Systematic Review: The Relationship Between the Faecal Microbiome and Colorectal Neoplasia in Shotgun Metagenomic Studies.

Background: The human gut microbiome is of academic and clinical interest. Associations between certain organisms and colorectal neoplasia have been reported, but findings have limited reproducibility in different populations.

Methods: We performed a systematic review of whole metagenome shotgun sequencing studies using faecal samples from patients with colorectal neoplasia and control populations. Searches were performed on 30th June 2023. We identified 26 studies, reporting on 22 study populations (13 from Asia, five from Europe and four from North America). Study size ranged from 14 to 971 individuals (mean 170).

Results: Some reproducible data were identified, such as the significant enrichment of Fusobacterium nucleatum and Parvimonas micra in colorectal cancer patients compared to controls (in 10 and nine studies, respectively). However, 21 out of 26 studies scored poorly on quality appraisal, specifically surrounding selection of cases and controls. Definitions of controls varied; some studies used individuals with normal endoscopic investigations, some used 'healthy' individuals where no colonoscopy was performed, and one used those with non-neoplastic findings (haemorrhoids). There was even less reproducibility of data in studies where individuals with colorectal polyps were compared to controls, possibly because of heterogeneity in these patient groupings as a variety of definitions for 'polyp cases' were used.

Conclusions: Heterogeneity and potential for bias indicates that findings should be interpreted with caution. Standardised protocols to ensure robust methodology and allow pooling of large-scale data are required before these findings can be used in clinical practice (PROSPERO: CRD42023431977).