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Abstract |
Conservative estimates are that around 20% of all malignancies may be attributed to microbiota. Especially in the gastrointestinal (GI) tract, infection can cause chronic inflammation and further influence immune response to create a proinflammatory microenvironment for cancer development. This can account in part for the reason that the immunotherapy in colon cancer is less efficacious than in non-GI tract cancers. We proposed a systematic computational study to profile the microbiome from next generation sequencing of gastric biopsy samples, and evaluate the relationships among microbiome composition, host immune response and genomic characterization.
In total, 27 endoscopic biopsies from 3 locations in the gastric antrum/body were freshly frozen for whole genome sequencing and transcriptome analysis. In addition, TCGA whole genome sequencing (WGS) data were also analyzed for microbiome composition.
H. pylori was detected in all positive infection gastric biopsy samples by our pipeline, and the results were successfully validated by qPCR. Comparing to other traditional bacterial identification methods, our pipeline shows a strong capacity for profiling microbiome from low bacterial content biopsy samples. We observed a high positive correlation between the H. pylori content and total non-H. pylori bacteria content. And we also identified significantly differentially expressed immune-related genes between active H. pylori infection and negative samples. Finally, we analyzed collected TCGA WGS data, and identified the dominant species from the different cancer studies, such as Bacteroides fragilis in rectum adenocarcinoma, and Fusobacterium nucleatum in colon adenocarcinoma. The correlation among microbiome composition, the expression of immune-related genes and cancer genomic characterization were also demonstrated in this study. |
