Flaxseed oil ameliorates alcoholic liver disease via anti-inflammation and modulating gut microbiota in mice.

ABSTRACT:

BACKGROUND:  Alcoholic liver disease (ALD) represents a chronic wide-spectrum of liver injury caused by consistently excessive alcohol intake. Few satisfactory advances have been made in management of ALD. Thus, novel and more practical treatment options are urgently needed. Flaxseed oil (FO) is rich in α-linolenic acid (ALA), a plant-derived n-3 polyunsaturated fatty acids (PUFAs). However, the impact of dietary FO on chronic alcohol consumption remains unknown. METHODS:  In this study, we assessed possible effects of dietary FO on attenuation of ALD and associated mechanisms in mice. Firstly, mice were randomly allocated into four groups: pair-fed (PF) with corn oil (CO) group (PF/CO); alcohol-fed (AF) with CO group (AF/CO); PF with FO group (PF/FO); AF with FO group (AF/FO). Each group was fed modified Lieber-DeCarli liquid diets containing isocaloric maltose dextrin a control or alcohol with corn oil and flaxseed oil, respectively. After 6 weeks feeding, mice were euthanized and associated indications were investigated. RESULTS:  Body weight (BW) was significantly elevated in AF/FO group compared with AF/CO group. Dietary FO reduced the abnormal elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in chronic ethanol consumption. Amelioration of these parameters as well as liver injury via HE staining in dietary FO supplementation in ALD demonstrated that dietary FO can effectively benefit for the protection against ALD. To further understand the underlying mechanisms, we investigated the inflammatory cytokine levels and gut microbiota. A series of inflammatory cytokines, including TNF-α, IL-1β, IL-6 and IL-10, were determined. As a result, TNF-α, IL-1β and IL-6 were decreased in AF/FO group compared with control group; IL-10 showed no significant alteration between AF/CO and AF/FO groups (p > 0.05). Sequencing and analysis of gut microbiota gene indicated that a reduction of Porphyromonadaceae and Parasutterella, as well as an increase in Firmicutes and Parabacteroides, were seen in AF group compared with PF control. Furthermore, dietary FO in ethanol consumption group induced a significant reduction in Proteobacteria and Porphyromonadaceae compared with AF/CO group. CONCLUSION:  Dietary FO ameliorates alcoholic liver disease via anti-inflammation and modulating gut microbiota, thus can potentially serve as an inexpensive interventions for the prevention and treatment of ALD.