Association Between Bacteremia From Specific Microbes and Subsequent Diagnosis of Colorectal Cancer

Kwong, Thomas N.Y.; Wang, Xiansong; Nakatsu, Geicho; Chow, Theodore; Tipoe, Timothy L.; Dai, Rudin Z W; Tsoi, Kelvin K.K.; Wong, Martin Cs; Tse, Gary; Chan, Matthew T.V.; Chan, Francis K.L.; Ng, Siew C.; Wu, William Ka Kei; Yu, Jun; Sung, Joseph J.Y.; Wong, Sunny H.

doi:10.1053/j.gastro.2018.04.028

Cited by 230 publications

(185 citation statements)

References 33 publications

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“…Therefore, we selected cancer-related bacteria from previous studies. [24][25][26] As showed in Figure 3a, Bacteroides fragilis, Peptostreptococcus, Parvimonas, Alloprevotella and Gemella are enriched in tumor samples with COL6A3, LRP1B, MUC16 or FLG mutations. The products of invaded bacteria activated tumor-associated myeloid cells and produced cytokine IL23.…”

Section: Identification Of a Novel Five-gene Signature For Crc Patienmentioning

confidence: 85%

“…32,33 Previous studies have confirmed that the dysregulated localization of gut commensal bacteria plays a crucial role in CRC progression. 24,36,37 TME modulatory alterations may shape immune cell infiltration into tumor tissue and the infiltration status has been confirmed to be associated with recurrence and cancerrelated death. 38,39 Our results revealed that mutations of COL6A3, LRP1B, MUC16 and FLG genes may lead to loss of barrier function or tight junction, translocation of gut bacteria and deregulation of extracellular related and immune response genes.…”

Section: Discussionmentioning

confidence: 99%

“…These differential expressed genes were significantly enriched in the extracellular related and immune response gene ontology (GO) terms (Supporting Information Table S9, Fig. [24][25][26] As showed in Figure 3a, Bacteroides fragilis, Peptostreptococcus, Parvimonas, Alloprevotella and Gemella are enriched in tumor samples with COL6A3, LRP1B, MUC16 or FLG mutations. MUC16 and FLG are both known mechanical barrier genes.…”

Section: Basic Information Of Patients and Identification Of Somatic mentioning

confidence: 93%

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High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment

Cui

et al. 2019

Intl Journal of Cancer

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The heterogeneities of colorectal cancer (CRC) lead to staging inadequately of patients' prognosis. Here, we performed a prognostic analysis based on the tumor mutational profile and explored the characteristics of the high-risk tumors. We sequenced 338 colorectal carcinomas as the training dataset, constructed a novel five-gene (SMAD4, MUC16, COL6A3, FLG and LRP1B) prognostic signature, and validated it in an independent dataset from The Cancer Genome Atlas (TCGA). Kaplan-Meier and Cox regression analyses confirmed that the five-gene signature is an independent predictor of recurrence and prognosis in patients with Stage III colon cancer. The mutant signature translated to an increased risk of death (hazard ratio = 2.45, 95% confidence interval = 1.15-5.22, p = 0.016 in our dataset; hazard ratio = 4.78, 95% confidence interval = 1.33-17.16, p = 0.008 in TCGA dataset). RNA and bacterial 16S rRNA sequencing of high-risk tumors indicated that mutations of the fivegene signature may lead to intestinal barrier integrity, translocation of gut bacteria and deregulation of immune response and extracellular related genes. The high-risk tumors overexpressed IL23A and IL1RN genes and enriched with cancer-related bacteria (Bacteroides fragilis, Peptostreptococcus, Parvimonas, Alloprevotella and Gemella) compared to the low-risk tumors. The signature identified the high-risk group characterized by gut bacterial translocation and upregulation of interleukins of the tumor microenvironment, which was worth further researching.

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Section: Identification Of a Novel Five-gene Signature For Crc Patienmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Basic Information Of Patients and Identification Of Somatic mentioning

confidence: 93%

See 1 more Smart Citation

High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment

Cui

et al. 2019

Intl Journal of Cancer

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“…is an emerging opportunistic pathogen responsible for septicemia and infective endocarditis in 4 elderly and immunocompromised individuals (1,2). This Gram-positive coccus is one of the few 5 intestinal bacteria that have been consistently linked to colorectal cancer (CRC) over the last 40 6 years (3) and a recent study confirms this suspicion (4). Whether Sgg is a driver and/or 7 passenger of CRC is the subject of recent studies and evidence for both models have been 8 obtained experimentally (5)(6)(7)(8)(9)(10).…”

Section: Introduction 1mentioning

confidence: 99%

Heterogeneous expression of Pil3 pilus is critical for Streptococcus gallolyticus translocation across polarized colonic epithelial monolayers

Martins

Merle

Trieu‐Cuot

et al. 2019

Preprint

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Running title: Pil3 heterogeneity critical for Sgg gut translocation ABSTRACT Streptococcus gallolyticus subspecies gallolyticus (Sgg) is an opportunistic pathogen responsible for septicaemia and endocarditis in elderly persons. Sgg is also a commensal of the human gastrointestinal tract. Here we demonstrate that Sgg strain UCN34 translocates across tight intestinal barriers in vitro in a Pil3-dependent manner. Confocal images of UCN34 passage across human colonic cells reveals that Sgg utilizes a paracellular pathway. Pil3 was previously shown to be expressed heterogeneously and WT UCN34 consists of about 90% of Pil3 low and 10% of Pil3 high cells. We found that both the ∆pil3 mutant and the Pil3+ overexpressing variant could not translocate across Caco-2 and T84 barriers. Interestingly, combining live ∆pil3 mutant cells with fixed Pil3+ variants in a 10:1 ratio (mimicking UCN34 WT population) allowed efficient translocation of the ∆pil3 mutant. These experiments demonstrate that heterogeneous expression of Pil3 plays a key role in optimal translocation of Sgg across the intestinal barrier. ABSTRACT IMPORTANCEStreptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathogen responsible for septicemia and infective endocarditis in elderly persons. Sgg is a commensal of the rumen of herbivores and transmission to humans most probably occurs through the oral route. In this work, we have studied how this bacterium crosses the intestinal barrier using well-known in vitro models. Confocal microscopy images revealed that Sgg UCN34 can traverse the epithelial monolayer in between adjacent cells. We next showed that passage of Sgg from the apical to the basolateral compartment is dependent on the heterogenous expression of the Pil3 pilus at the bacterial surface. We hypothesize that Pil3 high cocci adhere firmly to epithelial cells to activate transient opening of tight junctions thereby allowing the traversal of Pil3low bacteria.

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“…This suggested that it can contribute to inflammation and DNA methylation only in cooperation with the C. leptum subgroup. The promoting role of B. fragilis is supported by a study that subsequent risk of colorectal cancer increased among patients with bacteremia from B. fragilis,42 and also by a study showing that enterotoxigenic B. fragilis triggered colon carcinogenesis in a mouse model 43. Naturally, these bacteria include various genera and species, and a more detailed analysis is necessar y Changes in colonic microbiota with antibiotic treatment.…”

mentioning

confidence: 97%

Antibiotics suppress colon tumorigenesis through inhibition of aberrant DNA methylation in an azoxymethane and dextran sulfate sodium colitis model

Hattori¹,

Niwa²,

Ishida

et al. 2018

Cancer Science

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Chronic inflammation is involved in the development of colon cancer by inducing mutations and aberrant DNA methylation in colon epithelial cells. Furthermore, there is growing evidence that colonic microbiota modulates the inflammation response in the host and influences colon tumorigenesis. However, the influence of colonic microbiota on aberrant DNA methylation remains unknown. Here, we show the effect of colonic microbes on DNA methylation and tumorigenicity using a mouse model of human ulcerative colitis. Mice treated with azoxymethane (AOM) and dextran sulfate sodium (DSS) showed an increase in degree of colitis, as estimated by body weight, occult blood, and stool consistency/diarrhea at 2 weeks after treatment, but treatment with antibiotics markedly reduced the severity of the colitis. Although mucosal hyperplasia and increased inflammation‐related genes were observed in the colonic epithelial cells of the AOM/DSS‐treated mice, treatment with antibiotics abrogated these changes. In addition, treatment with antibiotics significantly decreased the number of mucosal nodules from 5.9 ± 5.3 to 0.2 ± 0.6 (P < .01) and area of occupancy from 50.1 ± 57.4 to 0.5 ± 1.4 mm2 (P < .01). Aberrant DNA methylation of three marker CpG islands (Cbln4, Fosb, and Msx1) was induced by AOM/DSS treatment in colonic mucosae, but this increase was suppressed by 50%‐92% (P < .05) with antibiotic treatment. Microbiome analysis showed that this change was associated with a decrease of the Clostridium leptum subgroup. These data indicate that antibiotics suppressed tumorigenesis through inhibition of aberrant DNA methylation induced by chronic inflammation.

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Association Between Bacteremia From Specific Microbes and Subsequent Diagnosis of Colorectal Cancer

Cited by 230 publications

References 33 publications

High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment

High‐risk Stage III colon cancer patients identified by a novel five‐gene mutational signature are characterized by upregulation of IL‐23A and gut bacterial translocation of the tumor microenvironment

Heterogeneous expression of Pil3 pilus is critical for Streptococcus gallolyticus translocation across polarized colonic epithelial monolayers

Antibiotics suppress colon tumorigenesis through inhibition of aberrant DNA methylation in an azoxymethane and dextran sulfate sodium colitis model

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