Temozolomide-Induced Changes in Gut Microbial Composition in a Mouse Model of Brain Glioma

Li, Xiaochong; Wu, Bang‐Sheng; Jiang, Yi; Li, Jie; Wang, Xinghuan; C, Ma; Li, Yirong; Yao, Jie; Jin, Xiaoqing; Li, Zhiqiang

doi:10.2147/dddt.s298261

Cited by 18 publications

(19 citation statements)

References 35 publications

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“…The results showed that the development of glioma in mice led to a decrease in the abundance of Bacteroidetes, which was mainly composed of S24-7, and an increase in the abundance of Firmicutes including Clostridia_Clostridiales, Clostridiales_Lachnospiraceae, and Oscillospira. Anthony Patrizz and Xiao-Chong Li et al observed that glioma growth led to biological dysbiosis of GM in mice, with the most significant changes in Bacteroidetes and Firmicutes (19,20), which was consistent with our results.…”

Section: Discussionsupporting

confidence: 92%

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Gut Microbiome Alterations Affect Glioma Development and Foxp3 Expression in Tumor Microenvironment in Mice

Fan

Chen

et al. 2022

Front. Oncol.

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Glioma is the most common malignant tumor of the central nervous system (CNS), with high degree of malignancy and poor prognosis. The gut microbiome (GM) is composed of microorganisms with different properties and functions, which play an important role in human physiology and biological activities. It has been proved that GM can affect the development of glioma through natural immunity, but whether GM can affect glioma through adaptive immunity and whether there are some microorganisms in the GM that may affect glioma growth still remain unclear. In our study, we evaluated the relationship between GM and glioma. We proved that (I) glioma growth can induce structural changes of mouse GM, including the decreased abundance of Bacteroidia and increased abundance of Firmicutes. (II) GM dysbiosis can downregulate Foxp3 expression in the brain and promote glioma growth. A balanced environment of GM can upregulate the expression of Foxp3 in the brain and delay the development of glioma. (III) The increased abundance of Bacteroidia is associated with accelerated glioma progression, while its decreased abundance is associated with delayed glioma progression, which may be one of the key microorganisms affecting glioma growth. This study is helpful to reveal the relationship between GM and glioma development and provide new ideas for adjuvant therapy of glioma.

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Section: Discussionsupporting

confidence: 92%

“…Anthony Patrizz and Xiao-Chong Li et al. observed that glioma growth led to biological dysbiosis of GM in mice, with the most significant changes in Bacteroidetes and Firmicutes ( 19 , 20 ), which was consistent with our results.…”

Section: Discussionsupporting

confidence: 92%

Gut Microbiome Alterations Affect Glioma Development and Foxp3 Expression in Tumor Microenvironment in Mice

Fan

Chen

et al. 2022

Front. Oncol.

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“…Looking specifically to glioma, antibiotic treatment through a gut microbiome-immune cells-microglia circuit oriented to a pro-inflammatory pathway leads to increased glioma growth in mice models (52). Moreover, a different gut microbiome diversity was shown in mice and glioma patients as compared with healthy subjects and temozolomide was able to restore the pattern found in physiological conditions (53,54).…”

Section: Gut Microbiome Gut-brain Axis and Kd: A Broadband Connection Still To Explorementioning

confidence: 99%

A Root in Synapsis and the Other One in the Gut Microbiome-Brain Axis: Are the Two Poles of Ketogenic Diet Enough to Challenge Glioblastoma?

et al. 2021

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Glioblastoma is the most frequent and aggressive brain cancer in adults. While precision medicine in oncology has produced remarkable progress in several malignancies, treatment of glioblastoma has still limited available options and a dismal prognosis. After first-line treatment with surgery followed by radiochemotherapy based on the 2005 STUPP trial, no significant therapeutic advancements have been registered. While waiting that genomic characterization moves from a prognostic/predictive value into therapeutic applications, practical and easy-to-use approaches are eagerly awaited. Medical reports on the role of the ketogenic diet in adult neurological disorders and in glioblastoma suggest that nutritional interventions may condition outcomes and be associated with standard therapies. The acceptable macronutrient distribution of daily calories in a regular diet are 45–65% of daily calories from carbohydrates, 20–35% from fats, and 10–35% from protein. Basically, the ketogenic diet follows an approach based on low carbohydrates/high fat intake. In carbohydrates starvation, body energy derives from fat storage which is used to produce ketones and act as glucose surrogates. The ketogenic diet has several effects: metabolic interference with glucose and insulin and IGF-1 pathways, influence on neurotransmission, reduction of oxidative stress and inflammation, direct effect on gene expression through epigenetic mechanisms. Apart from these central effects working at the synapsis level, recent evidence also suggests a role for microbiome and gut-brain axis induced by a ketogenic diet. This review focuses on rationales supporting the ketogenic diet and clinical studies will be reported, looking at future possible perspectives.

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“…Lyu Y et al and D’Alessandro G et al observed that by influencing the immune system and modulating neurotransmitters, the crosstalk between intestinal flora and the brain could lead to the formation and development of gliomas [ 14 , 15 ]. This hypothesis was validated by Patrizz A et al [ 16 ] and Xiaochong L et al [ 17 ] in rat experiments, while a human study by Yuqi W [ 18 ] proved that oral microbiota is associated with the malignancy of brain tumors. To our knowledge, the composition of intestinal flora is significantly affected by oral microbiota [ 19 ].…”

Section: Introductionmentioning

confidence: 76%

The role of gut microbiota in patients with benign and malignant brain tumors: a pilot study

et al. 2022

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Gut microbiota is associated with the growth of various tumors, including malignant gliomas, through the brain-gut axis. Moreover, the gut microbiota in patients with malignant tumors may considerably differ from those with benign tumors. However, the associations of gut microbiota with benign and malignant brain tumors remain unclear. Hence, in order to explore these underlying relationships, patients with benign meningioma (n = 32), malignant glioma (n = 27), and healthy individuals (n = 41) were selected to participate in this study. The results showed that the diversity of the microbial ecosystem in brain tumor patients were less than the healthy controls, while no significant differences were observed between the meningioma and glioma groups. The microbial composition also differed significantly between individuals with brain tumors and healthy participants. In meningioma group, pathogenic bacteria like Enterobacteriaceae were increased , whereas certain carcinogenic bacteria were overrepresented in the glioma group, including Fusobacterium and Akkermansia . Furthermore, benign and malignant brain tumor patients lacked SCFA-producing probiotics. Thus , a microbial biomarker panel including Fusobacterium, Akkermansia, Escherichia/Shigella, Lachnospira, Agathobacter , and Bifidobacterium was established. Diagnostic models confirmed that this panel could distinguish between brain tumor patients and healthy patients. Additionally, gut microbiota can affect the differentiation and proliferation of brain tumors via several metabolic pathways based on annotations from the Kyoto Encyclopedia of Genes and Genomes (KEGG). This is the first study designed to investigate whether gut microbiota differs between benign and malignant brain tumor patients, and our work concluded that intestinal flora is a valuable tool for the diagnosis and treatment of brain tumors.

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Temozolomide-Induced Changes in Gut Microbial Composition in a Mouse Model of Brain Glioma

Cited by 18 publications

References 35 publications

Gut Microbiome Alterations Affect Glioma Development and Foxp3 Expression in Tumor Microenvironment in Mice

Gut Microbiome Alterations Affect Glioma Development and Foxp3 Expression in Tumor Microenvironment in Mice

A Root in Synapsis and the Other One in the Gut Microbiome-Brain Axis: Are the Two Poles of Ketogenic Diet Enough to Challenge Glioblastoma?

The role of gut microbiota in patients with benign and malignant brain tumors: a pilot study

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