Silamikele, L. | bioRxiv Science

bioRxiv2025

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

BackgroundColorectal cancer (CRC) is among the most common malignancies worldwide, with colorectal adenomas recognized as well-established precursors to CRC. Changes in gut microbiota appear to be linked to CRC by promoting chronic inflammation, immune dysfunction, and metabolic issues that drive tumor growth and progression. ObjectivesTo explore the relationship between gut microbiome composition and the presence of colorectal adenomas in patients undergoing routine colonoscopy. Materials and methodsPatients were selected from those receiving standard colonoscopy based on strict inclusion and exclusion criteria, to minimize potential confounding factors such as previous colorectal surgeries, inflammatory bowel diseases, and the use of antibiotics or probiotics. Fecal samples were collected before bowel preparation for the colonoscopy procedure, and metagenomic shotgun sequencing was used to analyze the composition and functions of the gut microbiome. ResultsOverall, 136 participants were recruited, and 56 of them had colorectal adenomas. Although no distinction was observed in alpha diversity, beta diversity analysis indicated significant differences between the adenoma-positive and adenoma-negative groups. Signs of dysbiosis were found in patients with adenomas: increased abundance of the genera Bacteroides and Prevotella and decreased abundance of Faecalibacterium and Anaerostipes species. Beta diversity analysis showed statistically significant differences in the structure of the microbiota. Significant differences in the relative abundance of UBA7597 sp003448195 were observed between groups. Functionally, decreased vitamin K2, SCFA (propionate) synthesis, along with lower Stickland fermentation activity was observed, indicating altered microbial metabolism. These changes may compromise epithelial barrier support, anti-inflammatory signaling, and energy metabolism in the colon. ConclusionsThe discovery of microbial taxa and functional pathways associated with the presence of adenomas underscores the potential of microbiota-based biomarkers and therapeutic strategies in the prevention and management of colorectal cancer.

bioinformatics↗

bioRxiv2020

Metformin strongly affects gut microbiome composition in high-fat diet-induced type 2 diabetes mouse model of both sexes

Effects of metformin, the first-line drug for type 2 diabetes therapy, on gut microbiome composition in type 2 diabetes have been described in various studies both in human subjects and animals. However, the details of the molecular mechanisms of metformin action have not been fully understood. Moreover, there is a significant lack of information on how metformin affects gut microbiome composition in female mice models, as most of the existing studies have focused on males only. Our study aimed to examine metformin-induced alterations in gut microbiome diversity and composition of high-fat diet-induced type 2 diabetes mouse model, employing a randomized block, factorial study design, and including 24 experimental units allocated to 8 treatment groups. We performed shotgun metagenomic sequencing using DNA obtained from fecal samples representing gut microbiome before and after ten weeks-long metformin treatment. We identified 100 metformin-related differentially abundant species in high-fat diet-fed mice before and after the treatment, with most of the species abundances increased. In contrast, no significant changes were observed in control diet-fed mice.We also observed sex-specific differences in response to metformin treatment. Males experienced more pronounced changes in metabolic markers, while, in females, the extent of changes in gut microbiome representatives was more marked, indicated by 53 differentially abundant species with more remarkable Log fold changes compared to the combined-sex analysis. Our results suggest that both sexes of animals should be included in future studies focusing on metformin effects on the gut microbiome.

microbiology↗