Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease characterized with the spectrum of hepatic steatosis, inflammation, and fibrosis. The etiology of NAFLD remains incompletely understood. Numerous studies have implied that the gut microbiota (GM) is involved in the development of NAFLD, as it particularly mediating the interaction between nutrient intake and the gut–liver function. Meanwhile, the omega-3 and omega-6 polyunsaturated fatty acids (n-3/n-6 PUFA) as essential fatty acids have been linked to NAFLD. Increasing studies in the past decades have indicated that there is a reciprocal interaction between GM and n-3/n-6 PUFA, which may be underlying at least in part, the pathogenesis of NAFLD. In this review, we will discuss: (1) How GM is linked to NAFLD by interacting with various nutrients; (2) How imbalanced dietary n-3/n-6 PUFA is linked to NAFLD; (3) How n-3/n-6 PUFA may affect the GM balance, leading to altered nutrients release to the liver; and (4) How GM may modify ingested n-3/n-6 PUFA and alter their absorption, bioavailability, and biotransformation.
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Lazo M, Hernaez R, Eberhardt MS, et al. Prevalence of nonalcoholic fatty liver disease in the United States: the third National Health and Nutrition Examination Survey, 1988–1994. Am J Epidemiol. 2013;178:38–45.
Adams LA, Lymp JF, Sauver JSt, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129:113–121.
Gäbele E, Dostert K, Hofmann C, et al. DSS induced colitis increases portal LPS levels and enhances hepatic inflammation and fibrogenesis in experimental NASH. J Hepatol. 2011;55:1391–1399.
Kolodziejczyk A, Zheng D, Shibolet O, et al. The role of the microbiome in NAFLD and NASH. Mol Med. 2019;11:e9302.
Hoyles L, Fernández-Real J-M, Federici M, et al. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nat. Med. 2018;24:1070–1080.
Gaggini M, Carli F, Rosso C, et al. Altered amino acid concentrations in NAFLD: impact of obesity and insulin resistance. Hepatology. 2018;67:8.
Krebs M, Krssak M, Bernroider E, et al. Mechanism of amino acid-induced skeletal muscle insulin resistance in humans. Diabetes. 2002;51:600–605.
Hondaa T, Ishigamia M, Ishigami M, et al. Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice. Metab Clin Exp. 2017;69:177–187.
Patterson E, Wall R, Fitzgerald F, et al. Health implications of high dietary omega-6 polyunsaturated fatty acids. J Nutr Metab. 2012;2012:1–16.
Lee JY, Plakidas A, Lee WH, et al. Differential modulation of toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res. 2003;44:479–486.
Gupta G, Khadema F, Uzonnaab JE, et al. Role of hepatic stellate cell (HSC)-derived cytokines in hepatic inflammation and immunity. Cytokines. 2019;24:154542.
Ibrahim A, Mbodji K, Hassan A, et al. Anti-inflammatory and anti-angiogenic effect of long chain n-3 polyunsaturated fatty acids in intestinal microvascular endothelium. Clin Nutr. 2011;30:678–687.
Allam-Ndoul B, Guénard F, Barbier O, et al. Effect of n-3 fatty acids on the expression of inflammatory genes in THP-1 macrophages. Lipids Health Dis. 2016;15:69.
Prossomariti A, Scaioli E, Piazzi G, et al. Short-term treatment with eicosapentaenoic acid improves inflammation and affects colonic differentiation markers and microbiota in patients with ulcerative colitis. Sci Rep. 2017;7:7458.
Scaioli E, Liverani E, Belluzz A, et al. The imbalance between n-6/n-3 polyunsaturated fatty acids and inflammatory bowel disease: a comprehensive review and future therapeutic perspectives. Int J Mol Sci. 2017;18:2619.
Watson H, Mitra S, Croden F, et al. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota. Gut. 2018;67:1974–1983.
Cushing K, Alvarado D, Ciorba M. Butyrate and mucosal inflammation: new scientific evidence supports clinical observation. Clin Transl Gastroenterol. 2015;6:e108.
De Wit N, Derrien M, Bosch-Vermeulen H, et al. Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine. Am J Physiol Gastrointest Liver Physiol. 2012;303:G589–G599.
Hessel S, Eichinger A, Isken A, et al. CMO1 deficiency abolishes vitamin A production from β-carotene and alters lipid metabolism in mice. J Biol Chem. 2007;282:33553–33561.
Paton CM, Ntambi JM. Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab. 2009;297:E28–E37.
Jenkins TC, Wallace RJ, Moate PJ, et al. Board-invited review: recent advances in biohydrogenation of unsaturated fatty acids within the rumen microbial ecosystem. J Anim Sci. 2008;86:397–412.
Yamada S, Kamada N, Amiya T, et al. Gut microbiota-mediated generation of saturated fatty acids elicits inflammation in the liver in murine high-fat diet-induced steatohepatitis. Gastroenterology. 2017;17:136.
Kim Y, Hirai S, Goto T. Potent PPARa activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice. PLoS ONE. 2012;7:e31317.
Kishino S, Takeuchi M, Park SB, et al. Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition. PNAS. 2013;110:17808–17813.
Ritze Y, Bárdos G, Claus A, et al. Lactobacillus rhamnosus GG protects against non -alcoholic fatty Liver Disease in Mice. PLoS One. 2014;9:e80169.
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Shama, S., Liu, W. Omega-3 Fatty Acids and Gut Microbiota: A Reciprocal Interaction in Nonalcoholic Fatty Liver Disease. Dig Dis Sci 65, 906–910 (2020). https://doi.org/10.1007/s10620-020-06117-5
- Gut microbiota
- n-3/n-6 PUFA