Decreased {omega}-6:{omega}-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury [Research Articles]

Ethanol (EtOH)-induced alterations in intestinal homeostasis lead to multi-system pathologies, including liver injury. -6 PUFAs exert pro-inflammatory activity, while -3 PUFAs promote anti-inflammatory activity that is mediated, in part, through specialized pro-resolving mediators [e.g., resolvin D1 (RvD1)]. We tested the hypothesis that a decrease in the -6:-3 PUFA ratio would attenuate EtOH-mediated alterations in the gut-liver axis. -3 FA desaturase-1 (fat-1) mice, which endogenously increase -3 PUFA levels, were protected against EtOH-mediated downregulation of intestinal tight junction proteins in organoid cultures and in vivo. EtOH- and lipopolysaccharide-induced expression of INF-, Il-6, and Cxcl1 was attenuated in fat-1 and WT RvD1-treated mice. RNA-seq of ileum tissue revealed upregulation of several genes involved in cell proliferation, stem cell renewal, and antimicrobial defense (including Alpi and Leap2) in fat-1 versus WT mice fed EtOH. fat-1 mice were also resistant to EtOH-mediated downregulation of genes important for xenobiotic/bile acid detoxification. Further, gut microbiome and plasma metabolomics revealed several changes in fat-1 versus WT mice that may contribute to a reduced inflammatory response. Finally, these data correlated with a significant reduction in liver injury. Our study suggests that -3 PUFA enrichment or treatment with resolvins can attenuate the disruption in intestinal homeostasis caused by EtOH consumption and systemic inflammation wit...

Source: The Journal of Lipid Research - December 1, 2019 Category: Lipidology Authors: Warner, D. R., Warner, J. B., Hardesty, J. E., Song, Y. L., King, T. N., Kang, J. X., Chen, C.-Y., Xie, S., Yuan, F., Prodhan, M. A. I., Ma, X., Zhang, X., Rouchka, E. C., Maddipati, K. R., Whitlock, J., Li, E. C., Wang, G. P., McClain, C. J., Kirpich, I. Tags: Research Articles Source Type: research