Gut Microbiota Alteration Influences Colorectal Cancer Metastasis to the Liver by Remodeling the Liver Immune Microenvironment

Ni, Yuan; Li, Xiaoyan; Wang, Meng; Zhang, Zhilin; Lu, Qiao; Gao, Yamei; Xu, Xinjian; Zhi, Jie; Li, Yang; Li, Zhongxin; Jia, Yitao

doi:10.5009/gnl210177

Cited by 21 publications

(13 citation statements)

References 44 publications

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“…vaginae . Supplementation of Proteus mirabilis could promote CLM in mice by diminishing the proportion of Kupffer cells in the liver ( 60 ). In vitro experiments further proved that P. mirabilis promoted CRC cell migration by repressing Kupffer cell proliferation.…”

Section: The Gut Microbiota and Innate Immunitymentioning

confidence: 99%

The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes

et al. 2023

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The gastrointestinal tract is inhabited by trillions of commensal microorganisms that constitute the gut microbiota. As a main metabolic organ, the gut microbiota has co-evolved in a symbiotic relationship with its host, contributing to physiological homeostasis. Recent advances have provided mechanistic insights into the dual role of the gut microbiota in cancer pathogenesis. Particularly, compelling evidence indicates that the gut microbiota exerts regulatory effects on the host immune system to fight against cancer development. Some microbiota-derived metabolites have been suggested as potential activators of antitumor immunity. On the contrary, the disequilibrium of intestinal microbial communities, a condition termed dysbiosis, can induce cancer development. The altered gut microbiota reprograms the hostile tumor microenvironment (TME), thus allowing cancer cells to avoid immunosurvelliance. Furthermore, the gut microbiota has been associated with the effects and complications of cancer therapy given its prominent immunoregulatory properties. Therapeutic measures that aim to manipulate the interplay between the gut microbiota and tumor immunity may bring new breakthroughs in cancer treatment. Herein, we provide a comprehensive update on the evidence for the implication of the gut microbiota in immune-oncology and discuss the fundamental mechanisms underlying the influence of intestinal microbial communities on systemic cancer therapy, in order to provide important clues toward improving treatment outcomes in cancer patients.

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Section: The Gut Microbiota and Innate Immunitymentioning

confidence: 99%

The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes

et al. 2023

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“…After co-culture with Proteus vulgaris and Proteus mirabilis , SNAI1 and VIM gene expressions had changed significantly in human colon cancer cell line Caco2, which are related to epithelial mesenchymal transformation, thus it was suggested that Proteus may be correlated with the epithelial mesenchymal transformation of CRC [ 21 ]. Moreover, increased abundance of Proteus mirabilis played a key role in the liver metastasis of CRC, which may count on the reduction of Kupffer cells in the liver [ 22 ]. Parabacteroides was observed to be distinctly higher in abundance in CRC tissues than normal mucosa adjacent to cancer [ 23 ], besides, CRC patients with high Parabacteroides expression in gut had observably poorer prognosis than CRC patients with low Parabacteroides expression in gut [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of colorectal cancer progression-associated intestinal microbiome and predictive signature construction

et al. 2023

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Objective The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC. Method The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing. Result The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O − glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV. Conclusions The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O − glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction.

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“…Yuan N et al. ( 21 ) demonstrated that alterations in gut microbiota composition could remodel the liver immune microenvironment by regulating Kupffer cells (KCs) on colorectal cancer, promoting or inhibiting liver metastases. Alice Bertocchi et al.…”

Section: Discussionmentioning

confidence: 99%

The difference of human gut microbiome in colorectal cancer with and without metastases

Sun

Zhu²,

Jia³

et al. 2022

Front. Oncol.

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Metastasis of colorectal cancer is deemed to be closely related to the changes in the human gut microbiome. The purpose of our study is to distinguish the differences in gut microbiota between colorectal cancer with and without metastases. Firstly, this study recruited colorectal cancer patients who met the established inclusion and exclusion criteria in the Oncology Department of Zhejiang Hospital of Traditional Chinese Medicine from February 2019 to June 2019. Fresh stool samples from healthy volunteers, non-metastatic patients, and metastatic patients were collected for 16S rRNA gene sequencing, to analyze the diversity and abundance of intestinal microorganisms in each group. The results showed that the microbial composition of the control group was more aplenty than the experimental group, while the difference also happened in the Tumor and the metastases group. At the phylum level, the abundance of Bacteroidetes significantly declined in the Tumor and the metastases group, compared with the control group. At the class level, Bacilli increased in experimental groups, while its abundance in the Tumor group was significantly higher than that in the metastases group. At the order level, the Tumor group had the highest abundance of Lactobacillales, followed by the metastases group and the control group had the lowest abundance. Overall, our study showed that the composition of the flora changed with the occurrence of metastasis in colorectal cancer. Therefore, the analysis of gut microbiota can serve as a supplement biological basis for the diagnosis and treatment of metastatic colorectal cancer which may offer the potential to develop non-invasive diagnostic tests.

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Gut Microbiota Alteration Influences Colorectal Cancer Metastasis to the Liver by Remodeling the Liver Immune Microenvironment

Cited by 21 publications

References 44 publications

The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes

The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes

Identification of colorectal cancer progression-associated intestinal microbiome and predictive signature construction

The difference of human gut microbiome in colorectal cancer with and without metastases

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