Gut Bacteria Affect Colorectal Cancer Risk

The gut microbiome of patients with colorectal cancer (CRC) was less diverse than that of matched patients without cancer, and the presence of some taxa was associated with increased CRC risk, according to research published online December 6 in the Journal of the National Cancer Institute.

"Because of the potentially modifiable nature of the gut bacteria, our findings may have implications for CRC prevention," write Jiyoung Ahn, PhD, assistant professor of population health and a member of the NYU Cancer Institute, New York University School of Medicine, New York City, and colleagues.

The results came from an analysis of fecal bacterial DNA from 47 patients with CRC and 94 control participants matched to the CRC group by sex and body mass index. The investigators amplified 794,217 16S rRNA genes and then classified the sequences taxonomically.

They note that this is the first study to compare the gut microbiomes of people with and without CRC that included multiple comparisons of bacteria while controlling for possible confounders.

The researchers found decreased microbiome community diversity in patients with CRC , compared with that of healthy participants(P= .02). In an analysis by taxa, patients with CRC had lower relative abundances of Clostridia, at 68.6% compared with 77.8% in people without CRC. In contrast, patients with CRC carried a higher relative abundance of Fusobacterium (31.9% vs 11.7% for control patients).

A higher relative abundance of Fusobacterium was associated with increased CRC risk (multivariable odds ratio [OR], 4.11; 95% confidence interval [CI], 1.62 - 10.47), after adjusting for age, sex, body mass index, race, smoking, and sequencing batch.

Actinobacteria Atopobium (OR, 14.36; 95% CI, 2.78 - 74.30; P < .001) and the Bacteriodetes Porphyromonas(OR, 5.17; 95% CI, 1.75 - 15.25; P = .001) were also associated with CRC risk. The Gram-positiveAtopobium is associated with Crohn's disease and is reported to inhibit colon cancer apoptosis in vitro.Polyphyromonas, which is often found in the mouth and gastrointestinal tract, is associated with periodontal disease.

Patients with CRC tended to have more Bacteroidetes phylum bacteria (16.2% relative abundance vs 9.9% for control participants) and fewer Firmicutes (74.0% for patients with CRC compared with 80.3% for control participants). The depletion of Firmicutes was highest for the class Clostridia (68.6% for patients with CRC vs 77.8% for control participants; P = .005; false discovery rate–adjusted P < .05). Among the depleted taxa was Coprococcus in the Clostridia family Lachnospiracea. Coprococcus is responsible for the efficient fermentation of dietary fiber and other complex carbohydrates into butyrate, a major colonic metabolite that may inhibit colonic inflammation and carcinogenesis, the authors write.

In an additional assay using quantitative polymerase chain reaction for Porphyromonas and Fusobacterium, the association between CRC and these taxa remained significant. In that study, the OR for CRC with the presence of Porphyromonas was 1.44 (P = .05), and the OR for CRC with the presence of Fusobacteriumwas 1.44 (P = 0.01).