Identifying Gut Microbiota Associated With Colorectal Cancer Using a Zero-Inflated Lognormal Model

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide. Its incidence is still increasing, and the mortality rate is high. New therapeutic and prognostic strategies are urgently needed. It became increasingly recognized that the gut microbiota composition differs significantly between healthy people and CRC patients. Thus, identifying the difference between gut microbiota of the healthy people and CRC patients is fundamental to understand these microbes' functional roles in the development of CRC. We studied the microbial community structure of a CRC metagenomic dataset of 156 patients and healthy controls, and analyzed the diversity, differentially abundant bacteria, and co-occurrence networks. We applied a modified zero-inflated lognormal (ZIL) model for estimating the relative abundance. We found that the abundance of genera: Anaerostipes, Bilophila, Catenibacterium, Coprococcus, Desulfovibrio, Flavonifractor, Porphyromonas, Pseudoflavonifractor, and Weissella was significantly different between the healthy and CRC groups. We also found that bacteria such as Streptococcus, Parvimonas, Collinsella, and Citrobacter were uniquely co-occurring within the CRC patients. In addition, we found that the microbial diversity of healthy controls is significantly higher than that of the CRC patients, which indicated a significant negative correlation between gut microbiota diversity and the stage of CRC. Collectively, our results strengthened the view that individual microbes as well as the overall structure of gut microbiota were co-evolving with CRC.

Keywords: association network; colorectal cancer; gut microbiota; microbial diversity; zero-inflated lognormal model.

Figure 1

Analysis of intestinal microbial diversity in different environments. The three colors in the figure indicate the microbial diversity in different states: green represents the healthy samples, yellow represents adenoma (precancerous lesion) growth in the intestine, and red represents a sample of colorectal cancer patients. The average value of Alpha diversity of healthy samples was 4.0456, whereas the counterpart in the adenoma sample was 3.8957, and that in the cancer sample was 3.7161.

Figure 2

Differences in intestinal microbiome at the genus and species level among samples of different states. Green represents a healthy sample, and red represents a colorectal cancer sample. (A) The top nine microbial genera with significant differences in abundance. (B) The top five microbial strains with significant differences in abundance.

Figure 3

The association network of intestinal microbiome in different states. Each circle represents the average relative abundance of a microbial species in that state. The higher the average relative abundance, the larger the area of the circle. The solid gray line between the circles indicates a positive Spearman correlation between the two groups, and the solid red line indicates a negative Spearman correlation between the two groups. (A–D) The association network of intestinal microbiome in healthy, small adenoma, large adenoma and cancer samples.