Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis

Abstract

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors primarily affecting individuals over the age of 50 years. Recent studies have suggested that the dysbiosis of the gut microbiota, a community of microorganisms in the human gut, is closely associated with the occurrence and development of CRC. Additionally, inflammatory factors (IFs) have also been reported to play a significant role in the development of CRC. However, the causal relationships between the gut microbiota, IFs, and CRC remain unclear.MethodsIn this study, we performed Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data to explore the causal relationship between the gut microbiota, IFs, and CRC. The gut microbiota GWAS data were obtained from the MiBioGen study, while the IFs GWAS data were derived from the comprehensive analysis of three independent cohorts. Causal relationship analysis was conducted using appropriate instrumental variables (IVs) and statistical models.ResultsMR analysis of the gut microbiota and CRC revealed a negative correlation between the Lachnospiraceae species in the gut and CRC risk, while a positive correlation was observed between Porphyromonadaceae species, Lachnospiraceae UCG010 genus, Lachnospira genus, and Sellimonas genus in the gut, and CRC risk. Additionally, we observed a causal relationship between IL-10 and CRC risk. These findings suggest that the dysbiosis of the gut microbiota might be associated with an increased risk of CRC and that specific bacterial groups may play a crucial role in the occurrence and development of CRC.ConclusionUsing MR analysis, this study revealed the causal relationships between the gut microbiota, IFs, and CRC. The negative correlation between the Lachnospiraceae species in the gut and CRC risk, as well as the causal relationship between IL-10 and CRC, provide important clues for the potential roles of gut microbiota regulation and inflammatory factor control in the prevention and treatment of CRC.

Colorectal Cancer: Epidemiology, Risk Factors, and Prevention

“…Their findings suggested causal relationships between the intestinal microbiome and the risk of CRC. The results of this study revealed that dysbiosis of the intestinal microbiota may play an important role in development of CRC, suggesting their potential implications in CRC prevention [141]. Microbiome modulation was proposed as a new strategy for the prevention or treatment of CRC [136].…”

“…Recent studies provide evidence on CRC-related species of the gut microbiota [139,140]. Ma et al performed a Mendelian randomization analysis to assess the relationship between gut microbiota and CRC [141]. They found a negative correlation between the Lachnospiraceae species and CRC risk, while the Porphyromonadaceae species, Lachnospiraceae UCG010 genus, Lachnospira genus, and Sellimonas genus had a positive relationship with the risk of CRC.…”