-rich (AU-rich) elements transcript. Clinically, fecal serum were inversely correlated with tumoral LRP5/β-catenin expression, poor prognosis negative mood patients. Altogether, our findings uncover microbiota-dependent mechanism stress-triggered provide both clinical biomarkers potential therapeutic avenues for patients undergoing stress.

Language: Английский

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