Butyrate-producing Eubacterium rectale suppresses lymphomagenesis by alleviating the TNF-induced TLR4/MyD88/NF-κB axis

Lu, Haiyang; Xu, Xiaoqiang; Fu, Di; Gu, Yubei; Fan, Rong; Yi, Hongmei; He, Xiangyi; Wang, Chaofu; Ouyang, Binshen; Zhao, Ping; Wang, Li; Xu, Pengpeng; Cheng, Shu; Wang, Zhifeng; Zou, Duowu; Han, Lizhong; Zhao, Wei‐Li

doi:10.1016/j.chom.2022.07.003

Cited by 85 publications

(51 citation statements)

References 54 publications

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“…However, in certain situations, such as when the TET2 gene is deleted, translocation of probiotic Lactobacillus reuteri may lead to PMP, which may induce leukogenesis [ 15 ]. In lymphoma, deficiency of probiotics Eubacterium recale may increase the incidence rate of lymphoma, while supplementation with it may reduce lymphomagenesis [ 38 ]. The supplementation of probiotic Lactobacillus johnsonii may reduce the incidence of lymphoma in cases of A-T [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…The metabolite productions generated by intestinal microbes contribute to the alteration of plasma glucose concentrations and amino acid metabolism, resulting in tumor growth [ 18 , 44 , 53 , 54 ]. The activation of the immune system is usually caused by direct contact between intestinal immune cells and microbial metabolites, which activates TLR4/MyD88/NF-kB signaling in B cells [ 38 ] and the immune response, and promotes the progression of hematological malignancies. Specific intestinal microbes are conducive to the differentiation of Th17 cells, which migrate to bone marrow and further promote the eos-Th17-tumor cell positive-feedback loop [ 47 ] and sustain the progression of hematological malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…However, in the GI tract, a Eubacterium rectale -deficient gut microbiota stimulated B cells through enhanced TNF release and further sensitized B cells to LPS; these extracellular substances could bind to membrane TNFR1 and TLR4 and activate NF-kB signaling in a MyD88-dependent manner, as an extrinsic mechanism. These findings reveal the mechanism of inflammation-related lymphoma and the potential clinical principle of intestinal microbiota therapy targeting [ 38 ].…”

Section: Lymphomamentioning

confidence: 99%

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Intestinal Microbes and Hematological Malignancies

Zhu

Yang

et al. 2023

Cancers

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Hematological malignancies are diverse, with high malignancy characteristics, poor prognoses, and high mortality rates. The development of hematological malignancies is driven by genetic factors, tumor microenvironment factors, or metabolic factors; however, even when considering all of these factors, one still cannot fully estimate the risk of hematological malignancies. Several recent studies have demonstrated an intimate connection between intestinal microbes and the progression of hematological malignancies, and gut microbes play a primary role in the initiation and progression of hematological tumors through direct and indirect mechanisms. Thus, we summarize the correlation between intestinal microbes and hematological malignancies’ onset, progression, and therapeutic effect in order to better understand how intestinal microbes affect their initiation and progression, especially in leukemia, lymphoma, and multiple myeloma, which may provide potential therapeutic targets for improving the survival of patients with hematological malignancies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Lymphomamentioning

confidence: 99%

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Intestinal Microbes and Hematological Malignancies

Zhu

Yang

et al. 2023

Cancers

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“…(i) Jian et al reported that some nitrogen-recycling GMs such as Klebsiella and Streptococcus can provide a nitrogen source to meet the energy requirements of MM cells for L-glutamine(Gln) synthesis and rapid proliferation, thereby accelerating MM (Jian et al, 2020). (ii) GMs have been shown in studies to alter the levels of gut-derived metabolites such as short-chain fatty acids (SCFAs), which can suppress the secretion of in ammatory cytokines and the activation of nuclear factor κB signaling pathways, resulting in lower the levels of in ammatory factors in the bone marrow microenvironment and the suppression of the progression of hematologic malignancies (Lu et al, 2022). (iii) In addition, it was found that GMs facilitated the progression of acute myeloid leukemia (AML) by modulating the intestinal barrier function via butyrate.…”

Section: Discussionmentioning

confidence: 99%

The causal relationship of gut microbiota in progression of seven common hematological malignancie

Wang

Yang

et al. 2023

Preprint

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Purpose: Evidence from observational researches and clinical trials showed the relationship between gut microbiomes (GMs) and hematological malignancies. Nevertheless, the causal role of GM taxa in development of hematological malignancies remains to be explored. Therefore, we aim to assess the causal links between 196 GM taxa and seven common hematological malignancies using the two-sample Mendelian randomization (MR) analyses. Methods: All datasets were derived from published genome-wide association studies (GWAS) statistics. The primary analysis was performed using random effects inverse variance weighted (IVW). To verify the robustness of the MR results, we performed several sensitivity analyses such as Egger intercept test, the Cochran Q test, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis. Results: We revealed the family Oxalobacteraceae would increase the risk of myeloid leukemia by the Bonferroni correction [odds ratio (OR): 2.08, 95% CI: 1.49, 2.90, p = 1.68E-05]. In addition, 22 nominally significant associations between genetic liability in GMs and hematological malignancies were also found (P < 0.05). Sensitivity analysis verified the robustness of the above causal relationships. Conclusion: This study confirms the causal relationship between GMs and hematological malignancies and may provide new insights to the mechanistic and clinical researches of GM-mediated hematological malignancies.

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“…Intestinal microecology is not only involved in host digestion, metabolism and energy conversion, but also provides the host with benefits, including strengthening intestinal integrity, regulating intestinal epithelial function, resisting pathogens, supporting lipid metabolism and angiogenesis ( 13 , 14 ). Intestinal microecology also influences tumor development by interfering with the immune system, inducing genetic mutations, causing chronic inflammation and disrupting the balance between cell proliferation and apoptosis ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

The gut microbiota correlate with the disease characteristics and immune status of patients with untreated diffuse large B-cell lymphoma

Lin

Mao²,

Jin³

et al. 2023

Front. Immunol.

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BackgroundGut microbiota characteristics in patients with diffuse large B-cell lymphoma (DLBCL) are reportedly different when compared with the healthy population and it remains unclear if the gut microbiota affects host immunity and clinical disease features. This research investigated the gut microbiota in patients with untreated DLBCL and analyzed its correlation with patient clinical characteristics, humoral, and cell immune status.MethodsThirty-five patients with untreated DLBCL and 20 healthy controls (HCs) were recruited to this study and microbiota differences in stool samples were analyzed by 16S rDNA sequencing. Absolute ratios of immune cell subset counts in peripheral blood were detected by flow cytometry and peripheral blood cytokine levels were detected by enzyme-linked immunosorbent assay. Relationships between changes in patient microbiomes and clinical characteristics, such as clinical stage, international prognostic index (IPI) risk stratification, cell origin, organ involved and treatment responses were investigated and correlations between differential microbiota and host immune indices were analyzed.ResultsThe alpha-diversity index of intestinal microecology in DLBCL patients was not significantly different when compared with HCs (P>0.05), nonetheless beta-diversity was significantly decreased (P=0.001). p_Proteobacteria were dominant in DLBCL, while p_Bacteroidetes abundance was significantly decreased when compared with HCs (P<0.05). Gut microbiota characteristics were identified that were associated with clinical features, such as tumor load, risk stratification and cell origin, and correlation analyses were performed between differential flora abundance associated with these clinical features and host immune status. The p_Firmicutes was positively correlated with absolute lymphocyte values, g_Prevotella_2 and s_un_g_Prevotella_2 were negatively correlated with absolute lymphocyte values, T cell counts and CD4 cell counts, while g_Pyramidobacter, s_un_g_Pyramidobacter, and f_Peptostreptococcaceae were negatively correlated with IgA.ConclusionsDominant gut microbiota, abundance, diversity, and structure in DLBCL were influenced by the disease, correlated with patient immune status and this suggested that the microecology-immune axis may be involved in regulating lymphoma development. In the future, it may be possible to improve immune function in patients with DLBCL by regulating the gut microbiota, improve treatment response rates and increase patient survival rates.

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Butyrate-producing Eubacterium rectale suppresses lymphomagenesis by alleviating the TNF-induced TLR4/MyD88/NF-κB axis

Cited by 85 publications

References 54 publications

Intestinal Microbes and Hematological Malignancies

Intestinal Microbes and Hematological Malignancies

The causal relationship of gut microbiota in progression of seven common hematological malignancie

The gut microbiota correlate with the disease characteristics and immune status of patients with untreated diffuse large B-cell lymphoma

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