Human Gut Microbiome and Risk for Colorectal Cancer

Ahn, Jiyoung; Sinha, Rashmi; Pei, Zhiheng; Dominianni, Christine; Wu, Jing; Shi, Jianxin; Goedert, James J.; Hayes, Richard B.; Yang, Liying

doi:10.1093/jnci/djt300

Cited by 805 publications

(700 citation statements)

References 26 publications

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“…As shown in Fig. 3B, Upper, the alpha diversity decreased drastically (50% on average) in all groups after 38 d. This loss of community diversity can be explained by the tumor-induced dysbiosis in the gut bacteria community, consistent with previous findings that some diseases could lead to an imbalanced gut microbiota and decrease the ecological diversity in the gut (21,22). When comparing the alpha diversity between the 38-d samples, we observed no significant difference between the control and ProTreat groups; however, cisplatin and ProPre groups showed significantly higher alpha diversity than both the control and ProTreat (Bonferroni adjusted P value < 0.05, Wilcoxon rank-sum test using 100 bootstrap samples).…”

Section: Probiotics Mediate the Structural And Functional Compositionsupporting

confidence: 89%

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Sung

Lee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

501

386

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The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotictreated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment.H epatocellular carcinoma (HCC) is one of the most common cancers, the sixth most common neoplasm, and the second most deadly type of cancer worldwide (1). The traditional HCC treatment, including surgical treatment, local ablation therapy, and chemotherapy, could offer potential cure, yet patients are facing many limitations including the poor hepatic reserve. HCC is clearly a disease for which alternative therapeutic strategies must be developed. A better understanding of the interactions between cancer cells and stromal components in the tumorassociated proinflammatory microenvironment would be important for the management of this disease.The tumor microenvironment is infiltrated with various immune cells such as T cells, macrophages, neutrophils, natural killer (NK) cells, and myeloid-derived suppressor cells. Inflammation is known to play a pivotal role in tumor development by escalating tumor angiogenesis and cell growth. Once a solid tumor is formed, inflammation arises in the tumor-promoting direction. At the same time, new vasculature is needed in the tumor to provide nutrients and oxygen to support the growth of cancer cells, and this process plays a critical role in HCC, a highly vascularized tumor (2). Inflammation and angiogene...

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Section: Probiotics Mediate the Structural And Functional Compositionsupporting

confidence: 89%

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Sung

Lee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

501

386

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“…Recent studies have shown that Fusobacterium, especially Fusobacterium nucleatum (Fn), is associated with colorectal cancer. Fn is enriched in both the feces and colonic mucosa of colorectal cancer patients (3,5,8) and plays important roles in colorectal carcinogenesis (9,10). In our recent study, using 16S rRNA sequencing to catalog the microbial communities in human gut mucosa at different stages of colorectal tumorigenesis, Fusobacterium was also found to be enriched in colorectal tumors (11).…”

Section: Introductionmentioning

confidence: 93%

“…These candidates were identified by eliminating confounding effects of colonoscopy using blocked independent Wilcoxon rank-sum tests with colonoscopy as a stratifying factor in our previous metagenome study (12). Fn has also been identified to be enriched in colorectal cancer patients by others (3,5,8), while the other four have not associated with colorectal cancer by other researchers. Primer and probe sequences targeting the nusG gene of Fn (Accession# GMHS-1916) and gene markers identified by our previous metagenome sequencing study, including Bc (ID 370640), Ch (ID 2736705), Ri (ID 181682), and m7 (ID 3246804; ref.…”

Section: Design Of Primers and Probesmentioning

confidence: 99%

“…Abnormality in the composition of the gut microbiota has been implicated as a potentially important etiologic factor in the initiation and progression of colorectal cancer (2). With the widespread application of metagenome sequencing and pyrosequencing in the investigation of intestinal microbiota, an increasing number of bacteria have been identified to be positively associated with the incidence of colorectal cancer (3)(4)(5)(6)(7). Recent studies have shown that Fusobacterium, especially Fusobacterium nucleatum (Fn), is associated with colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

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Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

Liang

Chiu

Chen

et al. 2017

Clinical Cancer Research

264

251

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Purpose: Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for colorectal cancer diagnosis.Experimental Design: Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.Results: Candidates identified by metagenome sequencing, including Fusobacterium nucleatum (Fn), Bacteroides clarus (Bc), Roseburia intestinalis (Ri), Clostridium hathewayi (Ch), and one undefined species (labeled as m7), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (r ¼ 0.801-0.934, all P < 0.0001). Fn was significantly more abundant in colorectal cancer than controls (P < 0.0001), with AUROC of 0.868 (P < 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity, Fn discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (Fn þ Ch þ m7-Bc) showed an improved diagnostic ability compared with Fn alone (AUROC ¼ 0.886, P < 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of Fn alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.Conclusions: Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.

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“…Although this study did not imply a more diverse microbiota is 'preferable' in terms of health, others have certainly implied this through association [60][61][62]. Such conclusions, regardless of the different tools used to acquire the data, should also be treated with caution.…”

Section: Effects Of Diets On the Gut Microbiota In Five Continentsmentioning

confidence: 67%

The Effects of Diet and the Microbiome on Reproduction and Longevity: A Comparative Review Across 5 Continents

Chilton¹,

Enos

Burton

et al. 2014

J Nutr Food Sci

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Human Gut Microbiome and Risk for Colorectal Cancer

Cited by 805 publications

References 26 publications

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

The Effects of Diet and the Microbiome on Reproduction and Longevity: A Comparative Review Across 5 Continents

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