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Decreased ?-6:?-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury.

ABSTRACT: 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 with a concomitant reduction in liver injury.

SUBMITTER: Warner DR

PROVIDER: S-EPMC6889711 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Decreased ω-6:ω-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury.

Warner Dennis R DR Warner Jeffrey B JB Hardesty Josiah E JE Song Ying L YL King Taylor N TN Kang Jing X JX Chen Chih-Yu CY Xie Shanfu S Yuan Fang F Prodhan Md Aminul Islam MAI Ma Xipeng X Zhang Xiang X Rouchka Eric C EC Maddipati Krishna Rao KR Whitlock Joan J Li Eric C EC Wang Gary P GP McClain Craig J CJ Kirpich Irina A IA

Journal of lipid research 20191004 12

Ethanol (EtOH)-induced alterations in intestinal homeostasis lead to multi-system pathologies, including liver injury. ω-6 PUFAs exert pro-inflammatory activity, while ω-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 ω-6:ω-3 PUFA ratio would attenuate EtOH-mediated alterations in the gut-liver axis. ω-3 FA desaturase-1 (<i>fat-1</i>) mice, which endogenou ...[more]

PMID: 31586017

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Decreased ?-6:?-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury.

Publications

Decreased ω-6:ω-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury.

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