Intestinal inflammation targets cancer-inducing activity of the microbiota

By Janelle C. Arthur, E. Peréz-Chanona, Marcus Mühlbauer, Sarah Tomkovich, Joshua M Uronis, Ting-Jia Fan, B. Campbell, Turki Abujamel, B. Dogan, A. Rogers and 7 more. Science, 2012

2,116 citations recorded by the source corpus.

Of Microbes and Cancer Inflammation is a well-established driver of tumorigenesis. For example, patients with inflammatory bowel disease have an elevated risk of developing colorectal cancer (CRC). Whether the gut microbiota also contributes to the development of CRC is less well understood. Arthur et al. (p. 120, published online 16 August; see the Perspective by Schwabe and Wang) now show that the microbiota does indeed promote tumorigenesis in an inflammation-driven model of CRC in mice. Although germ-free mice were protected against developing cancer, colonization of mice with Escherichia coli was sufficient to drive tumorigenesis. Microbes resident in the gut can promote colorectal cancer in mice in an inflammation-independent manner. Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-susceptible interleukin-10–deficient (Il10−/−) mice. Monocolonization with the commensal Escherichia coli NC101 promoted invasive carcinoma in azoxymethane (AOM)–treated Il10−/− mice. Deletion of the polyketide synthase (pks) genotoxic island from E. coli NC101 decreased tumor multiplicity and invasion in AOM/Il10−/− mice, without altering intestinal inflammation. Mucosa-associated pks+ E. coli were found in a significantly high percentage of inflammatory bowel disease and CRC patients. This suggests that in mice, colitis can promote tumorigenesis by altering microbial composition and inducing the expansion of microorganisms with genotoxic capabilities.

Subfields: Genetics, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/c7790fbff216bef850657cdf3644715c9da27c3c

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In Genetics

1. G. Núñez
2. W. Zou
3. S. Bischoff
4. Patrick D. Schloss
5. F. Greten
6. Y. Belkaid
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8. M. Pateiro

In Molecular Biology

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2. M. Zeng
3. Nielson T. Baxter
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6. H. Gardner
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In Surgery

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6. Y. Belkaid
7. Herbert Tilg
8. T. Hand

Citations in the corpus

• Human gut microbiota in health and disease: Unveiling the relationship (2022, background): “Various preclinical studies using GF mice have proposed the mechanism and considerable impact of gut microbiota on genesis and cancer progression (Arthur et al., 2012).”
• The gut microbiota and host health: a new clinical frontier (2015, background): “Many microbiome studies have focused on colitis-associated cancers 83 or rodent preclinical models.”
• The microbiome and cancer (2018, background): “Genome instability and mutation Escherichia coli PKS producing calobactin that induces double-strand breaks Arthur et al (2012) [98]”
• Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy (2017, background): “The microbiota is linked to CRC initiation and progression via affecting intestinal inflammation (Arthur et al., 2012; Garrett, 2015; Man et al., 2015; Zitvogel et al., 2015) and tumor-related signaling pathways (Schwabe and Jobin, 2013).”
• Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin (2013, background): “Previous studies have provided mechanistic insights into the microbial involvement in the development of CRC (Arthur et al., 2012; Cuevas-Ramos et al., 2010; Lee et al., 2010; Wu et al., 2009).”
• Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance. (2016, background): “Obese and overweight subjects and obese mice have reduced prevalence of Firmicutes and enhanced prevalence of Bacteroidetes (6, 23, 25, 46, 98).”