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

**Authors:** Ilona Vilkoite, Ivars Silamiķelis, Jānis Kloviņš, Ivars Tolmanis, Aivars Lejnieks, Elīna Runce, Krista Cēbere, Ksenija Margole, Olga Sjomina, Laila Silamiķele, Jad El Masri, Jad El Masri, Jad El Masri

PMC · DOI: 10.1371/journal.pone.0344050 · 2026-03-11

## TL;DR

This study finds that gut microbes in people with colorectal adenomas show reduced functions related to vitamin K₂ and other key metabolic processes, suggesting early signs of gut dysbiosis linked to cancer risk.

## Contribution

The study identifies specific functional microbiome changes associated with early colorectal adenomas, highlighting potential biomarkers for dysbiosis and cancer prevention.

## Key findings

- Adenoma presence correlates with reduced gut microbial functions for menaquinone (vitamin K₂) biosynthesis and propionate production.
- Adenoma-positive patients show increased Bacteroides and Prevotella and decreased Faecalibacterium and Anaerostipes at the genus level.
- A single species-level feature, UBA7597 sp003448195, is enriched in the adenoma group.

## Abstract

Colorectal adenomas are key precancerous lesions and a major target for colorectal cancer prevention. While gut microbiome alterations are well described in colorectal cancer, microbial composition and functional capacity at the adenoma stage remain poorly understood. Emerging metagenomic data suggest early adenomas are associated with loss of microbial metabolic functions supporting epithelial and immune homeostasis.

To investigate the association between gut microbiome composition and functional pathways and the presence of colorectal adenomas in patients undergoing routine colonoscopy.

This cross-sectional case–control study included adult patients undergoing routine colonoscopy. Participants were enrolled based on strict inclusion and exclusion criteria to minimize confounding factors such as inflammatory bowel disease, prior colorectal surgery, and recent antibiotic or probiotic use. Fecal samples were collected prior to bowel preparation, and gut microbiome taxonomic composition and functional pathways were analyzed using shotgun metagenomic sequencing.

A total of 136 participants were included, of whom 56 had colorectal adenomas. Alpha diversity indices did not differ significantly between adenoma-positive and adenoma-negative groups. In contrast, beta diversity analysis revealed significant differences in overall microbial community structure. Descriptive genus-level differences suggested features of dysbiosis in adenoma-positive patients, including higher relative abundance of Bacteroides and Prevotella and lower abundance of Faecalibacterium and Anaerostipes. Differential abundance analysis identified a single species-level feature, UBA7597 sp003448195, enriched in the adenoma group. Functional profiling showed reduced microbial pathways related to menaquinone (vitamin K₂) biosynthesis, Stickland fermentation, and short-chain fatty acid (propionate) production in patients with adenomas.

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. These findings indicate that 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.

## Linked entities

- **Chemicals:** menaquinone (PubChem CID 14009404), propionate (PubChem CID 104745)
- **Diseases:** colorectal adenoma (MONDO:0005484), colorectal cancer (MONDO:0005575)
- **Species:** Bacteroides (taxon 816), Prevotella (taxon 838), Faecalibacterium (taxon 216851), Anaerostipes (taxon 207244)

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** bowel inflammation (MESH:D007249), dysplasia (MESH:D015792), ID (MESH:C537985), Hereditary polyposis syndrome (MESH:D009386), diverticulitis (MESH:D004238), dysbiosis (MESH:D064806), cancer (MESH:D009369), substance abuse (MESH:D019966), Chronic kidney disease (MESH:D051436), autoimmune diseases (MESH:D001327), SSL-D (MESH:D009059), obesity (MESH:D009765), colorectal polyps (MESH:D003111), Diarrhea (MESH:D003967), colorectal carcinogenesis (MESH:D063646), Adenoma (MESH:D000236), metabolic disorders (MESH:D008659), viral hepatitis B or C infections (MESH:D014777), CRC (MESH:D015179), tumorigenic (MESH:D002471), precancerous lesions (MESH:D011230), immune dysfunction (MESH:D007154), gastrointestinal diseases (MESH:D005767), Polyps (MESH:D011127), Inflammatory bowel diseases (MESH:D015212), HGD (MESH:D008228), Oncologic diseases (MESH:D000072716), HIV (MESH:D015658), chronic (MESH:D002908), SM-s (MESH:D009361), ulcerative colitis (MESH:D003093)
- **Chemicals:** pyruvate (MESH:D019289), mevalonate (MESH:D008798), oxygen (MESH:D010100), sulfate (MESH:D013431), nitrogen (MESH:D009584), menaquinone (MESH:D024482), metformin (MESH:D008687), aspirin (MESH:D001241), propofol (MESH:D015742), sulfur (MESH:D013455), bile acid (MESH:D001647), PONE-D-25-58757R1 (-), NADPH (MESH:D009249), amino acid (MESH:D000596), butyrate (MESH:D002087), carbohydrate (MESH:D002241), propanoate (MESH:D011422), alcohol (MESH:D000438), NAD (MESH:D009243), SCFA (MESH:D005232)
- **Species:** Faecalibacterium (genus) [taxon 216851], Holdemanella (genus) [taxon 1573535], Escherichia coli (E. coli, species) [taxon 562], Bacillus subtilis (species) [taxon 1423], Prevotella (genus) [taxon 838], Roseburia (genus) [taxon 841], Clostridia (class) [taxon 186801], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Bacteroides (genus) [taxon 816], Lactococcus (lactic streptococci, genus) [taxon 1357], Collinsella (genus) [taxon 102106], Bacteroides fragilis (species) [taxon 817], Alistipes (genus) [taxon 239759], Homo sapiens (human, species) [taxon 9606], Clostridium (genus) [taxon 1485], Shigella (genus) [taxon 620], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Anaerostipes (genus) [taxon 207244], Klebsiella aerogenes (species) [taxon 548], Blautia (genus) [taxon 572511], gut metagenome (species) [taxon 749906]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12978465/full.md

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Source: https://tomesphere.com/paper/PMC12978465