Colorectal cancer alters gut microbiome

Patients with colorectal cancer (CRC) have a substantially altered gut microbiome, characterized by changes in bacterial composition, according to a recent Singapore study. Of note, these alterations persist even after surgery.

“The variations in gut microbiota of pre- and postoperation patients may suggest possible field change in the ‘nondiseased’ colon that predisposed them to CRC in the first place due to the findings of persistent microbial dysbiosis after surgery,” the researchers said. “This study provides insights to alterations in the gut microbiota of postoperative CRC patients.”

Microbial composition was assessed in 49 faecal samples collected from 12 CRC patients (mean age 63.8 years, 58.3 percent men) and 25 noncancer controls (mean age 61.6 years, 56.0 percent men), before and 6 months after surgery, using 16S rRNA gene sequencing analysis. A total of 2,559,498 filtered sequences were obtained and used to assess species diversity and richness.

Global microbial alpha diversity was significantly lower in postoperative CRC patients, while beta-diversity analysis confirmed that there was clear segregation between CRC patients and noncancer controls. In addition, microbial composition analysis found that postoperative CRC patients had a more scattered gut microbiota, further confirming that microbial composition was significantly altered in this patient population as opposed to preoperative patients and controls. [Sci Rep 2022;12:9829]

Overall, data suggested that faecal bacterial species richness and diversity were significantly compromised in CRC patients.

In terms of specific taxonomic groups, the researchers found that the Actinobacteria and Firmicutes phyla were enriched in postoperative CRC patients, while some Bacteroidetes groups were reduced, relative to preoperative comparators.

In particular, precarcinogenic bacteria like Bacteroides fragilis and Odoribacter splanchnicus were elevated in preoperative CRC patients, though levels normalized after surgery. However, bacterial taxa associated with CRC progression remained elevated in the postoperative CRC group, indicating that dysbiosis persists even after curative resection. Meanwhile, probiotic bacteria also seemed more abundant after CRC surgery.

Such alterations in gut microbiome composition led to pathway differences. Postoperative CRC patients showed enrichment in bacteria involved in glutathione and glucose/mannose transport, among other pathways. In contrast, some metabolic pathways appeared suppressed in this patient group.

Moreover, “the inability to metabolize sulfate in the colonic environment was found to be significantly suppressed in preoperative CRC patients compared to noncancer controls” the researchers said. “In addition, correlation between increased pathogenic bacteria and infectious disease-associated pathways may be indicative of adverse postsurgery response.”

“Future studies should involve a larger sample size with shotgun microbiome sequencing data collected at multiple time points after surgery to examine if these dysbiotic patterns truly persist and also correlate with disease outcomes,” the researchers said.