Gut Microbiome

Colorectal adenoma presence is associated with decreased menaquinone pathway functions in the gut microbiome of patients undergoing routine colonoscopy.

TL;DR

The presence of colorectal adenomas was associated with reduced microbial metabolic functions linked to vitamin K₂ biosynthesis, amino acid fermentation, and propionate production, alongside compositional shifts toward a less functionally robust gut microbiome.

Key Findings

Alpha diversity did not differ significantly between adenoma-positive and adenoma-negative groups.

  • 136 participants were included in total, of whom 56 had colorectal adenomas.
  • Alpha diversity indices (presumably richness and evenness metrics) were comparable between the two groups.
  • This cross-sectional case-control study used shotgun metagenomic sequencing on fecal samples collected prior to bowel preparation.
  • Strict inclusion and exclusion criteria were applied to minimize confounding factors such as inflammatory bowel disease, prior colorectal surgery, and recent antibiotic or probiotic use.

Beta diversity analysis revealed significant differences in overall microbial community structure between adenoma-positive and adenoma-negative patients.

  • Despite no alpha diversity differences, beta diversity (community-level composition) was significantly different between groups.
  • The study used shotgun metagenomic sequencing to assess taxonomic composition.
  • 136 participants total (56 adenoma-positive, 80 adenoma-negative) were analyzed.

Adenoma-positive patients showed descriptive genus-level differences consistent with dysbiosis, including higher relative abundance of Bacteroides and Prevotella and lower abundance of Faecalibacterium and Anaerostipes.

  • Higher relative abundance of Bacteroides and Prevotella was observed in the adenoma group.
  • Lower abundance of Faecalibacterium and Anaerostipes was noted in adenoma-positive patients.
  • These genus-level differences were described as 'features of dysbiosis' in adenoma-positive patients.
  • These findings were described as 'descriptive' rather than reaching formal statistical significance thresholds in differential abundance analysis.

Differential abundance analysis identified a single species-level feature, UBA7597 sp003448195, as enriched in the adenoma group.

  • UBA7597 sp003448195 was the only species-level feature identified as enriched in adenoma-positive patients through formal differential abundance analysis.
  • Shotgun metagenomic sequencing enabled species-level taxonomic resolution.
  • 56 adenoma-positive and 80 adenoma-negative participants were compared.

Functional profiling revealed reduced microbial pathways related to menaquinone (vitamin K₂) biosynthesis in patients with colorectal adenomas.

  • Menaquinone biosynthesis pathways were among the most prominent functionally reduced pathways in the adenoma group.
  • Functional pathways were assessed using shotgun metagenomic sequencing and functional profiling methods.
  • The reduction in menaquinone pathway functions is highlighted in the paper's title as the primary finding.
  • These functional differences were identified despite the absence of significant alpha diversity differences between groups.

Stickland fermentation pathways were reduced in the gut microbiome of adenoma-positive patients.

  • Stickland fermentation, an amino acid fermentation pathway carried out by certain anaerobic bacteria, was among the functionally reduced pathways in the adenoma group.
  • This finding was identified through functional profiling of shotgun metagenomic sequencing data.
  • Reduced Stickland fermentation was interpreted as part of broader functional microbiome alterations associated with early colorectal neoplasia.

Short-chain fatty acid (propionate) production pathways were reduced in the gut microbiome of patients with colorectal adenomas.

  • Propionate production pathways were identified as reduced in adenoma-positive compared to adenoma-negative patients.
  • Reduced propionate production was consistent with lower abundance of Faecalibacterium and Anaerostipes, which are known propionate and butyrate producers.
  • These functional changes were interpreted as potentially impacting epithelial and immune homeostasis in the colonic microenvironment.

Early colorectal neoplasia is accompanied by functional microbiome alterations that may serve as markers of adenoma-associated dysbiosis and provide insight into early metabolic changes in the colonic microenvironment.

  • The study found that functional pathway differences were detectable at the adenoma (precancerous) stage, prior to frank malignancy.
  • The authors suggest these functional alterations may reflect 'loss of microbial metabolic functions supporting epithelial and immune homeostasis.'
  • Findings were derived from a cross-sectional case-control design, limiting causal inference.
  • The authors propose these functional markers could serve as early indicators of adenoma-associated dysbiosis.

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Citation

Vilkoite I, Silamiķelis I, Kloviņš J, Tolmanis I, Lejnieks A, Runce E, et al.. (2026). Colorectal adenoma presence is associated with decreased menaquinone pathway functions in the gut microbiome of patients undergoing routine colonoscopy.. PloS one. https://doi.org/10.1371/journal.pone.0344050