Comparative Transcriptome and Microbiota Analyses Provide New Insights into the Adverse Effects of Industrial Trans Fatty Acids on the Small Intestine of C57BL/6 Mice

Purpose: To reveal the mechanism that links industrial trans fatty acids (iTFAs) to various chronic diseases, we examined the impact of iTFAs on the local microenvironment of the small intestine (duodenum, jejunum and ileum).

Methods: Forty male 8-week-old mice were fed diets containing one of the following: (1) low soybean oil (LS); (2) high soybean oil (HS); (3) low partially hydrogenated oil (LH), and (4) high partially hydrogenated oil (HH). The analysis of microbiota from small intestinal content was performed by real-time qPCR. The fatty acid composition of small intestine mucosa was measured by GC/MS, and comparative transcriptome of the small intestinal mucosa was analyzed by RNA-sequencing.

Results: The intake of iTFAs changed the fatty acid spectrum of the small intestine mucosa, especially the excessive accumulation of iTFA (mainly elaidic acid). For microbiota, the relative abundance of δ- and γ-proteobacteria, Lactobacillus, Desulfovibrio, Peptostreptococcus and Turicibacter were significantly different in the iTFA diet groups compared to the control group. Based on the identification of differently expressed genes(DEGs) and pathway annotation, comparative transcriptome analysis of the small intestine mucosa revealed obvious overexpression of genes involved in the extracellular matrix (ECM)-receptor interaction and the peroxisome proliferator-activated receptor signaling pathway, which suggests that ECM remodeling and abnormal lipid metabolism may have occurred with iTFA ingestion.

Conclusion: Our research demonstrated multiple adverse effects of iTFA that may have originated from the small intestine. This finding could be to facilitate the development of new strategies to suppress iTFA-related diseases by reversing the adverse effects of iTFA on intestinal health.