Deciphering the Colorectal Cancer Gut Microbiota: Association vs. Causality

Bridges, Kristina M.; Greiner, K. Allen; Umar, Shahid

doi:10.1007/s11888-019-00431-5

Cited by 6 publications

(3 citation statements)

References 71 publications

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“…Microorganisms drive the initiation and progression of approximately 15–20% human cancers [ 1 ]. There are approximately 100 trillion bacteria in the intestine, including >1000 different species [ 2 ]. Recently, researchers have focused on the relationship between the gut microbiota and cancer, including modulation of the release of inflammatory mediators, alterations of the immune microenvironment, and interaction with metabolism [ 3 – 5 ].…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide promotes metastasis via acceleration of glycolysis by the nuclear factor-κB/snail/hexokinase3 signaling axis in colorectal cancer

Qian

Zhang

et al. 2021

Cancer Metab

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Background Cancer cell is generally characterized by enhanced glycolysis. Inflammasome activation is interaction with glycolysis. The concentration of lipopolysaccharide (LPS), a classic inflammasome activator, is significantly higher in colorectal cancer tissue than in normal intestinal mucosa. However, the mechanism of LPS on glycolysis and metastasis has not been fully elucidated. This study aimed to investigate the roles of LPS on inflammasome activation, glycolysis, and metastasis, and unravel metformin’s potential in treatment of CRC. Methods We detected inflammasome activation and cell motility following LPS exposure in CRC cell lines. Glycolysis analysis was performed, and the key glycolytic rate-limiting enzymes were detected. Dual-luciferase reporter gene assay, co-immunoprecipitation, chromatin immunoprecipitation (ChIP) analysis, and ChIP-reChIP assay were performed to identify the specific mechanisms of LPS on glycolysis. Mouse metastasis models were used to determine the effects of LPS and metformin on metastasis. Correlation analysis of the expression of various molecules was performed in 635 CRC samples from The Cancer Genome Atlas and 83 CRC samples from our lab. Results LPS activates caspase-1 through NF-κB and upregulates the expression of Snail and HK3 depending on caspase-1 activation. LPS potentiates migration and invasion depending on accelerated glycolysis, which could be reversed by knockdown of glycolytic rate-limiting enzyme HK3. Nuclear Snail is upregulated by NF-κB under LPS treatment and then forms a complex with NF-κB, then directly binds to the HK3 promoter region to upregulate the expression of HK3. Metformin suppresses the NF-κB/Snail/HK3 signaling axis that is activated by LPS and then inhibits LPS-induced metastasis. In vivo, LPS-treated cells form more metastasis in the lungs of mice, and metformin completely reverses this effect of LPS. Conclusion LPS activates inflammasomes in cancer cells through NF-κB and promotes metastasis through glycolysis enhanced by the NF-κB/Snail/HK3 signaling pathway in CRC. Metformin could prevent this effect of LPS.

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Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide promotes metastasis via acceleration of glycolysis by the nuclear factor-κB/snail/hexokinase3 signaling axis in colorectal cancer

Qian

Zhang

et al. 2021

Cancer Metab

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“…In summary, the above studies demonstrate that, like CRC, colorectal adenomas commonly harbor an altered microbiome compared to healthy mucosa. Whether this is cause or effect remains a matter of much debate [ 123 , 124 ]. Key findings from analyses of bowel polyp mucosa ( Table 2 ) suggest a relative enrichment of bacteria from the phylum Proteobacteria, particularly the orders Pseudomonodales (e.g., genus Pseudomonas ), Enterobacterales (e.g., genera Escherichia-Shigella , Klebsellia ) and Campylobacterales (e.g., genus Helicobacter ) in adenoma cases compared to controls.…”

Section: Microbiota and Colorectal Polypsmentioning

confidence: 99%

Genomic, Microbial and Immunological Microenvironment of Colorectal Polyps

Tse

Welham

Engel

et al. 2021

Cancers

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Colorectal cancer (CRC) develops from pre-cancerous cellular lesions in the gut epithelium, known as polyps. Polyps themselves arise through the accumulation of mutations that disrupt the function of key tumour suppressor genes, activate proto-oncogenes and allow proliferation in an environment where immune control has been compromised. Consequently, colonoscopic surveillance and polypectomy are central pillars of cancer control strategies. Recent advances in genomic sequencing technologies have enhanced our knowledge of key driver mutations in polyp lesions that likely contribute to CRC. In accordance with the prognostic significance of Immunoscores for CRC survival, there is also a likely role for early immunological changes in polyps, including an increase in regulatory T cells and a decrease in mature dendritic cell numbers. Gut microbiotas are under increasing research interest for their potential contribution to CRC evolution, and changes in the gut microbiome have been reported from analyses of adenomas. Given that early changes to molecular components of bowel polyps may have a direct impact on cancer development and/or act as indicators of early disease, we review the molecular landscape of colorectal polyps, with an emphasis on immunological and microbial alterations occurring in the gut and propose the potential clinical utility of these data.

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“…By this logic, taxa that increase in their importance in the network of CRC patients could be the “driver” taxa, moving beyond enriched abundance. Furthermore, according to the “driver-passenger” model, the CRC driver taxa could be superseded by “passenger” bacteria that are better adapted to the conditions in and around carcinoma cells, thereby outcompeting the initial driver species ( Feng et al., 2015 ; Bridges et al., 2019 ). For these reasons, a systematic analysis of CRC-associated bacteria along CRC progression is required from an ecological prospective, rather than case-control study.…”

Section: Introductionmentioning

confidence: 99%

Tumor bacterial markers diagnose the initiation and four stages of colorectal cancer

Cai

Xiong²,

Sha³

et al. 2023

Front. Cell. Infect. Microbiol.

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Increasing evidence has supported dysbiosis in the faecal microbiome along control-adenoma-carcinoma sequence. In contrast, the data is lacking for in situ tumor bacterial community over colorectal cancer (CRC) progression, resulting in the uncertainties of identifying CRC-associated taxa and diagnosing the sequential CRC stages. Through comprehensive collection of benign polyps (BP, N = 45) and the tumors (N = 50) over the four CRC stages, we explored the dynamics of bacterial communities over CRC progression using amplicons sequencing. Canceration was the primarily factor governing the bacterial community, followed by the CRC stages. Besides confirming known CRC-associated taxa using differential abundance, we identified new CRC driver species based on their keystone features in NetShift, including Porphyromonas endodontalis, Ruminococcus torques and Odoribacter splanchnicus. Tumor environments were less selective for stable core community, resulting in heterogeneity in bacterial communities over CRC progression, as supported by higher average variation degree, lower occupancy and specificity compared with BP. Intriguingly, tumors could recruit beneficial taxa antagonizing CRC-associated pathogens at CRC initiation, a pattern known as “cry-for-help”. By distinguishing age- from CRC stage-associated taxa, the top 15 CRC stage-discriminatory taxa contributed an overall 87.4% accuracy in diagnosing BP and each CRC stage, in which no CRC patients were falsely diagnosed as BP. The accuracy of diagnosis model was unbiased by human age and gender. Collectively, our findings provide new CRC-associated taxa and updated interpretations for CRC carcinogenesis from an ecological perspective. Moving beyond stratifying case-control, the CRC-stage discriminatory taxa could add the diagnosis of BP and the four CRC stages, especially the patients with poor pathological feature and un-reproducibility between two observers.

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Deciphering the Colorectal Cancer Gut Microbiota: Association vs. Causality

Cited by 6 publications

References 71 publications

Lipopolysaccharide promotes metastasis via acceleration of glycolysis by the nuclear factor-κB/snail/hexokinase3 signaling axis in colorectal cancer

Lipopolysaccharide promotes metastasis via acceleration of glycolysis by the nuclear factor-κB/snail/hexokinase3 signaling axis in colorectal cancer

Genomic, Microbial and Immunological Microenvironment of Colorectal Polyps

Tumor bacterial markers diagnose the initiation and four stages of colorectal cancer

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