Top

Reviews in Endocrine and Metabolic Disorders

Published in:

Open Access 01-12-2019 | Dyslipidemia

Dietary lipids, gut microbiota and lipid metabolism

Authors: Marc Schoeler, Robert Caesar

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 4/2019

Abstract

The gut microbiota is a central regulator of host metabolism. The composition and function of the gut microbiota is dynamic and affected by diet properties such as the amount and composition of lipids. Hence, dietary lipids may influence host physiology through interaction with the gut microbiota. Lipids affect the gut microbiota both as substrates for bacterial metabolic processes, and by inhibiting bacterial growth by toxic influence. The gut microbiota has been shown to affect lipid metabolism and lipid levels in blood and tissues, both in mice and humans. Furthermore, diseases linked to dyslipidemia, such as non-alcoholic liver disease and atherosclerosis, are associated with changes in gut microbiota profile. The influence of the gut microbiota on host lipid metabolism may be mediated through metabolites produced by the gut microbiota such as short-chain fatty acids, secondary bile acids and trimethylamine and by pro-inflammatory bacterially derived factors such as lipopolysaccharide. Here we will review the association between gut microbiota, dietary lipids and lipid metabolism

Sonnenburg JL, Backhed F. Diet-microbiota interactions as moderators of human metabolism. Nature. 2016;535(7610):56–64. https://doi.org/10.1038/nature18846.CrossRefPubMedPubMedCentral

Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):913-6.e7. doi:10.1053/j.gastro.2012.06.031.CrossRef

Koutnikova H, Genser B, Monteiro-Sepulveda M, Faurie J-M, Rizkalla S, Schrezenmeir J et al. Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials. 2019;9(3):e017995. doi:10.1136/bmjopen-2017-017995 %J BMJ Open.

Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214. https://doi.org/10.1126/science.1241214.CrossRefPubMed

Zhou D, Pan Q, Shen F, Cao HX, Ding WJ, Chen YW, et al. Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci Rep. 2017;7(1):1529. https://doi.org/10.1038/s41598-017-01751-y.CrossRefPubMedPubMedCentral

Tremaroli V, Karlsson F, Werling M, Stahlman M, Kovatcheva-Datchary P, Olbers T, et al. Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation. Cell Metab. 2015;22(2):228–38. https://doi.org/10.1016/j.cmet.2015.07.009.CrossRefPubMedPubMedCentral

Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–31. https://doi.org/10.1038/nature05414.CrossRefPubMed

Katsiki N, Mikhailidis DP, Mantzoros CS. Non-alcoholic fatty liver disease and dyslipidemia: An update. Metabolism: clinical and experimental. 2016;65(8):1109–23. https://doi.org/10.1016/j.metabol.2016.05.003.CrossRef

Grundy SM. Metabolic syndrome update. Trends Cardiovasc Med. 2016;26(4):364–73. https://doi.org/10.1016/j.tcm.2015.10.004.CrossRefPubMed

10.

Caesar R, Tremaroli V, Kovatcheva-Datchary P, Cani Patrice D, Bäckhed F. Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling. Cell Metabolism. 2015;22(4):658–68. https://doi.org/10.1016/j.cmet.2015.07.026.CrossRefPubMedPubMedCentral

11.

Just S, Mondot S, Ecker J, Wegner K, Rath E, Gau L, et al. The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism. Microbiome. 2018;6(1):134. https://doi.org/10.1186/s40168-018-0510-8.CrossRefPubMedPubMedCentral

12.

Lam YY, Ha CW, Hoffmann JM, Oscarsson J, Dinudom A, Mather TJ, et al. Effects of dietary fat profile on gut permeability and microbiota and their relationships with metabolic changes in mice. Obesity (Silver Spring). 2015;23(7):1429–39. https://doi.org/10.1002/oby.21122.CrossRef

13.

Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansionand colitis in Il10-/- mice. Nature. 2012;487(7405):104-8. https://doi.org/10.1038/nature11225.CrossRef

14.

Jackman JA, Yoon BK, Li D, Cho NJ. Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides. Molecules (Basel, Switzerland). 2016;21(3):305. https://doi.org/10.3390/molecules21030305.CrossRef

15.

Shilling M, Matt L, Rubin E, Visitacion MP, Haller NA, Grey SF, et al. Antimicrobial effects of virgin coconut oil and its medium-chain fatty acids on Clostridium difficile. Journal of medicinal food. 2013;16(12):1079–85. https://doi.org/10.1089/jmf.2012.0303.CrossRefPubMed

16.

Sheu CW, Freese E. Effects of fatty acids on growth and envelope proteins of Bacillus subtilis. J Bacteriol. 1972;111(2):516–24.PubMedPubMedCentral

17.

Zheng CJ, Yoo JS, Lee TG, Cho HY, Kim YH, Kim WG. Fatty acid synthesis is a target for antibacterial activity of unsaturated fatty acids. FEBS letters. 2005;579(23):5157–62. https://doi.org/10.1016/j.febslet.2005.08.028.CrossRefPubMed

18.

Chen P, Torralba M, Tan J, Embree M, Zengler K, Starkel P, et al. Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice. Gastroenterology. 2015;148(1):203–14.e16. https://doi.org/10.1053/j.gastro.2014.09.014.CrossRefPubMed

19.

Kim YJ. Liu RH. Increase of Conjugated Linoleic Acid Content in Milk by Fermentation with Lactic Acid Bacteria. 2002;67(5):1731–7. https://doi.org/10.1111/j.1365-2621.2002.tb08714.x.CrossRef

20.

Ogawa J, Kishino S, Ando A, Sugimoto S, Mihara K, Shimizu S. Production of conjugated fatty acids by lactic acid bacteria. Journal of bioscience and bioengineering. 2005;100(4):355–64. https://doi.org/10.1263/jbb.100.355.CrossRefPubMed

21.

Brown JM, McIntosh MK. Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity. J Nutr. 2003;133(10):3041–6. https://doi.org/10.1093/jn/133.10.3041.CrossRefPubMedPubMedCentral

22.

Wargent E, Sennitt MV, Stocker C, Mayes AE, Brown L, O'Dowd J, et al. Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation. Lipids Health Dis. 2005;4:3. https://doi.org/10.1186/1476-511x-4-3.CrossRefPubMedPubMedCentral

23.

Granlund L, Juvet LK, Pedersen JI, Nebb HI. Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARgamma modulator. J Lipid Res. 2003;44(8):1441–52. https://doi.org/10.1194/jlr.M300120-JLR200.CrossRefPubMed

24.

Ecker J, Liebisch G, Patsch W, Schmitz G. The conjugated linoleic acid isomer trans-9,trans-11 is a dietary occurring agonist of liver X receptor alpha. Biochem Biophys Res Commun. 2009;388(4):660–6. https://doi.org/10.1016/j.bbrc.2009.08.048.CrossRefPubMed

25.

Coakley M, Ross RP, Nordgren M, Fitzgerald G, Devery R, Stanton C. Conjugated linoleic acid biosynthesis by human-derived Bifidobacterium species. Journal of applied microbiology. 2003;94(1):138–45.CrossRef

26.

Lee HY, Park JH, Seok SH, Baek MW, Kim DJ, Lee KE, et al. Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta. 2006;1761(7):736–44. https://doi.org/10.1016/j.bbalip.2006.05.007.CrossRefPubMed

27.

Miyamoto J, Mizukure T, Park SB, Kishino S, Kimura I, Hirano K, et al. A gut microbial metabolite of linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, ameliorates intestinal epithelial barrier impairment partially via GPR40-MEK-ERK pathway. J Biol Chem. 2015;290(5):2902–18. https://doi.org/10.1074/jbc.M114.610733.CrossRefPubMed

28.

Goto T, Kim YI, Furuzono T, Takahashi N, Yamakuni K, Yang HE, et al. 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, potently activates PPARgamma and stimulates adipogenesis. Biochem Biophys Res Commun. 2015;459(4):597–603. https://doi.org/10.1016/j.bbrc.2015.02.154.CrossRefPubMed

29.

Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007;104(3):979–84. https://doi.org/10.1073/pnas.0605374104.CrossRefPubMedPubMedCentral

30.

Velagapudi VR, Hezaveh R, Reigstad CS, Gopalacharyulu P, Yetukuri L, Islam S, et al. The gut microbiota modulates host energy and lipid metabolism in mice. Journal of Lipid Research. 2010;51(5):1101–12. https://doi.org/10.1194/jlr.M002774.CrossRefPubMedPubMedCentral

31.

Rabot S, Membrez M, Bruneau A, Gerard P, Harach T, Moser M, et al. Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J. 2010:4948–59. https://doi.org/10.1096/fj.10-164921.CrossRef

32.

Kindt A, Liebisch G, Clavel T, Haller D, Hormannsperger G, Yoon H, et al. The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice. Nat Commun. 2018;9(1):3760. https://doi.org/10.1038/s41467-018-05767-4.CrossRefPubMedPubMedCentral

33.

Schedin-Weiss S, Caesar I, Winblad B, Blom H, Tjernberg LO. Super-resolution microscopy reveals gamma-secretase at both sides of the neuronal synapse. Acta Neuropathol Commun. 2016;4:29. https://doi.org/10.1186/s40478-016-0296-5.CrossRefPubMedPubMedCentral

34.

Yoo SR, Kim YJ, Park DY, Jung UJ, Jeon SM, Ahn YT, et al. Probiotics L. plantarum and L. curvatus in combination alter hepatic lipid metabolism and suppress diet-induced obesity. Obesity (Silver Spring). 2013;21(12):2571–8. https://doi.org/10.1002/oby.20428.CrossRef

35.

An HM, Park SY, Lee DK, Kim JR, Cha MK. Lee SW et al. Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats. Lipids Health Dis. 2011;10:116. https://doi.org/10.1186/1476-511x-10-116.CrossRefPubMed

36.

Castaner O, Goday A, Park YM, Lee SH, Magkos F, Shiow STE, et al. The Gut Microbiome Profile in Obesity: A Systematic Review. Int J Endocrinol. 2018;2018:4095789. https://doi.org/10.1155/2018/4095789.CrossRefPubMedPubMedCentral

37.

Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500(7464):585–8. https://doi.org/10.1038/nature12480.CrossRefPubMed

38.

Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541–6. https://doi.org/10.1038/nature12506.CrossRefPubMed

39.

Fu J, Bonder MJ, Cenit MC, Tigchelaar EF, Maatman A, Dekens JA, et al. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids. Circulation research. 2015;117(9):817–24. https://doi.org/10.1161/circresaha.115.306807.CrossRefPubMedPubMedCentral

40.

Koren O, Spor A, Felin J, Fak F, Stombaugh J, Tremaroli V, et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4592–8. https://doi.org/10.1073/pnas.1011383107.CrossRefPubMed

41.

Karlsson FH, Fak F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun. 2012;3:1245. https://doi.org/10.1038/ncomms2266.CrossRefPubMedPubMedCentral

42.

Emoto T, Yamashita T, Sasaki N, Hirota Y, Hayashi T, So A, et al. Analysis of Gut Microbiota in Coronary Artery Disease Patients: a Possible Link between Gut Microbiota and Coronary Artery Disease. J Atheroscler Thromb. 2016;23(8):908–21. https://doi.org/10.5551/jat.32672.CrossRefPubMed

43.

Da Silva HE, Teterina A, Comelli EM, Taibi A, Arendt BM, Fischer SE, et al. Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance. Sci Rep. 2018;8(1):1466. https://doi.org/10.1038/s41598-018-19753-9.CrossRefPubMedPubMedCentral

44.

Michail S, Lin M, Frey MR, Fanter R, Paliy O, Hilbush B, et al. Altered gut microbial energy and metabolism in children with non-alcoholic fatty liver disease. FEMS microbiology ecology. 2015;91(2):1–9. https://doi.org/10.1093/femsec/fiu002.CrossRefPubMed

45.

Del Chierico F, Nobili V, Vernocchi P, Russo A, Stefanis C, Gnani D, et al. Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach. Hepatology (Baltimore, Md). 2017;65(2):451–64. https://doi.org/10.1002/hep.28572.CrossRef

46.

Hoyles L, Fernández-Real J-M, Federici M, Serino M, Abbott J, Charpentier J, et al. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nature Medicine. 2018;24(7):1070–80. https://doi.org/10.1038/s41591-018-0061-3.CrossRefPubMedPubMedCentral

47.

Boursier J, Mueller O, Barret M, Machado M, Fizanne L, Araujo-Perez F, et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology (Baltimore, Md). 2016;63(3):764–75. https://doi.org/10.1002/hep.28356.CrossRef

48.

Loomba R, Seguritan V, Li W, Long T, Klitgord N, Bhatt A, et al. Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. Cell Metab. 2017;25(5):1054–62.e5. https://doi.org/10.1016/j.cmet.2017.04.001.CrossRefPubMedPubMedCentral

49.

Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987;28(10):1221–7. https://doi.org/10.1136/gut.28.10.1221.CrossRefPubMedPubMedCentral

50.

Bergman EN. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiological reviews. 1990;70(2):567–90. https://doi.org/10.1152/physrev.1990.70.2.567.CrossRefPubMed

51.

den Besten G, Lange K, Havinga R, van Dijk TH, Gerding A, van Eunen K, et al. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am J Physiol Gastrointest Liver Physiol. 2013;305(12):G900–10. https://doi.org/10.1152/ajpgi.00265.2013.CrossRef

52.

Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61(2):364–71. https://doi.org/10.2337/db11-1019.CrossRefPubMedPubMedCentral

53.

Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013;4:1829. https://doi.org/10.1038/ncomms2852.CrossRefPubMedPubMedCentral

54.

Ge H, Li X, Weiszmann J, Wang P, Baribault H, Chen JL, et al. Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology. 2008;149(9):4519–26. https://doi.org/10.1210/en.2008-0059.CrossRefPubMed

55.

McNelis JC, Lee YS, Mayoral R, van der Kant R, Johnson AM, Wollam J, et al. GPR43 Potentiates beta-Cell Function in Obesity. Diabetes. 2015;64(9):3203–17. https://doi.org/10.2337/db14-1938.CrossRefPubMedPubMedCentral

56.

Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG, Zac-Varghese SE, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015;64(11):1744–54. https://doi.org/10.1136/gutjnl-2014-307913.CrossRefPubMed

57.

Robertson MD, Bickerton AS, Dennis AL, Vidal H, Frayn KN. Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am J Clin Nutr. 2005;82(3):559–67. https://doi.org/10.1093/ajcn.82.3.559.CrossRefPubMed

58.

Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A. 2008;105(43):16767–72. https://doi.org/10.1073/pnas.0808567105.CrossRefPubMedPubMedCentral

59.

Alex S, Lange K, Amolo T, Grinstead JS, Haakonsson AK, Szalowska E, et al. Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor gamma. Mol Cell Biol. 2013;33(7):1303–16. https://doi.org/10.1128/mcb.00858-12.CrossRefPubMedPubMedCentral

60.

Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58(7):1509–17. https://doi.org/10.2337/db08-1637.CrossRefPubMedPubMedCentral

61.

den Besten G, Bleeker A, Gerding A, van Eunen K, Havinga R, van Dijk TH, et al. Short-Chain Fatty Acids Protect Against High-Fat Diet-Induced Obesity via a PPARgamma-Dependent Switch From Lipogenesis to Fat Oxidation. Diabetes. 2015;64(7):2398–408. https://doi.org/10.2337/db14-1213.CrossRef

62.

Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016;165(6):1332–45. https://doi.org/10.1016/j.cell.2016.05.041.CrossRefPubMed

63.

Yamashita H, Fujisawa K, Ito E, Idei S, Kawaguchi N, Kimoto M, et al. Improvement of obesity and glucose tolerance by acetate in Type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Bioscience, biotechnology, and biochemistry. 2007;71(5):1236–43.CrossRef

64.

De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014;156(1-2):84–96. https://doi.org/10.1016/j.cell.2013.12.016.CrossRefPubMed

65.

Nicolucci AC, Hume MP, Martinez I, Mayengbam S, Walter J, Reimer RA. Prebiotics Reduce Body Fat and Alter Intestinal Microbiota in Children Who Are Overweight or With Obesity. Gastroenterology. 2017;153(3):711–22. https://doi.org/10.1053/j.gastro.2017.05.055.CrossRefPubMed

66.

Freeland KR, Wolever TM. Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha. Br J Nutr. 2010;103(3):460–6. https://doi.org/10.1017/s0007114509991863.CrossRefPubMed

67.

Wahlstrom A, Sayin SI, Marschall HU, Backhed F. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. Cell Metab. 2016;24(1):41–50. https://doi.org/10.1016/j.cmet.2016.05.005.CrossRefPubMed

68.

Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999;284(5418):1365–8. https://doi.org/10.1126/science.284.5418.1365.CrossRefPubMed

69.

Mueller M, Thorell A, Claudel T, Jha P, Koefeler H, Lackner C, et al. Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity. J Hepatol. 2015;62(6):1398–404. https://doi.org/10.1016/j.jhep.2014.12.034.CrossRefPubMedPubMedCentral

70.

Sayin Sama I, Wahlström A, Felin J, Jäntti S, Marschall H-U, Bamberg K, et al. Gut Microbiota Regulates Bile Acid Metabolism by Reducing the Levels of Tauro-beta-muricholic Acid, a Naturally Occurring FXR Antagonist. Cell Metabolism. 2013;17(2):225–35. https://doi.org/10.1016/j.cmet.2013.01.003.CrossRefPubMed

71.

Kalaany NY, Mangelsdorf DJ. LXRS and FXR: the yin and yang of cholesterol and fat metabolism. Annual review of physiology. 2006;68:159–91. https://doi.org/10.1146/annurev.physiol.68.033104.152158.CrossRefPubMed

72.

Parseus A, Sommer N, Sommer F, Caesar R, Molinaro A, Stahlman M, et al. Microbiota-induced obesity requires farnesoid X receptor. Gut. 2017;66(3):429–37. https://doi.org/10.1136/gutjnl-2015-310283.CrossRefPubMed

73.

Fang S, Suh JM, Reilly SM, Yu E, Osborn O, Lackey D, et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med. 2015;21(2):159–65. https://doi.org/10.1038/nm.3760.CrossRefPubMedPubMedCentral

74.

Ma K, Saha PK, Chan L, Moore DD. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest. 2006;116(4):1102–9. https://doi.org/10.1172/jci25604.CrossRefPubMedPubMedCentral

75.

Jiang C, Xie C, Lv Y, Li J, Krausz KW, Shi J, et al. Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. Nat Commun. 2015;6:10166. https://doi.org/10.1038/ncomms10166.CrossRefPubMedPubMedCentral

76.

Li F, Jiang C, Krausz KW, Li Y, Albert I, Hao H, et al. Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity. Nat Commun. 2013;4:2384. https://doi.org/10.1038/ncomms3384.CrossRefPubMedPubMedCentral

77.

Jiang C, Xie C, Li F, Zhang L, Nichols RG, Krausz KW, et al. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J Clin Invest. 2015;125(1):386–402. https://doi.org/10.1172/jci76738.CrossRefPubMed

78.

Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484–9. https://doi.org/10.1038/nature04330.CrossRefPubMed

79.

Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10(3):167–77. https://doi.org/10.1016/j.cmet.2009.08.001.CrossRefPubMedPubMedCentral

80.

Broeders EP, Nascimento EB, Havekes B, Brans B, Roumans KH, Tailleux A, et al. The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity. Cell Metab. 2015;22(3):418–26. https://doi.org/10.1016/j.cmet.2015.07.002.CrossRefPubMed

81.

Mouzaki M, Wang AY, Bandsma R, Comelli EM, Arendt BM, Zhang L, et al. Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease. PLoS One. 2016;11(5):e0151829. https://doi.org/10.1371/journal.pone.0151829.CrossRefPubMedPubMedCentral

82.

Alisi A, Ceccarelli S, Panera N, Prono F, Petrini S, De Stefanis C, et al. Association between Serum Atypical Fibroblast Growth Factors 21 and 19 and Pediatric Nonalcoholic Fatty Liver Disease. PLoS One. 2013;8(6):e67160. https://doi.org/10.1371/journal.pone.0067160.CrossRefPubMedPubMedCentral

83.

Wojcik M, Janus D, Dolezal-Oltarzewska K, Kalicka-Kasperczyk A, Poplawska K, Drozdz D, et al. A decrease in fasting FGF19 levels is associated with the development of non-alcoholic fatty liver disease in obese adolescents. Journal of pediatric endocrinology & metabolism : JPEM. 2012;25(11-12):1089–93. https://doi.org/10.1515/jpem-2012-0253.CrossRef

84.

Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology (Baltimore, Md). 2004;39(3):770–8. https://doi.org/10.1002/hep.20092.CrossRef

85.

Leuschner UF, Lindenthal B, Herrmann G, Arnold JC, Rossle M, Cordes HJ, et al. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial. Hepatology (Baltimore, Md). 2010;52(2):472–9. https://doi.org/10.1002/hep.23727.CrossRef

86.

Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet (London, England). 2015;385(9972):956–65. https://doi.org/10.1016/s0140-6736(14)61933-4.CrossRef

87.

Harrison SA, Rinella ME, Abdelmalek MF, Trotter JF, Paredes AH, Arnold HL, et al. NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet (London, England). 2018;391(10126):1174–85. https://doi.org/10.1016/s0140-6736(18)30474-4.CrossRef

88.

Erridge C, Attina T, Spickett CM, Webb DJ. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr. 2007;86(5):1286–92. https://doi.org/10.1093/ajcn/86.5.1286.CrossRefPubMed

89.

Velasquez OR, Henninger K, Fowler M, Tso P, Crissinger KD. Oleic acid-induced mucosal injury in developing piglet intestine. Am J Physiol. 1993;264(3 Pt 1):G576–82. https://doi.org/10.1152/ajpgi.1993.264.3.G576.CrossRefPubMed

90.

Levels JH, Abraham PR, van den Ende A, van Deventer SJ. Distribution and kinetics of lipoprotein-bound endotoxin. Infect Immun. 2001;69(5):2821–8. https://doi.org/10.1128/IAI.69.5.2821-2828.2001.CrossRefPubMedPubMedCentral

91.

Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761–72. https://doi.org/10.2337/db06-1491.CrossRefPubMed

92.

Pirlich M, Norman K, Lochs H, Bauditz J. Role of intestinal function in cachexia. Curr Opin Clin Nutr Metab Care. 2006;9(5):603–6. https://doi.org/10.1097/01.mco.0000241671.09676.d8.CrossRefPubMed

93.

Manco M, Putignani L, Bottazzo GF. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev. 2010;31(6):817–44. https://doi.org/10.1210/er.2009-0030.CrossRefPubMed

94.

Read TE, Harris HW, Grunfeld C, Feingold KR, Kane JP, Rapp JH. The protective effect of serum lipoproteins against bacterial lipopolysaccharide. Eur Heart J. 1993;14 Suppl K:125-9.

95.

Eichbaum EB, Harris HW, Kane JP, Rapp JH. Chylomicrons can inhibit endotoxin activity in vitro. J Surg Res. 1991;51(5):413–6.CrossRef

96.

Harris HW, Grunfeld C, Feingold KR, Rapp JH. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice. J Clin Invest. 1990;86(3):696–702. https://doi.org/10.1172/JCI114765.CrossRefPubMedPubMedCentral

97.

Pajkrt D, Doran JE, Koster F, Lerch PG, Arnet B, van der Poll T, et al. Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. J Exp Med. 1996;184(5):1601–8. https://doi.org/10.1084/jem.184.5.1601.CrossRefPubMed

98.

Feingold KR, Funk JL, Moser AH, Shigenaga JK, Rapp JH, Grunfeld C. Role for circulating lipoproteins in protection from endotoxin toxicity. Infect Immun. 1995;63(5):2041–6.PubMedPubMedCentral

99.

Lehr HA, Sagban TA, Ihling C, Zahringer U, Hungerer KD, Blumrich M, et al. Immunopathogenesis of atherosclerosis: endotoxin accelerates atherosclerosis in rabbits on hypercholesterolemic diet. Circulation. 2001;104(8):914–20. https://doi.org/10.1161/hc3401.093153.CrossRefPubMed

100.

Michelsen KS, Wong MH, Shah PK, Zhang W, Yano J, Doherty TM, et al. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc Natl Acad Sci U S A. 2004;101(29):10679–84. https://doi.org/10.1073/pnas.0403249101.CrossRefPubMedPubMedCentral

101.

Kiechl S, Egger G, Mayr M, Wiedermann CJ, Bonora E, Oberhollenzer F, et al. Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. Circulation. 2001;103(8):1064–70. https://doi.org/10.1161/01.cir.103.8.1064.CrossRefPubMed

102.

McIntyre CW, Harrison LE, Eldehni MT, Jefferies HJ, Szeto CC, John SG, et al. Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. Clinical journal of the American Society of Nephrology : CJASN. 2011;6(1):133–41. https://doi.org/10.2215/cjn.04610510.CrossRefPubMed

103.

Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000;25(2):187–91. https://doi.org/10.1038/76048.CrossRefPubMed

104.

Kiechl S, Lorenz E, Reindl M, Wiedermann CJ, Oberhollenzer F, Bonora E, et al. Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med. 2002;347(3):185–92. https://doi.org/10.1056/NEJMoa012673.CrossRefPubMed

105.

Ameziane N, Beillat T, Verpillat P, Chollet-Martin S, Aumont MC, Seknadji P, et al. Association of the Toll-like receptor 4 gene Asp299Gly polymorphism with acute coronary events. Arterioscler Thromb Vasc Biol. 2003;23(12):e61–4. https://doi.org/10.1161/01.ATV.0000101191.92392.1D.CrossRefPubMed

106.

Mao J-W, Tang H-Y, Zhao T, Tan X-Y, Bi J, Wang B-Y, et al. Intestinal mucosal barrier dysfunction participates in the progress of nonalcoholic fatty liver disease. Int J Clin Exp Pathol. 2015;8(4):3648–58.PubMedPubMedCentral

107.

Mencin A, Kluwe J, Schwabe RF. Toll-like receptors as targets in chronic liver diseases. Gut. 2009;58(5):704–20. https://doi.org/10.1136/gut.2008.156307.CrossRefPubMedPubMedCentral

108.

Federico A, Dallio M, Godos J, Loguercio C, Salomone F. Targeting gut-liver axis for the treatment of nonalcoholic steatohepatitis: translational and clinical evidence. Translational research : the journal of laboratory and clinical medicine. 2016;167(1):116–24. https://doi.org/10.1016/j.trsl.2015.08.002.CrossRef

109.

Everard A, Geurts L, Caesar R, Van Hul M, Matamoros S, Duparc T, et al. Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status. Nat Commun. 2014;5. https://doi.org/10.1038/ncomms6648.

110.

111.

Friedman SL. Liver fibrosis in 2012: Convergent pathways that cause hepatic fibrosis in NASH. Nat Rev Gastroenterol Hepatol. 2013;10(2):71–2. https://doi.org/10.1038/nrgastro.2012.256.CrossRefPubMed

112.

Wree A, McGeough MD, Pena CA, Schlattjan M, Li H, Inzaugarat ME, et al. NLRP3 inflammasome activation is required for fibrosis development in NAFLD. Journal of molecular medicine (Berlin, Germany). 2014;92(10):1069–82. https://doi.org/10.1007/s00109-014-1170-1.CrossRef

113.

Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology (Baltimore, Md). 2009;49(6):1877–87. https://doi.org/10.1002/hep.22848.CrossRef

114.

Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575–84. https://doi.org/10.1056/NEJMoa1109400.CrossRefPubMedPubMedCentral

115.

Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576–85. https://doi.org/10.1038/nm.3145.CrossRefPubMedPubMedCentral

116.

Wang Z, Tang WH, Buffa JA, Fu X, Britt EB, Koeth RA, et al. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J. 2014;35(14):904–10. https://doi.org/10.1093/eurheartj/ehu002.CrossRefPubMedPubMedCentral

117.

Bennett BJ, Davis RC, Civelek M, Orozco L, Wu J, Qi H, et al. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains. PLoS genetics. 2015;11(12):e1005711. https://doi.org/10.1371/journal.pgen.1005711.CrossRefPubMedPubMedCentral

118.

Gregory JC, Buffa JA, Org E, Wang Z, Levison BS, Zhu W, et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290(9):5647–60. https://doi.org/10.1074/jbc.M114.618249.CrossRefPubMed

119.

Shih DM, Wang Z, Lee R, Meng Y, Che N, Charugundla S, et al. Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis. J Lipid Res. 2015;56(1):22–37. https://doi.org/10.1194/jlr.M051680.CrossRefPubMedPubMedCentral

120.

Miao J, Ling AV, Manthena PV, Gearing ME, Graham MJ, Crooke RM, et al. Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis. Nat Commun. 2015;6:6498. https://doi.org/10.1038/ncomms7498.CrossRefPubMedPubMedCentral

121.

Bennett BJ, de Aguiar Vallim TQ, Wang Z, Shih DM, Meng Y, Gregory J, et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 2013;17(1):49–60. https://doi.org/10.1016/j.cmet.2012.12.011.CrossRefPubMedPubMedCentral

122.

Seldin MM, Meng Y, Qi H, Zhu W, Wang Z, Hazen SL, et al. Trimethylamine N-Oxide Promotes Vascular Inflammation Through Signaling of Mitogen-Activated Protein Kinase and Nuclear Factor-kappaB. Journal of the American Heart Association. 2016;5(2). https://doi.org/10.1161/jaha.115.002767.

123.

Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, et al. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell. 2016;165(1):111–24. https://doi.org/10.1016/j.cell.2016.02.011.CrossRefPubMedPubMedCentral

124.

Mente A, Chalcraft K, Ak H, Davis AD, Lonn E, Miller R, et al. The Relationship Between Trimethylamine-N-Oxide and Prevalent Cardiovascular Disease in a Multiethnic Population Living in Canada. The Canadian journal of cardiology. 2015;31(9):1189–94. https://doi.org/10.1016/j.cjca.2015.06.016.CrossRefPubMed

125.

Troseid M, Ueland T, Hov JR, Svardal A, Gregersen I, Dahl CP, et al. Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J Intern Med. 2015;277(6):717–26. https://doi.org/10.1111/joim.12328.CrossRefPubMed

126.

Lindskog Jonsson A, Caesar R, Akrami R, Reinhardt C, Fak Hallenius F, Boren J, et al. Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe(-/-) Mice. Arterioscler Thromb Vasc Biol. 2018;38(10):2318–26. https://doi.org/10.1161/atvbaha.118.311233.CrossRefPubMedPubMedCentral

127.

Collins HL, Drazul-Schrader D, Sulpizio AC, Koster PD, Williamson Y, Adelman SJ, et al. L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE(-/-) transgenic mice expressing CETP. Atherosclerosis. 2016;244:29–37. https://doi.org/10.1016/j.atherosclerosis.2015.10.108.CrossRefPubMed

128.

Shimizu M, Hashiguchi M, Shiga T, Tamura HO, Mochizuki M. Meta-Analysis: Effects of Probiotic Supplementation on Lipid Profiles in Normal to Mildly Hypercholesterolemic Individuals. PLoS One. 2015;10(10):e0139795. https://doi.org/10.1371/journal.pone.0139795.CrossRefPubMedPubMedCentral

129.

Wu Y, Zhang Q, Ren Y, Ruan Z. Effect of probiotic Lactobacillus on lipid profile: A systematic review and meta-analysis of randomized, controlled trials. PLoS One. 2017;12(6):e0178868. https://doi.org/10.1371/journal.pone.0178868.CrossRefPubMedPubMedCentral

130.

Ruscica M, Pavanello C, Gandini S, Macchi C, Botta M, Dall'Orto D, et al. Nutraceutical approach for the management of cardiovascular risk - a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study. Nutr J. 2019;18(1):13. https://doi.org/10.1186/s12937-019-0438-2.CrossRefPubMedPubMedCentral

131.

Loman BR, Hernandez-Saavedra D, An R, Rector RS. Prebiotic and probiotic treatment of nonalcoholic fatty liver disease: a systematic review and meta-analysis. Nutr Rev. 2018;76(11):822–39. https://doi.org/10.1093/nutrit/nuy031.CrossRefPubMed

132.

Liu Y, Song X, Zhou H, Zhou X, Xia Y, Dong X, et al. Gut Microbiome Associates With Lipid-Lowering Effect of Rosuvastatin in Vivo. Front Microbiol. 2018;9:530. https://doi.org/10.3389/fmicb.2018.00530.CrossRefPubMedPubMedCentral

133.

Nolan JA, Skuse P, Govindarajan K, Patterson E, Konstantinidou N, Casey PG, et al. The influence of rosuvastatin on the gastrointestinal microbiota and host gene expression profiles. Am J Physiol Gastrointest Liver Physiol. 2017;312(5):G488–G97. https://doi.org/10.1152/ajpgi.00149.2016.CrossRefPubMed

134.

Caparros-Martin JA, Lareu RR, Ramsay JP, Peplies J, Reen FJ, Headlam HA, et al. Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism. Microbiome. 2017;5(1):95. https://doi.org/10.1186/s40168-017-0312-4.CrossRefPubMedPubMedCentral

135.

Portugal LR, Goncalves JL, Fernandes LR, Silva HP, Arantes RM, Nicoli JR, et al. Effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and on atherogenesis in apolipoprotein E knock-out mice. Braz J Med Biol Res. 2006;39(5):629–35. https://doi.org/10.1590/s0100-879x2006000500010.CrossRefPubMed

136.

Fak F, Backhed F. Lactobacillus reuteri prevents diet-induced obesity, but not atherosclerosis, in a strain dependent fashion in Apoe-/- mice. PLoS One. 2012;7(10):e46837. https://doi.org/10.1371/journal.pone.0046837.CrossRefPubMedPubMedCentral

137.

Li J, Lin S, Vanhoutte PM, Woo CW, Xu A. Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe-/- Mice. Circulation. 2016;133(24):2434–46. https://doi.org/10.1161/CIRCULATIONAHA.115.019645.CrossRefPubMed

138.

Johnson AJ, Vangay P, Al-Ghalith GA, Hillmann BM, Ward TL, Shields-Cutler RR, et al. Daily Sampling Reveals Personalized Diet-Microbiome Associations in Humans. Cell Host Microbe. 2019;25(6):789–802.e5. https://doi.org/10.1016/j.chom.2019.05.005.CrossRefPubMed

139.

Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015;163(5):1079–94. https://doi.org/10.1016/j.cell.2015.11.001.CrossRefPubMed

Title: Dietary lipids, gut microbiota and lipid metabolism
Authors: Marc Schoeler
Robert Caesar
Publication date: 01-12-2019
Publisher: Springer US
Keywords: Dyslipidemia
Arterial Occlusive Disease
Respiratory Microbiota
Published in: Reviews in Endocrine and Metabolic Disorders / Issue 4/2019
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI: https://doi.org/10.1007/s11154-019-09512-0

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Dietary lipids, gut microbiota and lipid metabolism

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2019

Gut microbiome and cardiometabolic risk

Oral microbiota-induced periodontitis: a new risk factor of metabolic diseases

Gut microbiota-derived succinate: Friend or foe in human metabolic diseases?

Microbiota impacts on chronic inflammation and metabolic syndrome - related cognitive dysfunction

Keto microbiota: A powerful contributor to host disease recovery

The gut microbiome and heart failure: A better gut for a better heart

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page