Background <p>Identification of reliable biomarkers in Hepato-pancreatico-biliary (HPBC) and gastric cancers (GC) has been extremely challenging, and no effective screening modality is currently available. There is an increasing appreciation that the gut microbiome may be altered in these diseases and act as a predictor of disease or disease outcome.</p> Aim <p>To examine the gut microbiota in a cohort of treatment naïve, newly diagnosed pancreatic, biliary and gastric cancer patients and age matched controls.</p> Methods <p>Stool samples from 37 treatment naïve, newly diagnosed HPBC and GC patients and 47 age-matched non-cancer controls were prospectively collected. Microbiota composition was determined by 16&#xa0;S rRNA amplicon sequencing. Differences in the microbial composition of HC and HPBC patients were assessed using linear discriminant analysis effect size. Predictive functional profiling of microbial communities was obtained with PICRUSt.</p> Results <p>The gut microbiota of HPBC patients was significantly different compared to the non-cancer controls. <i>Enterococcus</i>,<i> Enterobacter</i>,<i> Streptococcus and Lactobacillus</i>, were significantly increased in HPBC, while numerous <i>Lachnospiraceae</i>,<i> Ruminococcaceae_UCG014</i>,<i> Bacteroides</i> and <i>Faecalibacterium</i> were significantly reduced in HPBC. <i>Enterobacter</i> and <i>Enterococcus</i> best discriminated the HPBC samples, while <i>Butyrivibrio</i> and <i>Lachnospira</i> best discriminated the non-cancer controls. There was a trend towards decreased diversity and richness in cancer patients with increasing severity of cancer stage.</p> Discussion <p>We report a significant difference in microbial composition in patients with pancreatic and biliary cancer compared to non-cancer controls, which is associated with an increase in pathogens and a decrease in potential beneficial bacteria. Our results support the potential for the gut microbiota to act as an early biomarker for these highly fatal and poorly diagnosed gastrointestinal cancers.</p>

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The gut microbiota of hepato-pancreatico-biliary and gastric cancer patients is altered in composition and functionality

  • Louise Daly,
  • Erin Stella Sullivan,
  • Fiona Fouhy,
  • Claire Watkins,
  • Daniel Linaries,
  • Derek Power,
  • Criostoir O’Suilleabhain,
  • Adrian O’Sullivan,
  • Paul O’Toole,
  • Paul Ross,
  • Catherine Stanton,
  • Aoife Ryan

摘要

Background

Identification of reliable biomarkers in Hepato-pancreatico-biliary (HPBC) and gastric cancers (GC) has been extremely challenging, and no effective screening modality is currently available. There is an increasing appreciation that the gut microbiome may be altered in these diseases and act as a predictor of disease or disease outcome.

Aim

To examine the gut microbiota in a cohort of treatment naïve, newly diagnosed pancreatic, biliary and gastric cancer patients and age matched controls.

Methods

Stool samples from 37 treatment naïve, newly diagnosed HPBC and GC patients and 47 age-matched non-cancer controls were prospectively collected. Microbiota composition was determined by 16 S rRNA amplicon sequencing. Differences in the microbial composition of HC and HPBC patients were assessed using linear discriminant analysis effect size. Predictive functional profiling of microbial communities was obtained with PICRUSt.

Results

The gut microbiota of HPBC patients was significantly different compared to the non-cancer controls. Enterococcus, Enterobacter, Streptococcus and Lactobacillus, were significantly increased in HPBC, while numerous Lachnospiraceae, Ruminococcaceae_UCG014, Bacteroides and Faecalibacterium were significantly reduced in HPBC. Enterobacter and Enterococcus best discriminated the HPBC samples, while Butyrivibrio and Lachnospira best discriminated the non-cancer controls. There was a trend towards decreased diversity and richness in cancer patients with increasing severity of cancer stage.

Discussion

We report a significant difference in microbial composition in patients with pancreatic and biliary cancer compared to non-cancer controls, which is associated with an increase in pathogens and a decrease in potential beneficial bacteria. Our results support the potential for the gut microbiota to act as an early biomarker for these highly fatal and poorly diagnosed gastrointestinal cancers.