Effect of Oral Administration of<i>Butyrivibrio fibrisolvens</i>MDT-1, a Gastrointestinal Bacterium, on 3-Methylcholanthrene-Induced Tumor in Mice

Ohkawara, Sou; Furuya, Hideki; Nagashima, Kousuke; Asanuma, Narito; Hino, Tsuneo

doi:10.1080/01635580701397608

Cited by 10 publications

(8 citation statements)

References 40 publications

(37 reference statements)

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“…In addition, we observed a trend for a positive correlation between Butyrivibrio and activated NK cells, which are involved in inhibiting the growth and metastasis of tumors [70][71][72]. These results are consistent with reports showing that the numbers of natural killer cells markedly increase in response to Butyrivibrio brisolvens (the main member of Butyrivibrio) [73], and that increased numbers of natural killer cells may contribute to the alleviation of carcinogenesis by B. brisolvens [74]. This is supported by our observations, since breast cancer patients with more abundant Butyrivibrio showed better prognosis.…”

Section: Discussionsupporting

confidence: 91%

The Tumor Microbiome Is Implicated in Breast Cancer Prognosis

Zhu

et al. 2021

SSRN Journal

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Background: Some breast cancer patients are prone to recurrence and metastasis. Increasing evidence suggests that the breast tissue contains a diverse population of bacteria, which may be modulating the risk of breast cancer development or progression. However, the extent of microbial contribution to the tumor immune microenvironment in breast cancer remains unknown. Here, we explored the potential in uence of the tumor microbiota on the local immune microenvironment and breast cancer prognosis.Methods: Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition and identi ed bacteria that were differentially abundant between breast cancer patients with recurrence or metastasis (R/M) and those without recurrence or metastasis (NRM). We performed total RNA sequencing in tumor tissues from patients in both groups to determine differentially expressed genes (DEGs). The landscape of tumor-in ltrating immune cells (TIICs) subtypes in the tumor immune microenvironment was analyzed using CIBERSORT, based on the gene expression pro ling of tumor tissues. Differences in the tumor microbiomes were then correlated with DEGs and differences in TIICs, in order to determine how microbial abundance may contribute to cancer progression.Results: Microbial alpha-diversity was higher in NRM patients than in R/M patients. The composition and functions of the tumor microbiome communities differed between the two groups. We found higher alpha-diversity, higher abundance of Ruminococcus, Butyrivibrio, and Deinococcus, and lower abundance of Microbacterium could serve as a predictor of better prognosis in breast cancer patients. We also found that 16 genes, including CD36, showed differential expression in NRM compared to R/M, and differences in the composition of TIICs were observed between the two groups. In addition, we observed that the different tumor microbiome pro les were associated with DEGs and differences in TIICs between the two groups.Conclusions: The tumor microbiome may affect the prognosis of breast cancer patients by in uencing the tumor immune microenvironment. Thus, the tumor microbiome may be a useful prognostic indicator. BackgroundMicrobes colonize areas that are directly exposed to the air and surroundings, including the mouth, nostrils, skin, stomach, and the gastrointestinal and urogenital tracts [1]. Viral or bacterial infection is the third highest contributor to the development of cancer [2,3]. It is estimated that 15-20% of malignancies are caused by microbial pathogens, and even more malignancies are related to alterations in microbial communities that colonize human tissues [3][4][5][6]. The microbiome is associated with a variety of malignancies, including gastric, colon, liver, lung, and skin cancers and lymphoma. Perhaps the strongest linkages so far have been found between gastric cancer and Helicobacter pylori, and between colon cancer and Fusobacterium [7][8][9][10][11][12]. The microbiome may contribute to carcinogenesis by inducing chronic in ammation, altering cellular processes, ...

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Section: Discussionsupporting

confidence: 91%

The Tumor Microbiome Is Implicated in Breast Cancer Prognosis

Zhu

et al. 2021

SSRN Journal

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“…6,32,33 Oral administration of viable intact B. fibrisolvens of the strain MDT-1 isolated from the rumen of Japanese native goats has been shown to increase the fecal butyrate concentration as a measure of large intestinal butyrate production in mice after five days (bacteria administered on days 0, 1, 3 and 5) and to alleviate the formation of colon cancer pre-stages after three weeks. 14 The same strain of B. fibrisolvens was also capable of alleviating the symptoms of dextran sodium sulphate-induced enterocolitis 15 and could delay and reduce the incidence of 3-methylcholanthrene-induced tumors in mice; 16 intestinal SCFA production was not reported in these two studies. The microbial composition and numbers of B. fibrisolvens MDT-1 in cecum digesta were also not reported in any of these studies, so it is not possible to assess whether the positive effect indeed could be ascribed to the actual increase in the number of bacteria in the large intestine due to the oral administration.…”

Section: Discussionmentioning

confidence: 98%

“…Oral infusion of live intact B. fibrisolvens MDT-1 increased the rate of butyrate production measured as the concentration in feces and alleviated the formation of aberrant crypt foci 14 (colon cancer prestages), dextran sodium sulphate-induced experimental enterocolitis 15 and delayed and reduced the 3-methylcholanthreneinduced tumor incidence in mice. 16 However, these studies did not report whether the administrated bacteria actually survived in a viable state to reach the large intestine.…”

Section: Introductionmentioning

confidence: 99%

A search for synbiotics: effects of enzymatically modified arabinoxylan and Butyrivibrio fibrisolvens on short-chain fatty acids in the cecum content and plasma of rats

et al. 2016

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Identification of dietary strategies to increase large intestinal production and absorption of short-chain fatty acids (SCFAs), especially butyrate, is of great interest due to the possible health promoting effects. We explored the effect of an enzymatically modified arabinoxylan-rich diet (EAXD) versus a Western-style control diet (WSD) low in dietary fiber with or without orally administrated Butyrivibrio fibrisolvens, a butyrate producer, on the SCFA pool in the cecal content and feces and the SCFA concentration in the blood of rats. The pool of acetate, butyrate and total SCFA was more than double in the cecal content from EAXD-fed rats compared with WSD-fed rats, and this was also reflected as an increase in portal plasma SCFA concentrations. Acetate, propionate and total SCFA concentrations were higher in mixed venous plasma following the EAXD. The number of B. fibrisolvens did not increase significantly in cecal content following administration of the bacteria. Furthermore, there was no interaction between the EAXD and B. fibrisolvens on the measured parameters.

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“…In ovarian cancer tumors and cell lines, local and systemic (sera and/or peritoneal) TNF levels inversely correlate with tumor grade and stage (Balkwill, 2009). In endometrial cancer, increased production of TNFRI and TNFRII are also linked to an increased risk for developing the disease (Ohkawara et al., 2007). In the ovarian cancer model, TNF‐α is an important component of a malignant cell‐autonomous network of inflammatory cytokines that include IL‐6, macrophage inhibitory factor (MIF), and VEGF (Kulbe et al., 2007), and experimentally, TNF‐α receptor activation increases ovarian cancer growth, metastatic potential, and resistance to chemotherapy (Balkwill, 2009).…”

Section: Discussionmentioning

confidence: 99%

The clinical significance of inflammatory cytokines in primary cell culture in endometrial carcinoma

et al. 2012

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Endometrial cancer is the most common malignancy of the female genital tract, and the incidence and mortality rates from this disease are increasing. Although endometrial carcinoma has been regarded as a tissue-specific disease mediated by female sex steroid pathways, considerable evidence implicates a role for an inflammatory response in the development and propagation of endometrial cancer. We hypothesized that if specific patterns of cytokine expression were found to be predictive of adverse outcome, then selective receptor targeting may be a therapeutic option. This study was therefore undertaken to determine the relationship between cytokine production in primary cell culture and clinical outcome in endometrial adenocarcinoma. Fresh endometrial tissues were fractionated into epithelial and stromal fractions and cultured. After 6–7 days, supernatants were collected and cells enumerated. Batched aliquots were assayed using ELISA kits specific for CSF-1, GMCSF, G-CSF, TNF-α, IL-6, IL-8, and VEGF. Data were compared using ANOVA, Fisher’s exact, and log rank tests. Increased epithelial VEGF production was observed more often in tumors with Type 2 variants (p = 0.039) and when GPR30 receptor expression was high ( p = 0.038). Although increased stromal VEGF production was detected more often in grade 3 endometrioid tumors ( p = 0.050), when EGFR expression was high ( p = 0.003), and/or when ER/PR expression was low ( p = 0.048), VEGF production did not correlated with overall survival (OS). Increased epithelial CSF-1 and TNF-α production, respectively, were observed more often in tumors with deep myometrial invasion ( p = 0.014) and advanced stage ( p = 0.018). Increased CSF-1 (89.5% vs. 42.9%, p = 0.032), TNF-α (88.9% vs. 42.9%, p = 0.032, and IL-6 (92.3% vs. 61.5%, p = 0.052) also correlated with low OS. In Cox multivariate models, CSF-1 was an independent predictor of low survival when stratified by grade ( p = 0.046) and histology ( p = 0.050), and TNF-α, when stratified by histology ( p = 0.037). In this study, high CSF-1, TNF-α, and IL-6 production rates identified patients at greatest risk for death, and may signify patients likely to benefit from receptor-specific therapy.

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Effect of Oral Administration ofButyrivibrio fibrisolvensMDT-1, a Gastrointestinal Bacterium, on 3-Methylcholanthrene-Induced Tumor in Mice

Cited by 10 publications

References 40 publications

The Tumor Microbiome Is Implicated in Breast Cancer Prognosis

The Tumor Microbiome Is Implicated in Breast Cancer Prognosis

A search for synbiotics: effects of enzymatically modified arabinoxylan and Butyrivibrio fibrisolvens on short-chain fatty acids in the cecum content and plasma of rats

The clinical significance of inflammatory cytokines in primary cell culture in endometrial carcinoma

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