The Intestinal Microbiota in Colorectal Cancer

Tilg, Herbert; Adolph, Timon E.; Gerner, Romana R.; Moschen, Alexander R.

doi:10.1016/j.ccell.2018.03.004

Cited by 577 publications

(497 citation statements)

References 120 publications

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“…UC has a complex, multifactorial etiopathogenesis, including host genetic, environmental and microbial factors, which has not been fully elucidated. Recent in‐depth studies have found that gut microbiota—as a complex ecosystem—are associated with many diseases . Intestinal mucosal homeostasis is based on the physiological coexistence of an abundant and diverse commensal bacterial ecosystem that colonizes the intestine .…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

Guo

Liu

Hao

2020

J of Digest Diseases

173

110

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Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem—based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic‐associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.

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Section: Introductionmentioning

confidence: 99%

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

Guo

Liu

Hao

2020

J of Digest Diseases

173

110

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“…CRC development and outcome are thus largely influenced by the immune response and its microenvironment. In addition, a large amount of microorganisms are also present in this colonic tumor microenvironment and could play a role in carcinogenesis …”

Section: Introductionmentioning

confidence: 99%

“…Colorectal cancer patients often exhibit a distinct microbiota composition (dysbiosis) compared to that of a healthy population . Recently, Wong et al .…”

Section: Introductionmentioning

confidence: 99%

Colibactin‐positive Escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer

Lopès

Billard

Casse

et al. 2020

Intl Journal of Cancer

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Colibactin‐producing E. coli (CoPEC) are frequently detected in colorectal cancer (CRC) and exhibit procarcinogenic properties. Because increasing evidence show the role of immune environment and especially of antitumor T‐cells in CRC development, we investigated the impact of CoPEC on these cells in human CRC and in the APCMin/+ mice colon. T‐cell density was evaluated by immunohistochemistry in human tumors known for their CoPEC status. APCmin/+ mice were chronically infected with a CoPEC strain (11G5). Immune cells (neutrophils and T‐cell populations) were then quantified by immunofluorescent staining of the colon. The quantification of lymphoid populations was also performed in the mesenteric lymph nodes (MLNs). Here, we show that the colonization of CRC patients by CoPEC is associated with a decrease of tumor‐infiltrating T lymphocytes (CD3+ T‐cells). Similarly, we demonstrated, in mice, that CoPEC chronic infection decreases CD3+ and CD8+ T‐cells and increases colonic inflammation. In addition, we noticed a significant decrease in antitumor T‐cells in the MLNs of CoPEC‐infected mice compared to that of controls. Moreover, we show that CoPEC infection decreases the antimouse PD‐1 immunotherapy efficacy in MC38 tumor model. Our findings suggest that CoPEC could promote a procarcinogenic immune environment through impairment of antitumor T‐cell response, leading to tumoral resistance to immunotherapy. CoPEC could thus be a new biomarker predicting the anti‐PD‐1 response in CRC.

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“…Large metagenomic studies in human CRC linked certain microbiome signatures with the colorectal adenoma‐carcinoma sequence. Although dominant species in CRC carcinogenesis remain poorly defined, an important role of Fusobacterium nucleatum ( Fn ), Escherichia coli , and Bacteroides fragilis coming from experimental evidence is emerging . A striking example is our recent identification of the link between Fusobacterium nucleatum and the chemoresistance to CRC .…”

Section: Introductionmentioning

confidence: 99%

Synbindin deficiency inhibits colon carcinogenesis by attenuating Wnt cascade and balancing gut microbiome

Ren

et al. 2019

Intl Journal of Cancer

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The molecular mechanisms that control the development of colorectal cancer (CRC) remain poorly defined. Here we show Synbindin promoted CRC oncogenesis by activating Wnt signaling and altering gut microbiome. Synbindin upregulation in human CRCs was associated with poor patient prognosis. Intestine‐specific disruption of Synbindin balanced the disturbed gut microbiota and protected mice against tumor formation in the colitis‐associated cancer (CAC) model. The protective role was compromised after gut microbiota depletion. In host, increased goblet cells and mucin2 expression, together with increased intestinal epithelial cells (IECs) apoptosis and decreased epithelial proliferation were observed. Further transcriptomic sequencing identified Wnt signaling a major regulatory node downstream of Synbindin. Combined molecular and cellular characterizations revealed that Synbindin confers Disheveled‐3 (DVL3)‐based signalosome assembly and acts as a modular scaffold for DVL3 and Axin2 complex, orchestrating the intensity of Wnt signaling. These findings identify a critical role of Synbindin in gut microbiome composition and Wnt signaling activation in colorectal carcinogenesis, and highlight Synbindin as an adaptor protein with multifaceted roles.

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The Intestinal Microbiota in Colorectal Cancer

Cited by 577 publications

References 120 publications

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment

Colibactin‐positive Escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer

Synbindin deficiency inhibits colon carcinogenesis by attenuating Wnt cascade and balancing gut microbiome

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