Mucosal microbiota of intestinal polyps reveals putative biomarkers of colorectal cancer

Mangifesta, Marta; Mancabelli, Leonardo; Milani, Christian; Gaiani, Federica; de’Angelis, Nicola; de’Angelis, Gian Luigi; Sinderen, Douwe van; Ventura, Marco; Turroni, Francesca

doi:10.1038/s41598-018-32413-2

Cited by 145 publications

(107 citation statements)

References 73 publications

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“…Interestingly, mice with compromised GI defense system also had a reduced number of butyrate-producing bacteria, similar to our observations in the CF patients, who generally consume a high-fat diet [76]. The loss in abundance of butyrateproducing Ruminococcaceae has also been previously observed in CRC [59,77]. While the mechanism of Clostridium and Fusobacterium in tumorigenesis is yet to be defined, several studies have reported an increased presence of these two taxa in colon of CRC patients [78].…”

Section: Discussionsupporting

confidence: 87%

Interactions between the gut microbiome and host gene regulation in cystic fibrosis

et al. 2020

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Background: Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in the CFTR gene, leading to poor hydration of mucus and impairment of the respiratory, digestive, and reproductive organ functions. Advancements in medical care have led to markedly increased longevity of patients with cystic fibrosis, but new complications have emerged, such as early onset of colorectal cancer. Although the pathogenesis of colorectal cancer in cystic fibrosis remains unclear, altered host-microbe interactions might play a critical role. To investigate this, we characterized changes in the microbiome and host gene expression in the colonic mucosa of cystic fibrosis patients relative to healthy controls, and identified host gene-microbiome interactions in the colon of cystic fibrosis patients. Methods: We performed RNA-seq on colonic mucosa samples from cystic fibrosis patients and healthy controls to determine differentially expressed host genes. We also performed 16S rRNA sequencing to characterize the colonic mucosal microbiome and identify gut microbes that are differentially abundant between patients and healthy controls. Lastly, we modeled associations between relative abundances of specific bacterial taxa in the gut mucosa and host gene expression. Results: We find that 1543 genes, including CFTR, show differential expression in the colon of cystic fibrosis patients compared to healthy controls. These genes are enriched with functions related to gastrointestinal and colorectal cancer, such as metastasis of colorectal cancer, tumor suppression, p53, and mTOR signaling pathways. In addition, patients with cystic fibrosis show decreased gut microbial diversity, decreased abundance of butyrate producing bacteria, such as Ruminococcaceae and Butyricimonas, and increased abundance of other taxa, such as Actinobacteria and Clostridium. An integrative analysis identified colorectal cancer-related genes, including LCN2 and DUOX2, for which gene expression is correlated with the abundance of colorectal cancer-associated bacteria, such as Ruminococcaceae and Veillonella. Conclusions: In addition to characterizing host gene expression and mucosal microbiome in cystic fibrosis patients, our study explored the potential role of host-microbe interactions in the etiology of colorectal cancer in cystic fibrosis. Our results provide biomarkers that may potentially serve as targets for stratifying risk of colorectal cancer in patients with cystic fibrosis.

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Section: Discussionsupporting

confidence: 87%

Interactions between the gut microbiome and host gene regulation in cystic fibrosis

et al. 2020

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“…So, while these genera are signi cantly depleted in mucosal samples compared to stool, a signi cant difference in abundance between location remained. Bi dobacterium was previously shown to have anti-cancerogenic effects [73,[90][91][92][93]. Similar association with left-sided and low-grade tumours showed 2 tumour genera (Lachnospira, Gemella) and Methanobrevibacter.…”

Section: Tumour Crc Microbial Subtypesmentioning

confidence: 54%

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

Zwinsová¹,

Петров²,

Hrivňáková³

et al. 2020

Preprint

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BackgroundLong-term dysbiosis of the gut microbiome has a significant impact on the development, progression and the aggressiveness of colorectal cancer (CRC) and may explain part of the observed heterogeneity of the disease from phenotypic, prognostic and response to treatment perspectives. Although the shifts in gut microbiome in the normal-adenoma-carcinoma sequence have been described, the landscape of microbiome within CRC and its associations with clinical variables remain under-explored. ResultsWe performed 16S rRNA gene sequencing of paired tumour tissue, adjacent visually-normal mucosa and stool swabs of N=186 patients with stage 0-IV CRC to describe the tumour microbiome and its association with clinical variable and to derive tumour microbial subtypes.We identified new genera never previously associated with CRC tumour mucosa (Flavonifractor, Haemophilus, Howardella, Pseudomonas, Sutterella, Treponema 2) or CRC (Actinobacillus, Aggregatibacter, Bergeyella, Phocaeiola, Defluviitaleaceae UCG-011, Massilia, Tyzzerella 4). The bacteria residing on tumour-mucosa were dominated by genera belonging to (potential) oral pathogens. Based on tumour microbial profiles, we stratified CRC patients into three subtypes. The subtypes were significantly associated with prognostic factors such as tumor grade, primary tumour sidedness and TNM staging, with one subtype enriched in tumours with poor prognosis. Further, we inspected the associations of microbiome with clinical variables in a subtype-agnostic setting. The primary tumour-associated clinical variables predominantly correlated with tumour mucosal microbiome, while the presence of local and distant metastases was mostly associated with the stool microbiome.ConclusionsUnderstanding the interactions of the bacteria residing on tumour mucosa within different CRC tumour microbiome subtypes will help to better understand the underlying biological background of the heterogeneity of this disease. Indeed, the tumour microbiome is a possible source of additional integrative markers of CRC patients’ survival and prognosis. We found that CRC microbiome is strongly correlated with clinical variables, but these associations are dependent on the microbial environment (tumour mucosa, normal mucosa, stool). Our study thus identifies limitations of the usage of microbiome composition as marker of CRC progression, suggesting the need of combining several sampling sites (e.g. stool and tumour swabs).

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“…Further study is indicated for clarifying the roles of PPIs in the development of HPs. In addition, it has been reported that the dysbiotic microbiota is associated with the development of nasal and intestinal polyps (33)(34)(35)(36). The human stomach harbors a complex microbiota in the luminal cavity and mucosa.…”

Section: Discussionmentioning

confidence: 99%

Gastric hyperplastic polyps inversely associated with current Helicobacter�pylori infection

Wang

et al. 2020

Exp Ther Med

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The incidence of gastric hyperplastic polyps (HPs) has been on the rise in recent years. The contribution of Helicobacter pylori infection to this trend has remained to be elucidated. The present study aimed to explore the association between HPs and H. pylori in China, an area with a high infection rate of H. pylori. In order to study trends of HPs and H. pylori infection over the past decades, cases encountered from 2009 to 2018 were assessed and a total of 109,150 consecutive patients who underwent esophagogastroduodenoscopy at Qingdao Municipal Hospital (Qingdao, China) were enrolled. The incidence of HPs and the prevalence of H. pylori were determined and their correlation was explored. Gastric HPs were detected in 1,497 patients (1.6%) who received gastric biopsies. The incidence of HPs exhibited a rising trend, with a ~4-fold increase in the annual detection rate from 2009 to 2018. The prevalence of H. pylori infection was inversely associated with the prevalence of HPs (adjusted odds ratio, 0.66). The prevalence of H. pylori in the examined cohort decreased with time (r=-0.76, P=0.011). The decreasing trend of H. pylori infection was negatively correlated with the rising trend of HPs (r=-0.64, P=0.048), further indicating an inverse association between them. The difference in the prevalence of HPs between H. pylori-negative and-positive patients increased with age (r=0.80, P=0.018). The age-associated increase was slower in H. pylori-infected patients. The decline in H. pylori infection with time appeared to not be associated with the birth cohort effect, suggesting the decline was not caused by exposure to environmental factors during an early period of life. The present results indicated that the incidence of gastric HPs increased with the decline in H. pylori infection, demonstrating an inverse association between the occurrence of HPs and the infection.

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Mucosal microbiota of intestinal polyps reveals putative biomarkers of colorectal cancer

Cited by 145 publications

References 73 publications

Interactions between the gut microbiome and host gene regulation in cystic fibrosis

Interactions between the gut microbiome and host gene regulation in cystic fibrosis

Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

Gastric hyperplastic polyps inversely associated with current Helicobacter�pylori infection

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