Abstract
Recent studies have suggested an association between certain members of the Fusobacterium genus, especially F. nucleatum, and the progression of advanced colorectal carcinoma (CRC). We assessed such an association of the gut microbiota in Japanese patients with colorectal adenoma (CRA) or intramucosal CRC using colonoscopy aspirates. We analyzed samples from 81 Japanese patients, including 47 CRA and 24 intramucosal CRC patients, and 10 healthy subjects. Metagenomic analysis of the V3-V4 region of the 16S ribosomal RNA gene was performed. The linear discriminant analysis (LDA) effect size (LEfSe) method was used to examine microbial dysbiosis, revealing significant differences in bacterial abundances between the healthy controls and CRA or intramucosal CRC patients. In particular, F. varium was statistically more abundant in patients with CRA and intramucosal CRC than in healthy subjects. Here, we present the metagenomic profile of CRA and intramucosal CRC and demonstrate that F. varium is at least partially involved in the pathogenesis of CRA and intramucosal CRC.
Highlights
Increasing evidence suggests that the human gut microbiota contributes to chronic inflammation and plays important roles in the early stage of carcinogenesis of colorectal adenocarcinoma (CRC) and colorectal adenoma (CRA) through interference with various intestinal functions [1, 2]
Weighted UniFrac PCoA indicated that no distinct aggregation was observed between CRA and intramucosal CRC patients, whereas healthy subjects were found to be aggregated on the lower side (Fig 1A), suggesting a difference in gut microbiota composition between these patients and healthy subjects
The present study has demonstrated for the first time that F. varium may be associated with the development of CRA as well as intramucosal CRC, as analyzed by a metagenomic approach using next-generation sequencing (NGS)
Summary
Increasing evidence suggests that the human gut microbiota contributes to chronic inflammation and plays important roles in the early stage of carcinogenesis of colorectal adenocarcinoma (CRC) and colorectal adenoma (CRA) through interference with various intestinal functions [1, 2]. Chronic inflammation induced by the microbiota is associated with altered interactions between the host and the microbiota, microbial imbalance (dysbiosis), and infections with specific pathogens in patients with CRC or CRA [3]. Studies recently suggested that Fusobacterium spp. overall (Pan-fusobacterium), especially Fusobacterium nucleatum (F. nucleatum), are abundant in advanced CRC tissue and may contribute to invasion and metastatic proliferation [4,5,6]. F. nucleatum in advanced CRC is associated with CpG island. Fusobacterium varium in colorectal adenoma data collection and analysis, decision to publish, or preparation of the manuscript
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