Abstract: This study aimed to investigate the effect of linoleic acid and α-linolenic acid mixtures on acute liver injury and the intestinal microflora diversity in mice. In total 80 specific pathogen free (SPF) Kunming mice were divided into eight groups: normal, CCl4-induced model, positive control, and linoleic acid/α-linolenic acid mixtures at ratios of 4:1, 2:1, 1:1, 1:2 and 1:4. Serum immune functions and intestinal microflora structure in each group of mice were determined. The results showed that linoleic acid and α-linolenic acid mixtures could significantly reduce the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.05), decreased liver and spleen indices (P > 0.05), and decreased the content of malondialdehyde (MDA) as well as the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver cells (P < 0.05) compared with CCl4-induced model . These changes were consistent with the results of liver histopathological observation. High throughput sequencing results showed that the diversity of intestinal microflora in the model group dropped significantly compared with normal group (P < 0.05), while the diversity and abundance of intestinal microflora significantly increased after intervention with the 2:1 mixture of linoleic acid/α-linolenic acid compared with the CCl4 model group (P < 0.05), and its structure also changed. Moreover, the most prominent hepatoprotective effect was observed with the 2:1 mixture of linoleic acid and α-linolenic acid, which was basically consistent with that of silybin as a positive control. These results not only confirm the hepatoprotective effect of linoleic acid/α-linolenic acid mixtures, but also provide a theoretical basis for the scientific intake of linoleic acid/α-linolenic acid mixtures and serve as a guide for future development and application of hepatoprotective agents.

Key words: α-linolenic acid; linoleic acid; acute liver injury; liver protection; intestinal flora