Gut microbiota composition in chemotherapy and targeted therapy of patients with metastatic colorectal cancer

Chen, Yen-Cheng; Chuang, Chia-Hsien; Zhang, Miao; Yip, Kwan-Ling; Liu, Chung‐Jung; Li, Ling-Hui; Wu, Deng‐Chyang; Cheng, Tian−Lu; Lin, Chung‐Yen; Wang, Jaw‐Yuan

doi:10.3389/fonc.2022.955313

Cited by 17 publications

(13 citation statements)

References 76 publications

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“…Although studies with more diverse populations and larger sample sizes are required to determine whether population-specific bacteria are responsible for CRC progression and are associated with clinicopathological characteristics, our results strongly suggest that P. intermedia and F. nucleatum are critical pathogens for CRC development in individuals of Han Chinese origin. Moreover, our recent study demonstrated that F. nucleatum is closely associated with treatment outcomes in patients with metastatic CRC receiving chemotherapy and targeted therapy [41].…”

Section: Discussionmentioning

confidence: 94%

Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas

Jao

et al. 2022

J Biomed Sci

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Background Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. Methods Microbiota composition was determined through 16S rRNA V3–V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as “tri-part samples”) in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. Results Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. Conclusion This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.

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Section: Discussionmentioning

confidence: 94%

Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas

Jao

et al. 2022

J Biomed Sci

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“…In addition, chemotherapy (5-fluorouracil/oxaliplatin) markedly increases the ratio of relative abundance of the Firmicutes/Bacteroidetes, inducing greater disturbance of intestinal microbiota ( Chang et al, 2020 ). Although the gut microbiota of patients who had a partial response for targeted therapy (bevacizumab/cetuximab) exhibits significantly higher α-diversity than that of the progressive disease group, the overall intestinal microbiota is still disordered ( Chen et al, 2022 ). Alteration in the intestinal microbiota affects the metabolic pathway of glycerophospholipid, thereby regulating the therapeutic potential of the immunotherapy (PD-1 antibody) in MSS-type CRC tumor-bearing mice ( Xu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses

Han

et al. 2023

Front. Microbiol.

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Many lines of evidence demonstrate the associations of colorectal cancer (CRC) with intestinal microbial dysbiosis. Recent reports have suggested that maintaining the homeostasis of microbiota and host might be beneficial to CRC patients, but the underlying mechanisms remain unclear. In this study, we established a CRC mouse model of microbial dysbiosis and evaluated the effects of fecal microbiota transplantation (FMT) on CRC progression. Azomethane and dextran sodium sulfate were used to induce CRC and microbial dysbiosis in mice. Intestinal microbes from healthy mice were transferred to CRC mice by enema. The vastly disordered gut microbiota of CRC mice was largely reversed by FMT. Intestinal microbiota from normal mice effectively suppressed cancer progression as assessed by measuring the diameter and number of cancerous foci and significantly prolonged survival of the CRC mice. In the intestine of mice that had received FMT, there were massive infiltration of immune cells, including CD8+ T and CD49b+ NK, which is able to directly kill cancer cells. Moreover, the accumulation of immunosuppressive cells, Foxp3+ Treg cells, seen in the CRC mice was much reduced after FMT. Additionally, FMT regulated the expressions of inflammatory cytokines in CRC mice, including down-regulation of IL1a, IL6, IL12a, IL12b, IL17a, and elevation of IL10. These cytokines were positively correlated with Azospirillum_sp._47_25, Clostridium_sensu_stricto_1, the E. coli complex, Akkermansia, Turicibacter, and negatively correlated with Muribaculum, Anaeroplasma, Candidatus_Arthromitus, and Candidatus Saccharimonas. Furthermore, the repressed expressions of TGFb, STAT3 and elevated expressions of TNFa, IFNg, CXCR4 together promoted the anti-cancer efficacy. Their expressions were positively correlated with Odoribacter, Lachnospiraceae-UCG-006, Desulfovibrio, and negatively correlated with Alloprevotella, Ruminococcaceae UCG-014, Ruminiclostridium, Prevotellaceae UCG-001 and Oscillibacter. Our studies indicate that FMT inhibits the development of CRC by reversing gut microbial disorder, ameliorating excessive intestinal inflammation and cooperating with anti-cancer immune responses.

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“…Even so, the previous study has also shown that the Bifidobacterium genus accumulated in ankylosing spondylitis patients [ 17 ]. Another study investigated the role of the gut microbiota in the treatment outcomes of patients with metastatic CRC (mCRC) and reported that Lactobacillus and Bifidobacterium species exhibited higher abundance in the progressive disease (PD) group than in the partial response (PR) group [ 28 ]. Additionally, some Bacteroides species have been demonstrated to exhibit significantly lower relative abundance in patients with UC than in healthy controls [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

A novel promising diagnosis model for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene biomarkers

Zheng²,

Yang

et al. 2022

Cell Biosci

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Background Colorectal cancer (CRC), a commonly diagnosed cancer often develops slowly from benign polyps called adenoma to carcinoma. Altered gut microbiota is implicated in colorectal carcinogenesis. It is warranted to find non-invasive progressive microbiota biomarkers that can reflect the dynamic changes of the disease. This study aimed to identify and evaluate potential progressive fecal microbiota gene markers for diagnosing advanced adenoma (AA) and CRC. Results Metagenome-wide association was performed on fecal samples from different cohorts of 871 subjects (247 CRC, 234 AA, and 390 controls). We characterized the gut microbiome, identified microbiota markers, and further constructed a colorectal neoplasms classifier in 99 CRC, 94 AA, and 62 controls, and validated the results in 185 CRC, 140 AA, and 291 controls from 3 independent cohorts. 21 species and 277 gene markers were identified whose abundance was significantly increased or decreased from normal to AA and CRC. The progressive gene markers were distributed in metabolic pathways including amino acid and sulfur metabolism. A diagnosis model consisting of four effect indexes was constructed based on the markers, the sensitivities of the Adenoma Effect Index 1 for AA, Adenoma Effect Index 2 for high-grade dysplasia (HGD) adenoma were 71.3% and 76.5%, the specificities were 90.5% and 90.3%, respectively. CRC Effect Index 1 for all stages of CRC and CRC Effect Index 2 for stage III–IV CRC to predict CRC yielded an area under the curve (AUC) of 0.839 (95% CI 0.804–0.873) and 0.857 (95% CI 0.793–0.921), respectively. Combining with fecal immunochemical test (FIT) significantly improved the sensitivity of CRC Effect Index 1 and CRC Effect Index 2 to 96.7% and 100%. Conclusions This study reports the successful diagnosis model establishment and cross-region validation for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene markers. The results suggested that the novel diagnosis model can significantly improve the diagnostic performance for advanced adenoma.

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Gut microbiota composition in chemotherapy and targeted therapy of patients with metastatic colorectal cancer

Cited by 17 publications

References 76 publications

Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas

Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas

Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses

A novel promising diagnosis model for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene biomarkers

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