Abstract:
Objective To explore the correlation between alterations in intestinal microbiota composition and abnormal cytokine expression in patients with gastric cancer.
Methods Fecal and peripheral blood samples were collected from 81 patients with gastric cancer (gastric cancer group) and 85 healthy subjects (healthy control group). Fecal bacterial DNA was sequenced through 16S rRNA gene amplicon sequencing, and the serum levels of 17 cytokines were measured with the AimPlex multiplex assay technology: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-15, IL-17A, tumor necrosis factor (TNF)-α, TNF-β, granulocyte- macrophage colony-stimulating factor (GM-CSF), granulocyte-colony-stimulating factor (G-CSF), interferon-γ, interferon gamma-induced protein 10, macrophage chemotactic protein 1 (MCP-1), and vascular endothelial growth factor A (VEGF-A).
Results In the gastric cancer group, the abundances of 11 butyrate-producing bacteria, including certain genera of the Lachnospiraceae family (such as Lachnospira and Roseburia) and Faecalibacterium, considerably decreased. By contrast, the abundances of nine bacterial taxa, including Escherichia–Shigella, Streptococcus, Veillonella, and Parabacteroides, significantly increased. Correlation analysis showed that the decrease in the abundance of butyrate-producing bacteria were significantly negatively correlated with the high expression levels of pro-angiogenic and immunosuppressive cytokines in the gastric cancer group, including IP-10, IL-10, MCP-1, IL-8, IL-6, and VEGF-A. However, the decrease was significantly positively correlated with the downregulation of antitumor immune-related cytokines, including IL-2, IL-17A, IL-1β, TNF-β, and GM-CSF. Conversely, the enriched bacterial taxa exhibited opposite correlation patterns with these cytokines.
Conclusion A close correlation is observed between intestinal microbiota dysbiosis and abnormal cytokine expression in patients with gastric cancer. The findings suggest that restoring the intestinal microbiota through fecal microbiota transplantation is a promising strategy for regulating cytokines and is a potential research direction for the adjuvant therapy of gastric cancer.