Shifts in the Fecal Microbiota Associated with Adenomatous Polyps

Abstract

Background: Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas.

Methods: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547).

Results: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism.

Conclusions: These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio In turn, these microbes may produce genotoxic or inflammatory metabolites such as H₂S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer.

Impact: This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota. Cancer Epidemiol Biomarkers Prev; 26(1); 85-94. ©2016 AACR.

Figure 1

Subject enrollment flowchart.

Figure 2

Thirty-one taxa differ in abundance between patients with and without adenomas. A) Relative abundance of OTUs in each group, across taxonomic levels. B) −log(P value) of these taxa’s differential abundance. C) Cladogram of the taxa that differed between groups.

Figure 3

Based on the results of a random forests (RF) algorithm, four taxa significantly predict adenomatous polyp status: Streptococcus, Veillonella, Mogibacterium, and Sutterella. The four taxa that are significant predictors are shown in green. Blue boxplots correspond to minimal, average and maximum Z score of a shadow taxa. Red, yellow and green boxplots represent Z scores of rejected, tentative and confirmed taxa respectively.

Figure 4

Functional differences, predicted using 16S sequencing data, between the gut microbial communities of patients with and without adenomas, A) Pink bars represent the −log(P value) of KEGG metabolic pathways predicted to be more common among the microbiota of individuals with adenomatous polyps. Turquoise bars represent the effect sizes of functions predicted to be more common among the microbiota of individuals without polyps. B) Summary of the log(P value) of COG groups predicted to differ between the groups; colors as in (A).