Gut microbiota dysbiosis with increased pathogenic bacteria and decreased beneficial bacteria is associated with colorectal cancer (CRC) development. This study examined the effect of a newly developed probiotic formula in modulating CRC-related bacteria. We developed a probiotic formula containing three bifidobacteria (B. adolescentis, B. longum, and B. bifidum) based on the identification of bacterial species that showed significant correlations with CRC-related bacteria including Fusobacterium nucleatum (Fn), Lachnoclostridium sp. m3, Clostridium hathewayi (Ch), and Bacteroides clarus (Bc). We co-cultured Fn with each bifidobacterium or the combined formula and examined the growth of Fn by qPCR. The three individual bifidobacteria significantly inhibited the growth of Fn compared to the control treatment (24~65% inhibition; all p < 0.001). The combination of the three bifidobacteria showed a greater inhibitory effect on Fn growth (70% inhibition) than the individual bifidobacteria (all p < 0.05). We further examined the effect of the probiotic formula in a pilot study of 72 subjects (40 on probiotics; 32 with no intervention) for 4 weeks and followed them up for 12 weeks. The relative fecal abundances of the bifidobacteria in the formula and the CRC-related markers (Fn, m3, Ch, and Bc) were quantitated by qPCR before and after the intervention, and the combined CRC risk score (4Bac; Fn, m3, Ch, and Bc) was evaluated. Subjects with probiotics intervention showed significantly increased abundances of the bifidobacteria from week 2 to week 5 compared to baseline (p < 0.05), and the abundances dropped to baseline levels after the cessation of the intervention. There were significant decreases in the levels of CRC-related markers (Fn and m3) and the CRC risk score (4Bac) from week 2 to week 12 compared to baseline levels (p < 0.05) in the intervention group but not in the control group. A novel probiotic formula containing B. adolescentis, B. longum, and B. bifidum was effective in inhibiting the growth of F. nucleatum in vitro and improving the gut microbial environment against CRC development.

We previously developed a four-marker panel for the diagnosis of colorectal cancer (CRC) and adenoma. This study aimed to identify novel bacterial markers to improve adenoma detection using metagenomics and qPCR. Candidate markers were identified from metagenomic data (n = 492) using ANCOM-BC2 and Spearman’s rank correlation analysis and were subsequently validated in an independent cohort (n = 426). Diagnostic performance was assessed both individually and in combination with our previously identified markers and FIT. Metagenomic analysis identified 21 candidate markers that increased along the normal–adenoma–carcinoma axis. Two top candidates, Cloacibacillus porcorum (Cp) and Intestinimonas butyriciproducens, were validated via qPCR and showed significant correlations with metagenomic abundances (both p < 0.0001). ROC analysis demonstrated that Cp levels significantly distinguished CRC and adenoma from controls, whereas I. butyriciproducens distinguished only CRC. The prevalence of Cp was significantly higher in adenoma and CRC than in controls (all p < 0.05). Multivariate analysis confirmed that Cp was independently associated with CRC and adenoma diagnoses. Adding Cp to the four-marker panel improved diagnostic sensitivity from 44.8% to 58.7% for adenoma and from 85.7% to 88.6% for CRC (specificity = 85%). When further combined with FIT, Cp improved sensitivity from 47.6% to 64.3% for adenoma and from 95.2% to 96.2% for CRC (specificity = 84.6%). C. porcorum is a novel bacterial marker that may aid in the non-invasive diagnosis of colorectal adenoma.

Both gut microbiota dysbiosis and disrupted cholesterol metabolism are associated with colorectal cancer (CRC). While the interactions between these two factors have been well explored in diseases such as cardiovascular disease and atherosclerosis, their interactions and underlying mechanisms in CRC pathogenesis remain insufficiently explored, constituting a critical area for further investigation. This review examines the complex relationship between gut microbiota and cholesterol metabolism in CRC development from 2 perspectives: how specific gut microbial species can increase CRC risk by modulating cholesterol metabolism, particularly through bile acids and oxysterols, and how disrupted cholesterol metabolism can exacerbate microbial dysbiosis and promote CRC. The bidirectional relationship between gut dysbiosis and cholesterol dysregulation creates a vicious cycle that drives CRC development. Moreover, the potential of targeting the gut microbiome and cholesterol metabolism to develop new strategies for preventing and treating CRC is discussed, highlighting the promise of certain bacterial strains that exert protective effects via cholesterol-lowering mechanisms. By elucidating the intricate connections between gut microbiota, cholesterol metabolism, and CRC, this review paves the way for innovative approaches in CRC prevention and therapy.