Mechanism of intestinal microbiota disturbance promoting the occurrence and development of esophageal squamous cell carcinoma--based on microbiomics and metabolomics.

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is a high-risk malignant tumor that has been reported in China. Some studies indicate that gut microbiota disorders can affect the occurrence and development of ESCC, but the underlying mechanism remains unclear. In this study, we aimed to explore the possible underlying mechanisms using microbiomics and metabolomics. Fifty ESCC patients and fifty healthy controls were selected as the study subjects according to sex and age, and fecal samples were collected. 16S rDNA sequencing and LC‒MS were used for microbiomics and nontargeted metabolomics analyses. We found significant differences in the composition of the gut microbiota and metabolites between the ESCC patients and control individuals (P < 0.05). ESCC patients exhibited increased abundances of Fusobacteriaceae and Lactobacillus, increased levels of GibberellinA34 and decreased levels of 12-hydroxydodecanoic acid; these metabolites could be diagnostic and predictive markers of ESCC. An increase in the abundance of Enterobacteriaceae and Lactobacillus significantly reduced the content of L-aspartate and pantothenic acid, which may be involved in the occurrence and development of ESCC by downregulating the expression of proteins in the pantothenate and coenzyme A biosynthesis pathways. An imbalance in the intestinal flora may decrease the number of eosinophils in peripheral blood, resulting in the activation of an inflammatory response and immune dysfunction, leading to ESCC deterioration. We hypothesize that this imbalance in the gut microbiota can cause an imbalance in intestinal metabolites, which can activate carcinogenic metabolic pathways, affect inflammation and immune function, and play a role in the occurrence and development of ESCC.